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Sample records for lung disability trust

  1. Renewable Energy Trust Fund

    Broader source: Energy.gov [DOE]

    The renewable energy fund, known as the Massachusetts Renewable Energy Trust Fund, is supported by a non-bypassable surcharge of $0.0005 per kilowatt-hour (0.5 mill/kWh), imposed on customers of...

  2. Efficiency Maine Trust

    Broader source: Energy.gov [DOE]

    In 2009, the Act Regarding Maine's Energy Future (Public Law 372) established a new entity, the Efficiency Maine Trust, which became responsible for Maine's energy efficiency and renewable energy...

  3. Carbon Trust | Open Energy Information

    Open Energy Info (EERE)

    Trust Jump to: navigation, search Name: Carbon Trust Place: London, Greater London, United Kingdom Zip: EC4A 3BF Sector: Carbon Product: London-based independent company funded by...

  4. Massachusetts Technology Collaborative - Renewable Energy Trust...

    Open Energy Info (EERE)

    - Renewable Energy Trust Jump to: navigation, search Logo: Massachusetts Technology Collaborative - Renewable Energy Trust Name: Massachusetts Technology Collaborative...

  5. Disability Plans

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Disability Plans Disability Plans A comprehensive benefits package with plan options for health care and retirement to take care of our employees today and tomorrow. Contact Benefits Office (505) 667-1806 Email Disability Plans The Lab offers employees both Short-term and Supplemental Disability plans through The Hartford. These income protection plans will pay a percentage of your salary when you are unable to work due to illness or injury. Resources Defined Benefit Eligibility Disability

  6. Energy Saving Trust EST | Open Energy Information

    Open Energy Info (EERE)

    Trust EST Jump to: navigation, search Name: Energy Saving Trust (EST) Place: London, United Kingdom Zip: SW1H 9BP Sector: Carbon Product: The Energy Saving Trust's goal is to...

  7. Carbon Trust Enterprises Limited | Open Energy Information

    Open Energy Info (EERE)

    Enterprises Limited Jump to: navigation, search Name: Carbon Trust Enterprises Limited Place: London, United Kingdom Zip: WC2A 2AZ Sector: Carbon Product: Carbon Trust Enterprises...

  8. Standard Steam Trust LLC | Open Energy Information

    Open Energy Info (EERE)

    (Redirected from Standard Steam Trust) Jump to: navigation, search Name: Standard Steam Trust LLC Place: Denver, Colorado Sector: Geothermal energy Product: Subsidiary of...

  9. Environmental Resources Trust Inc | Open Energy Information

    Open Energy Info (EERE)

    Trust Inc Jump to: navigation, search Name: Environmental Resources Trust, Inc Place: Washington DC, Washington, DC Zip: 20006 Product: Non-profit organisation funded by...

  10. In Trust AG | Open Energy Information

    Open Energy Info (EERE)

    Trust AG Jump to: navigation, search Name: in-Trust AG Place: Regensburg, Bavaria, Germany Zip: 93047 Product: Germany-based investment company focused mainly on investing in...

  11. Disability Services

    Broader source: Energy.gov [DOE]

    There are an estimated 54 million Americans with disabilities. We see them at work, on the street, in our neighborhoods. They may be sitting next to you right now, but if the disability is not...

  12. Climate Trust | Open Energy Information

    Open Energy Info (EERE)

    Place: Portland, Oregon Zip: OR 97204 Product: The Climate Trust is a non-profit organization providing solutions to reduce GHG emissions Coordinates: 45.511795, -122.675629...

  13. Cryptographic Trust Management System Design Document

    SciTech Connect (OSTI)

    Edgar, Thomas W.; Clements, Samuel L.; Hadley, Mark D.; Maiden, Wendy M.; Manz, David O.; Zabriskie, Sean J.

    2010-08-04

    Deliverable for DOE NSTB Cryptographic Trust Management project. Design document to follow the Requirements document submitted in Sept 2009.

  14. Carbon Trust Investments Ltd | Open Energy Information

    Open Energy Info (EERE)

    Investments Ltd Jump to: navigation, search Name: Carbon Trust Investments Ltd Place: United Kingdom Sector: Carbon Product: UK-based venture capital investment division of The...

  15. Standard Steam Trust LLC | Open Energy Information

    Open Energy Info (EERE)

    Jump to: navigation, search Name: Standard Steam Trust LLC Place: Denver, Colorado Sector: Geothermal energy Product: Subsidiary of Denver-based geothermal project developer, Terra...

  16. Trust Anchor Fact Sheet.cdr

    Energy Savers [EERE]

    Trust Anchor Lifecycle Attack Protection Trust Anchor Lifecycle Attack Protection Cryptographically secure software providing independent testing, monitoring, and control of energy control system component operation Cryptographically secure software providing independent testing, monitoring, and control of energy control system component operation Cyber Security for Energy Delivery Systems Electricity Delivery & Energy Reliability Project Lead: Sandia National Laboratories The Concept The

  17. Colorado State Bank and Trust | Open Energy Information

    Open Energy Info (EERE)

    Bank and Trust Jump to: navigation, search Name: Colorado State Bank and Trust Place: Denver, Colorado Zip: 80202 Sector: Renewable Energy Product: Leasing and lending for...

  18. City of Pittsburgh Implementation Model: Green Initiatives Trust...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    City of Pittsburgh Implementation Model: Green Initiatives Trust Fund City of Pittsburgh implementation model, Green initiatives trust fund. Author: U. S. Department of Energy City ...

  19. Utah School and Institutional Trust Lands Administration | Open...

    Open Energy Info (EERE)

    School and Institutional Trust Lands Administration Jump to: navigation, search Logo: Utah School and Institutional Trust Lands Administration Name: Utah School and Institutional...

  20. Quercus Trust David Gelbaum Private investor | Open Energy Information

    Open Energy Info (EERE)

    Quercus Trust David Gelbaum Private investor Jump to: navigation, search Name: Quercus Trust David Gelbaum (Private investor) Place: Newport Beach, California Zip: 92660 Product:...

  1. Massachusetts Renewable Energy Trust MRET | Open Energy Information

    Open Energy Info (EERE)

    Trust MRET Jump to: navigation, search Name: Massachusetts Renewable Energy Trust (MRET) Place: Westborough, Massachusetts Zip: MA 01581 Sector: Renewable Energy Product: USD 150m...

  2. Oregon Wave Energy Trust OWET | Open Energy Information

    Open Energy Info (EERE)

    Wave Energy Trust OWET Jump to: navigation, search Name: Oregon Wave Energy Trust (OWET) Place: Portland, Oregon Zip: 97207 Product: String representation "The Oregon Wave ... rgy...

  3. Building Trust in GHG Inventories from the United States and...

    Open Energy Info (EERE)

    Trust in GHG Inventories from the United States and China Jump to: navigation, search Tool Summary LAUNCH TOOL Name: Counting the Gigatones: Building Trust in GHG Inventories from...

  4. DualTrust: A Trust Management Model for Swarm-Based Autonomic Computing Systems

    SciTech Connect (OSTI)

    Maiden, Wendy M.

    2010-05-01

    Trust management techniques must be adapted to the unique needs of the application architectures and problem domains to which they are applied. For autonomic computing systems that utilize mobile agents and ant colony algorithms for their sensor layer, certain characteristics of the mobile agent ant swarm -- their lightweight, ephemeral nature and indirect communication -- make this adaptation especially challenging. This thesis looks at the trust issues and opportunities in swarm-based autonomic computing systems and finds that by monitoring the trustworthiness of the autonomic managers rather than the swarming sensors, the trust management problem becomes much more scalable and still serves to protect the swarm. After analyzing the applicability of trust management research as it has been applied to architectures with similar characteristics, this thesis specifies the required characteristics for trust management mechanisms used to monitor the trustworthiness of entities in a swarm-based autonomic computing system and describes a trust model that meets these requirements.

  5. National Trust for Historic Preservation: America Saves! Energizing Main

    Energy Savers [EERE]

    Street Small Businesses | Department of Energy Trust for Historic Preservation: America Saves! Energizing Main Street Small Businesses National Trust for Historic Preservation: America Saves! Energizing Main Street Small Businesses National Trust for Historic Preservation: America Saves! Energizing Main Street Small Businesses Lead Performer: National Trust for Historic Preservation - Washington, DC Partners: - National Renewable Energy Laboratory - Golden, CO - Lend Lease - New York, NY -

  6. City of Pittsburgh Implementation Model: Green Initiatives Trust Fund

    Broader source: Energy.gov [DOE]

    City of Pittsburgh implementation model, Green initiatives trust fund. Author: U. S. Department of Energy

  7. Carbon Trust CECIC JV | Open Energy Information

    Open Energy Info (EERE)

    CECIC JV Jump to: navigation, search Name: Carbon Trust & CECIC JV Place: China Sector: Carbon Product: China-based JV innovator and transferrer of low carbon technology in China....

  8. Declaration Of Trust | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Declaration Of Trust Declaration Of Trust Our Bank Deposit Financial Assistance Program was developed for the purpose of strengthening and expanding the Nation's minority and women-owned small business enterprises. In order to classify as "minority" the institution's majority ownership must include African Americans, Hispanic Americans, Asian Americans, American Indians, Eskimos, Aleuts, and women. The minority institution must certify minority ownership with the Department of the

  9. Leasing State Trust Lands in Washington | Open Energy Information

    Open Energy Info (EERE)

    Leasing State Trust Lands in Washington Jump to: navigation, search OpenEI Reference LibraryAdd to library Legal Document- OtherOther: Leasing State Trust Lands in WashingtonLegal...

  10. PURE the Clean Planet Trust | Open Energy Information

    Open Energy Info (EERE)

    PURE the Clean Planet Trust Jump to: navigation, search Name: PURE the Clean Planet Trust Place: London, Greater London, United Kingdom Zip: EC2N 4AW Product: Pure (the Clean...

  11. Air Force Generic In-Kind Consideration Trust Agreement | Open...

    Open Energy Info (EERE)

    Trust Agreement Jump to: navigation, search OpenEI Reference LibraryAdd to library Legal Document- OtherOther: Air Force Generic In-Kind Consideration Trust AgreementLegal Abstract...

  12. Improving the trust in results of numerical simulations and scientific...

    Office of Scientific and Technical Information (OSTI)

    by (1) exploring the sources of trust loss; (2) reviewing the definitions of trust in ... These corruptions may produce results that deviate from the user-expected accuracy without ...

  13. Solar Trust of America LLC | Open Energy Information

    Open Energy Info (EERE)

    Trust of America LLC Jump to: navigation, search Name: Solar Trust of America LLC Place: Cleveland, Ohio Zip: 44122 Product: Ohio-based turnkey project developer of STEG plants in...

  14. Disability Employment | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Disability Employment Disability Employment DOE's Statement on Disability Hiring The U. S. Department of Energy is committed to fostering a culture of diversity. We recognize that individuals with disabilities are an untapped talent pool and possess skills and competencies that the Department needs to remain competitive. The Department of Energy (DOE) is fully committed to improving our efforts to employ Federal workers with disabilities and targeted disabilities through increased recruiting,

  15. Announcing the Clean Energy Trust Semifinalists | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Announcing the Clean Energy Trust Semifinalists Announcing the Clean Energy Trust Semifinalists January 24, 2012 - 6:54pm Addthis Matthew Loveless Matthew Loveless Data Integration Specialist, Office of Public Affairs On January 6th, the Clean Energy Trust announced the semifinalists for its inaugural student clean energy challenge. Semifinalists were chosen from more than 40 innovative clean energy business plans submitted from eight Midwestern states. The 16 semifinalist teams represent five

  16. Trust Anchor Lifecycle Attack Protection | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Trust Anchor Lifecycle Attack Protection Trust Anchor Lifecycle Attack Protection Cryptographically secure software providing independent testing, monitoring, and control of energy control system component operation PDF icon Trust Anchor Lifecycle Attack Protection More Documents & Publications Cybersecurity for Energy Delivery Systems 2010 Peer Review Presentations - Vulnerability and Intrusion Detection DOE/OE National SCADA Test Bed Fiscal Year 2009 Work Plan Report of the Cyber Security

  17. MAINE MULTIFAMILY BUILDING OWNERS TRUST IN EFFICIENCY | Department of

    Energy Savers [EERE]

    Energy MAINE MULTIFAMILY BUILDING OWNERS TRUST IN EFFICIENCY MAINE MULTIFAMILY BUILDING OWNERS TRUST IN EFFICIENCY MAINE MULTIFAMILY BUILDING OWNERS TRUST IN EFFICIENCY Nearly 70% of households in Maine rely on fuel oil as their primary energy source for home heating, more than any other state. Coupled with the state's long, cold winters, homeowners' dependence on oil renders them particularly vulnerable to fluctuating fuel costs. Especially for the state's aging multifamily housing

  18. American Disabilities Act

    Broader source: Energy.gov [DOE]

    The Americans with Disabilities Act prohibits private employers, state and local governments, employment agencies and labor unions from discriminating against qualified individuals with disabilities in job application procedures, hiring, firing, advancement, compensation, job training, and other terms, conditions, and privileges of employment.

  19. Colorado - Rights of Way on State Trust Lands - General Information...

    Open Energy Info (EERE)

    OpenEI Reference LibraryAdd to library PermittingRegulatory Guidance - Supplemental Material: Colorado - Rights of Way on State Trust Lands - General InformationPermitting...

  20. Credibility and trust in federal facility cleanups

    SciTech Connect (OSTI)

    Raynes, D.B.

    1995-12-01

    The most important indicator of a well-managed site cleanup effort may no longer be funding or scientific expertise. While support for federal facility cleanup has included appropriations of more than $10 billion annually, these expenditures alone are unlikely to assure progress toward environmental remediation. {open_quotes}Trust{close_quotes} is now overwhelmingly mentioned as a prerequisite for progress with site cleanup in DOE`s weapons complex. In part, federal budget deficits are forcing participants to focus on factors that build consensus and lead to cost-effective cleanup actions. In some cases, the stakeholders at cleanup sites are making efforts to work cooperatively with federal agencies. A report by 40 representatives of federal agencies, tribal and state governments, associations, and others developed recommendations to create a {open_quotes}new era of trust and consensus-building that allows all parties to get on with the job of cleaning up federal facilities in a manner that reflects the priorities and concerns of all stakeholders.{close_quotes} Changes are underway affecting how federal agencies work with federal and state regulators reflecting this concept of shared responsibility for conducting cleanup. This paper addresses these changes and provides examples of the successes and failures underway.

  1. Cyberspace Policy Review: Assuring a Trusted and Resilient Information and

    Office of Environmental Management (EM)

    Communications Infrastructure | Department of Energy Cyberspace Policy Review: Assuring a Trusted and Resilient Information and Communications Infrastructure Cyberspace Policy Review: Assuring a Trusted and Resilient Information and Communications Infrastructure The review team of government cybersecurity experts engaged and received input from a broad cross-section of industry, academia, the civil liberties and privacy communities, State governments, international partners, and the

  2. Disability Employment Awareness Month

    Broader source: Energy.gov [DOE]

    Utilizing the talents of all Americans is essential for our Nation to out-innovate, out-educate, and out-build the rest of the world.  During National Disability Employment Awareness Month, we...

  3. Disability Employment Program

    Broader source: Energy.gov [DOE]

    The Department of Energy is committed to fostering a culture of diversity. We recognize that individuals with disabilities are an untapped talent pool and possess the skills and competencies that...

  4. Recruiting People with Disabilities | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Disability Employment » Recruiting People with Disabilities Recruiting People with Disabilities Many of the following websites provide free services for employers: AbilityJobs.com Largest stand-alone resume bank specifically for job seekers with disabilities. Employers can post job opportunities or search resumes to find qualified persons with disabilities. Careers and the Disabled Career Expo for People with Disabilities Brings industry and government together with people with disabilities who

  5. Cryptographic Trust Management Requirements Specification: Version 1.1

    SciTech Connect (OSTI)

    Edgar, Thomas W.

    2009-09-30

    The Cryptographic Trust Management (CTM) Project is being developed for Department of Energy, OE-10 by the Pacific Northwest National Laboratory (PNNL). It is a component project of the NSTB Control Systems Security R&D Program.

  6. Quantum key distribution using card, base station and trusted authority

    DOE Patents [OSTI]

    Nordholt, Jane Elizabeth; Hughes, Richard John; Newell, Raymond Thorson; Peterson, Charles Glen; Rosenberg, Danna; McCabe, Kevin Peter; Tyagi, Kush T; Dallman, Nicholas

    2015-04-07

    Techniques and tools for quantum key distribution ("QKD") between a quantum communication ("QC") card, base station and trusted authority are described herein. In example implementations, a QC card contains a miniaturized QC transmitter and couples with a base station. The base station provides a network connection with the trusted authority and can also provide electric power to the QC card. When coupled to the base station, after authentication by the trusted authority, the QC card acquires keys through QKD with a trusted authority. The keys can be used to set up secure communication, for authentication, for access control, or for other purposes. The QC card can be implemented as part of a smart phone or other mobile computing device, or the QC card can be used as a fillgun for distribution of the keys.

  7. Principles of Faithful Execution in the implementation of trusted objects.

    SciTech Connect (OSTI)

    Tarman, Thomas David; Campbell, Philip LaRoche; Pierson, Lyndon George

    2003-09-01

    We begin with the following definitions: Definition: A trusted volume is the computing machinery (including communication lines) within which data is assumed to be physically protected from an adversary. A trusted volume provides both integrity and privacy. Definition: Program integrity consists of the protection necessary to enable the detection of changes in the bits comprising a program as specified by the developer, for the entire time that the program is outside a trusted volume. For ease of discussion we consider program integrity to be the aggregation of two elements: instruction integrity (detection of changes in the bits within an instruction or block of instructions), and sequence integrity (detection of changes in the locations of instructions within a program). Definition: Faithful Execution (FE) is a type of software protection that begins when the software leaves the control of the developer and ends within the trusted volume of a target processor. That is, FE provides program integrity, even while the program is in execution. (As we will show below, FE schemes are a function of trusted volume size.) FE is a necessary quality for computing. Without it we cannot trust computations. In the early days of computing FE came for free since the software never left a trusted volume. At that time the execution environment was the same as the development environment. In some circles that environment was referred to as a ''closed shop:'' all of the software that was used there was developed there. When an organization bought a large computer from a vendor the organization would run its own operating system on that computer, use only its own editors, only its own compilers, only its own debuggers, and so on. However, with the continuing maturity of computing technology, FE becomes increasingly difficult to achieve

  8. Roadmap to a Sustainable Structured Trusted Employee Program

    SciTech Connect (OSTI)

    Coates, Cameron W; Eisele, Gerhard R

    2013-08-01

    Organizations (facility, regulatory agency, or country) have a compelling interest in ensuring that individuals who occupy sensitive positions affording access to chemical biological, radiological and nuclear (CBRN) materials facilities and programs are functioning at their highest level of reliability. Human reliability and human performance relate not only to security but also focus on safety. Reliability has a logical and direct relationship to trustworthiness for the organization is placing trust in their employees to conduct themselves in a secure, safe, and dependable manner. This document focuses on providing an organization with a roadmap to implementing a successful and sustainable Structured Trusted Employee Program (STEP).

  9. O.A.R. 141-122 - Rules for Granting Easements on Trust and Non...

    Open Energy Info (EERE)

    search OpenEI Reference LibraryAdd to library Legal Document- RegulationRegulation: O.A.R. 141-122 - Rules for Granting Easements on Trust and Non-Trust LandLegal Abstract...

  10. File:03UTDGeothermalSteamLeaseUtahNonTrustLands.pdf | Open Energy...

    Open Energy Info (EERE)

    3UTDGeothermalSteamLeaseUtahNonTrustLands.pdf Jump to: navigation, search File File history File usage Metadata File:03UTDGeothermalSteamLeaseUtahNonTrustLands.pdf Size of this...

  11. File:03UTEGeothermalSteamLeaseUtahTrustLands.pdf | Open Energy...

    Open Energy Info (EERE)

    3UTEGeothermalSteamLeaseUtahTrustLands.pdf Jump to: navigation, search File File history File usage Metadata File:03UTEGeothermalSteamLeaseUtahTrustLands.pdf Size of this preview:...

  12. Improving the trust in results of numerical simulations and scientific data

    Office of Scientific and Technical Information (OSTI)

    analytics (Technical Report) | SciTech Connect Technical Report: Improving the trust in results of numerical simulations and scientific data analytics Citation Details In-Document Search Title: Improving the trust in results of numerical simulations and scientific data analytics This white paper investigates several key aspects of the trust that a user can give to the results of numerical simulations and scientific data analytics. In this document, the notion of trust is related to the

  13. with Disabilities Act Requirements Workplace ADA Requirements...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Americans with Disabilities Act (ADA) is a federal civil rights law that prohibits discrimination in public places against individuals with disabilities. As an employer installing...

  14. Americans with Disabilities Act Signed (1990)

    Broader source: Energy.gov [DOE]

    The Americans with Disabilities Act of 1990 (ADA) prohibits discrimination and ensures equal opportunity for persons with disabilities in employment, State and local government services, public...

  15. Fluid blade disablement tool

    DOE Patents [OSTI]

    Jakaboski, Juan-Carlos (Albuquerque, NM); Hughs, Chance G. (Albuquerque, NM); Todd, Steven N. (Rio Rancho, NM)

    2012-01-10

    A fluid blade disablement (FBD) tool that forms both a focused fluid projectile that resembles a blade, which can provide precision penetration of a barrier wall, and a broad fluid projectile that functions substantially like a hammer, which can produce general disruption of structures behind the barrier wall. Embodiments of the FBD tool comprise a container capable of holding fluid, an explosive assembly which is positioned within the container and which comprises an explosive holder and explosive, and a means for detonating. The container has a concavity on the side adjacent to the exposed surface of the explosive. The position of the concavity relative to the explosive and its construction of materials with thicknesses that facilitate inversion and/or rupture of the concavity wall enable the formation of a sharp and coherent blade of fluid advancing ahead of the detonation gases.

  16. What You Need to Know About the Energy Security Trust

    Broader source: Energy.gov [DOE]

    In his 2013 State of the Union address, President Obama called on Congress to create an Energy Security Trust Fund, which would free American families and business from painful spikes in gas prices. The President’s plan builds on an idea that has bipartisan support from experts including retired admirals and generals and leading CEOs, and it focuses on one goal: shifting America’s cars and trucks off oil entirely.

  17. Lung pair phantom

    DOE Patents [OSTI]

    Olsen, P.C.; Gordon, N.R.; Simmons, K.L.

    1993-11-30

    The present invention is a material and method of making the material that exhibits improved radiation attenuation simulation of real lungs, i.e., an ``authentic lung tissue`` or ALT phantom. Specifically, the ALT phantom is a two-part polyurethane medium density foam mixed with calcium carbonate, potassium carbonate if needed for K-40 background, lanthanum nitrate, acetone, and a nitrate or chloride form of a radionuclide. This formulation is found to closely match chemical composition and linear attenuation of real lungs. The ALT phantom material is made according to established procedures but without adding foaming agents or preparing thixotropic concentrate and with a modification for ensuring uniformity of density of the ALT phantom that is necessary for accurate simulation. The modification is that the polyurethane chemicals are mixed at a low temperature prior to pouring the polyurethane mixture into the mold.

  18. Lung pair phantom

    DOE Patents [OSTI]

    Olsen, Peter C. (West Richland, WA); Gordon, N. Ross (Kennewick, WA); Simmons, Kevin L. (Kennewick, WA)

    1993-01-01

    The present invention is a material and method of making the material that exhibits improved radiation attenuation simulation of real lungs, i.e., an "authentic lung tissue" or ALT phantom. Specifically, the ALT phantom is a two-part polyurethane medium density foam mixed with calcium carbonate, potassium carbonate if needed for K-40 background, lanthanum nitrate, acetone, and a nitrate or chloride form of a radionuclide. This formulation is found to closely match chemical composition and linear attenuation of real lungs. The ALT phantom material is made according to established procedures but without adding foaming agents or preparing thixotropic concentrate and with a modification for ensuring uniformity of density of the ALT phantom that is necessary for accurate simulation. The modification is that the polyurethane chemicals are mixed at a low temperature prior to pouring the polyurethane mixture into the mold.

  19. Early Lung Cancer Detection Program

    Broader source: Energy.gov [DOE]

    Since 2000, DOE has made screening for occupational lung cancer with low-dose helical computed tomography (CT) scans available to workers at high risk for lung cancer. Because former workers undertook essential activities to fulfill the Department's mission, many of them were at risk for lung cancer.

  20. Accommodations for Hearing Disabilities | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Hearing Disabilities Accommodations for Hearing Disabilities hearing-41429_960_720.png The Department offers a variety of accommodations to individuals with hearing disabilities. Available computer and telecommunications access products include: Visual Redundancy on Computers Interpreter Hearing Aid Compatible Phones Speech Amplification Telephone Speech Amplification, Meeting or Conversation. Teletypewriter (TTY) or telecommunications device for the deaf (TDD) TTY with refreshable braille

  1. Secure multi-party communication with quantum key distribution managed by trusted authority

    DOE Patents [OSTI]

    Nordholt, Jane Elizabeth; Hughes, Richard John; Peterson, Charles Glen

    2013-07-09

    Techniques and tools for implementing protocols for secure multi-party communication after quantum key distribution ("QKD") are described herein. In example implementations, a trusted authority facilitates secure communication between multiple user devices. The trusted authority distributes different quantum keys by QKD under trust relationships with different users. The trusted authority determines combination keys using the quantum keys and makes the combination keys available for distribution (e.g., for non-secret distribution over a public channel). The combination keys facilitate secure communication between two user devices even in the absence of QKD between the two user devices. With the protocols, benefits of QKD are extended to multi-party communication scenarios. In addition, the protocols can retain benefit of QKD even when a trusted authority is offline or a large group seeks to establish secure communication within the group.

  2. Secure multi-party communication with quantum key distribution managed by trusted authority

    DOE Patents [OSTI]

    Hughes, Richard John; Nordholt, Jane Elizabeth; Peterson, Charles Glen

    2015-01-06

    Techniques and tools for implementing protocols for secure multi-party communication after quantum key distribution ("QKD") are described herein. In example implementations, a trusted authority facilitates secure communication between multiple user devices. The trusted authority distributes different quantum keys by QKD under trust relationships with different users. The trusted authority determines combination keys using the quantum keys and makes the combination keys available for distribution (e.g., for non-secret distribution over a public channel). The combination keys facilitate secure communication between two user devices even in the absence of QKD between the two user devices. With the protocols, benefits of QKD are extended to multi-party communication scenarios. In addition, the protocols can retain benefit of QKD even when a trusted authority is offline or a large group seeks to establish secure communication within the group.

  3. ANNUAL ACCOMPLISHMENT PLAN UPDATE FOR DISABLED VETERANS

    National Nuclear Security Administration (NNSA)

    variety of minority, disabled, and veterans' organizations. NNSA continues to work on marketing improvements aimed at reaching all segments of the potential workforce. Recruitment...

  4. NMAC 19.2.17 Geophysical Exploration on Unleased State Trust...

    Open Energy Info (EERE)

    2.17 Geophysical Exploration on Unleased State Trust Lands Jump to: navigation, search OpenEI Reference LibraryAdd to library Legal Document- RegulationRegulation: NMAC 19.2.17...

  5. ORNL Trusted Corridors Project: Watts Bar Dam Inland Waterway Project

    SciTech Connect (OSTI)

    Walker, Randy M; Gross, Ian G; Smith, Cyrus M; Hill, David E

    2011-11-01

    Radiation has existed everywhere in the environment since the Earth's formation - in rocks, soil, water, and plants. The mining and processing of naturally occurring radioactive materials for use in medicine, power generation, consumer products, and industry inevitably generate emissions and waste. Radiological measuring devices have been used by industry for years to measure for radiation in undesired locations or simply identify radioactive materials. Since the terrorist attacks on the United States on 9-11-01 these radiation measuring devices have proliferated in many places in our nation's commerce system. DOE, TVA, the Army Corps and ORNL collaborated to test the usefulness of these devices in our nation's waterway system on this project. The purpose of the Watts Bar Dam ORNL Trusted Corridors project was to investigate the security, safety and enforcement needs of local, state and federal government entities for state-of-the-art sensor monitoring in regards to illegal cargo including utilization of the existing infrastructure. TVA's inland waterways lock system is a recognized and accepted infrastructure by the commercial carrier industry. Safety Monitoring activities included tow boat operators, commercial barges and vessels, recreational watercraft and their cargo, identification of unsafe vessels and carriers, and, monitoring of domestic and foreign commercial vessels and cargo identification. Safety Enforcement activities included cargo safety, tracking, identification of hazardous materials, waterway safety regulations, and hazardous materials regulations. Homeland Security and Law Enforcement Applications included Radiological Dispersive Devices (RDD) identification, identification of unsafe or illicit transport of hazardous materials including chemicals and radiological materials, and screening for shipments of illicit drugs. In the Fall of 2005 the SensorNet funding for the project expired. After several unsuccessful attempts to find a Federal sponsor to continue with the project, the Watts Bar Dam Project was canceled and the Exploranium radiation monitors were removed from the doors of Watts Bar Dam in early 2006. The DHS Domestic Nuclear Detection Office decided to proceed with a Pilot building on the ORNL work performed at the TN and SC weigh stations in the highway sector of the Trusted Corridors project and eventually expanded it to other southern states under the name of Southeastern Corridor Pilot Project (SETCP). Many of the Phase I goals were achieved however real-world test data of private watercraft and barges was never obtained.

  6. Santa Fe New Mexican: For cybersecurity, in quantum encryption we trust

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    For cybersecurity, in quantum encryption we trust Santa Fe New Mexican: For cybersecurity, in quantum encryption we trust Los Alamos physicists developed a quantum random number generator and a quantum communication system, which exploit the laws of quantum physics to improve cybersecurity. September 13, 2015 Los Alamos physicists developed a quantum random number generator and a quantum communication system, both of which exploit the weird and immutable laws of quantum physics to improve

  7. Improving the trust in results of numerical simulations and scientific data

    Office of Scientific and Technical Information (OSTI)

    analytics (Technical Report) | SciTech Connect Technical Report: Improving the trust in results of numerical simulations and scientific data analytics Citation Details In-Document Search Title: Improving the trust in results of numerical simulations and scientific data analytics × You are accessing a document from the Department of Energy's (DOE) SciTech Connect. This site is a product of DOE's Office of Scientific and Technical Information (OSTI) and is provided as a public service. Visit

  8. Accommodations for Physical Disabilities | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Physical Disabilities Accommodations for Physical Disabilities ADA-107-2T.jpg The Department offers a variety of accommodations to individuals with mobility limitations. Available computer and telecommunications access products include: Sequential Keystroke Input Key Repeat Rate Control Keyboard Macros Alternative Keyboards Non-Keyboard Dependent Input Devices Word Prediction Packages Speech Recognition Robotic Devices Mouse Alternatives Keyguard Optical Character Recognition Speaker Phone

  9. Self-Identification of Disability | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Self-Identification of Disability Self-Identification of Disability PDF icon Self-Identification of Disability More Documents & Publications DOE Emergency Special Needs Self-Identification Form Operational Plan and Desktop Reference for the Disability Employment Program Enforcement Letter, EG&G Mound Applied Technologies - August 22, 1996

  10. Jefferson Lab Leadership Council - Dr. Allison Lung

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Associate Director, Dr. Allison Lung Allison Lung Associate Director, 12 GeV Upgrade Project Allison Lung was appointed the assistant director for the Thomas Jefferson National Accelerator Facility in October 2002. As assistant director, Lung is responsible for formulating and leading the JLab Continual Improvement Program, and responding to requests from JLab stakeholders. She organizes support and documentation for funding campaigns and collaborates closely with the lab director in matters

  11. Notices Disabled, 1401 S. Clark Street, Suite

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    913 Federal Register / Vol. 78, No. 240 / Friday, December 13, 2013 / Notices Disabled, 1401 S. Clark Street, Suite 10800, Arlington, Virginia 22202-4149. FOR FURTHER INFORMATION CONTACT: Barry S. Lineback, Telephone: (703) 603-7740, Fax: (703) 603-0655, or email CMTEFedReg@AbilityOne.gov. SUPPLEMENTARY INFORMATION: Addition On 6/28/2013 (78 FR 38952-38953), the Committee for Purchase From People Who Are Blind or Severely Disabled published notice of proposed addition to the Procurement List.

  12. Defined Benefit Eligible Disability Benefit Program Summary

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    LANS Defined Benefit Eligible Disability Program Benefit Program Summary Effective June 1, 2006 IMPORTANT This is a summary of the highlights of the LANS Defined Benefit Eligible Disability Program, a component of the LANS Welfare Benefit Plan for Employees, ERISA Plan 501 ("Plan"). Receipt of this document and/or your participation in the Plan and any benefit programs under the Plan do not guarantee your employment or any rights or benefits under the Plan. LANS reserves the right to

  13. ANNUAL ACCOMPLISHMENT PLAN UPDATE FOR DISABLED VETERANS

    National Nuclear Security Administration (NNSA)

    ffirmative Action Program A FY 2009 Annual Report October 2009 U.S. Department of Energy National Nuclear Security Administration FY 2009 NNSA DVAAP Report - October 16, 2009 2 This page intentionally left blank FY 2009 NNSA DVAAP Report - October 16, 2009 4 Annual Accomplishment Report for Disabled Veterans Affirmative Action Program (DVAAP) FY 2009 INTRODUCTION This report represents the FY 2009 accomplishments for disabled Veterans for the U.S. Department of Energy's National Nuclear Security

  14. Notices Disabled, 1401 S. Clark Street, Suite

    Energy Savers [EERE]

    13 Federal Register / Vol. 78, No. 240 / Friday, December 13, 2013 / Notices Disabled, 1401 S. Clark Street, Suite 10800, Arlington, Virginia 22202-4149. FOR FURTHER INFORMATION CONTACT: Barry S. Lineback, Telephone: (703) 603-7740, Fax: (703) 603-0655, or email CMTEFedReg@AbilityOne.gov. SUPPLEMENTARY INFORMATION: Addition On 6/28/2013 (78 FR 38952-38953), the Committee for Purchase From People Who Are Blind or Severely Disabled published notice of proposed addition to the Procurement List.

  15. Accommodations for Vision Disabilities | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Vision Disabilities Accommodations for Vision Disabilities glasses.png The Department offers a variety of accommodations to individuals with vision impairment. Available computer and telecommunications access products include: "Low Vision" Accommodations Glare Protection Screen Large Monitor with High Resolution (19" - 25") Magnified Display of Computer Screen Magnified Display of Hardcopy Material Large Print Production Copy Machine with Enlarging and Reducing Capability

  16. CIGNA Study Uncovers Relationship of Disabilities to Total Benefits Costs

    Broader source: Energy.gov [DOE]

    The findings of a new study reveal an interesting trend. Integrating disability programs with health care programs can potentially lower employers' total benefits costs and help disabled employees get back to work sooner and stay at work.

  17. BNL Technical Services Awarded Service-Disabled Veteran-Owned...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    BNL Technical Services Awarded Service-Disabled Veteran-Owned Small Business of the Year BNL Technical Services Awarded Service-Disabled Veteran-Owned Small Business of the Year ...

  18. Celebrating the Anniversary of the Americans with Disabilities Act

    Broader source: Energy.gov [DOE]

    This day in history - in 1990 to be exact - the Americans with Disabilities Act (ADA) was signed into law. This civil rights legislation helps ensure that all citizens, regardless of disability,...

  19. Disability Employment POCs | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Disability Employment POCs Disability Employment POCs NAME ORGANIZATION PH # EMAL Donna Friend Headquarters Policy 202-586-5880 donna.friend@hq.doe.gov Rhonda Kennedy Headquarters Operations 202-586-3544 rhonda.kennedy@hq.doe.gov Tamara Lockhart-Rowley Bonneville Power Administration 530-230-5329 tlockhartrowley@bpa.gov Donna Wachter EE/Golden Field Office 720-356-1807 donna.wachter@go.doe.gov Michelle Litmer EMCBC 513-246-0514 michelle.litmer@emcbc.doe.gov Lisa Bonser EM/ Richland Operations

  20. Operational Plan and Desktop Reference for the Disability Employment

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Program | Department of Energy Operational Plan and Desktop Reference for the Disability Employment Program Operational Plan and Desktop Reference for the Disability Employment Program The Department of Energy's Plan and Desktop Reference for hiring individuals with disabilities. PDF icon Final-SOP-Disability-Employment-FY14.pdf Responsible Contacts Donna Friend HUMAN RESOURCES SPECIALIST E-mail donna.friend@hq.doe.dov Phone 202-586-5880 More Documents & Publications Operational Plan and

  1. Disabled Veterans Affirmative Action Plan | Department of Energy

    Office of Environmental Management (EM)

    Disabled Veterans Affirmative Action Plan Disabled Veterans Affirmative Action Plan Guide for the Disabled Veterans' Affirmative Action Program (DVAAP) PDF icon FY16 DVAAP Plan.pdf Responsible Contacts Donna Friend HUMAN RESOURCES SPECIALIST E-mail donna.friend@hq.doe.dov Phone 202-586-5880 More Documents & Publications Roles & Responsibilities Operational Plan and Desktop Reference for the Veterans Employment Program Operational Plan and Desktop Reference for the Disability Employment

  2. Joshua DeLung | Department of Energy

    Office of Environmental Management (EM)

    Joshua DeLung About Us Joshua DeLung Joshua DeLung is an Account Manager at ENC Marketing & Communications and the Executive Editor at Relatively Journalizing. Most Recent EnerG2 Develops New Approach to EV Energy Storage November 16 A Spin on Technology: Extracting Value from Wasted Heat November 12 Solar-Powered, School-Zone Safety November 8

  3. Golden Field Office Disability Awareness Month Event

    Broader source: Energy.gov [DOE]

    Come join us for a Disability Awareness Month program on Monday, October 29, 2012 in Bldg. 17, 4th floor, from 10:00-11:00 am.   We will have a couple  of performers from a Theatre group named...

  4. ANNUAL ACCOMPLISHMENT PLAN UPDATE FOR DISABLED VETERANS

    National Nuclear Security Administration (NNSA)

    FY 2012 NNSA DVAAP Report 1 Disabled Veterans Affirmative Action Program FY 2012 Accomplishment Report Table of Contents October 2012 U.S. Department of Energy National Nuclear Security Administration FY 2012 NNSA DVAAP Report 2 Table of Contents * Plan Certification .........................................................................................Page 3 * Agency DVAAP Executive Summary................................................................. Page 4 * Organizational

  5. Workplace Charging Challenge Partner: American Lung Association in Colorado

    Broader source: Energy.gov [DOE]

    The mission of the American Lung Association in Colorado (ALAC) is to improve lung health and prevent lung disease. Encouraging the use of plug-in electric vehicles is essential to improving local...

  6. Technical Qualifications for Treating Photovoltaic Assets as Real Property by Real Estate Investment Trusts (REITs)

    SciTech Connect (OSTI)

    Feldman, D.; Mendelsohn, M.; Coughlin, J.

    2012-06-01

    It has been proposed that Real Estate Investment Trusts (REITs) have the potential to lower the cost and increase the adoption of photovoltaic systems (PV) by offering a more attractive source of capital. The purpose of this paper is to explain the fundamental physical characteristics of PV and compare them to the characteristics of 'real' property, to help determine whether REITs can own PV systems.

  7. Response of Human Lung Epithelial Cells to Engineered Nanoparticles...

    Office of Scientific and Technical Information (OSTI)

    Response of Human Lung Epithelial Cells to Engineered Nanoparticles. Citation Details In-Document Search Title: Response of Human Lung Epithelial Cells to Engineered Nanoparticles. ...

  8. Structures of Lung Cancer-Derived EGFR Mutants and Inhibitor...

    Office of Scientific and Technical Information (OSTI)

    Structures of Lung Cancer-Derived EGFR Mutants and Inhibitor Complexes: Mechanism of ... Citation Details In-Document Search Title: Structures of Lung Cancer-Derived EGFR Mutants ...

  9. Microsoft Word - Los Alamos National Security, LLC_SUPP DISABILITY...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    injury. This highlight sheet is an overview of your Supplemental Disability Insurance. Once a group policy is issued to your employer, a certificate of Insurance will be available...

  10. Weekly Address: Time to Create the Energy Security Trust | Department of

    Broader source: Energy.gov (indexed) [DOE]

    Energy Matt Compton Deputy Director of Online Content for the Office of Digital Strategy at the White House. Editor's Note: This blog is cross-posted from WhiteHouse.gov. President Obama discusses the need to harness American energy in order to reduce our dependence on oil and make the United States a magnet for new jobs. He highlights his all-of-the-above approach to American energy -- including a proposal to establish an Energy Security Trust, which invests in research that will help shift

  11. Linear dimensions and volumes of human lungs

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Hickman, David P.

    2012-03-30

    TOTAL LUNG Capacity is defined as “the inspiratory capacity plus the functional residual capacity; the volume of air contained in the lungs at the end of a maximal inspiration; also equals vital capacity plus residual volume” (from MediLexicon.com). Within the Results and Discussion section of their April 2012 Health Physics paper, Kramer et al. briefly noted that the lungs of their experimental subjects were “not fully inflated.” By definition and failure to obtain maximal inspiration, Kramer et. al. did not measure Total Lung Capacity (TLC). The TLC equation generated from this work will tend to underestimate TLC and does notmore » improve or update total lung capacity data provided by ICRP and others. Likewise, the five linear measurements performed by Kramer et. al. are only representative of the conditions of the measurement (i.e., not at-rest volume, but not fully inflated either). While there was significant work performed and the data are interesting, the data does not represent a maximal situation, a minimal situation, or an at-rest situation. Moreover, while interesting, the linear data generated by this study is limited by the conditions of the experiment and may not be fully comparative with other lung or inspiratory parameters, measures, or physical dimensions.« less

  12. Radiation-induced lung injury

    SciTech Connect (OSTI)

    Rosiello, R.A.; Merrill, W.W. )

    1990-03-01

    The use of radiation therapy is limited by the occurrence of the potentially fatal clinical syndromes of radiation pneumonitis and fibrosis. Radiation pneumonitis usually becomes clinically apparent from 2 to 6 months after completion of radiation therapy. It is characterized by fever, cough, dyspnea, and alveolar infiltrates on chest roentgenogram and may be difficult to differentiate from infection or recurrent malignancy. The pathogenesis is uncertain, but appears to involve both direct lung tissue toxicity and an inflammatory response. The syndrome may resolve spontaneously or may progress to respiratory failure. Corticosteroids may be effective therapy if started early in the course of the disease. The time course for the development of radiation fibrosis is later than that for radiation pneumonitis. It is usually present by 1 year following irradiation, but may not become clinically apparent until 2 years after radiation therapy. It is characterized by the insidious onset of dyspnea on exertion. It most often is mild, but can progress to chronic respiratory failure. There is no known successful treatment for this condition. 51 references.

  13. TRUST: A Computer Program for Variably Saturated Flow in Multidimensional, Deformable Media

    SciTech Connect (OSTI)

    Reisenauer, A. E.; Key, K. T.; Narasimhan, T. N.; Nelson, R. W.

    1982-01-01

    The computer code, TRUST. provides a versatile tool to solve a wide spectrum of fluid flow problems arising in variably saturated deformable porous media. The governing equations express the conservation of fluid mass in an elemental volume that has a constant volume of solid. Deformation of the skeleton may be nonelastic. Permeability and compressibility coefficients may be nonlinearly related to effective stress. Relationships between permeability and saturation with pore water pressure in the unsaturated zone may include hysteresis. The code developed by T. N. Narasimhan grew out of the original TRUNP code written by A. L. Edwards. The code uses an integrated finite difference algorithm for numerically solving the governing equation. Narching in time is performed by a mixed explicit-implicit numerical procedure in which the time step is internally controlled. The time step control and related feature in the TRUST code provide an effective control of the potential numerical instabilities that can arise in the course of solving this difficult class of nonlinear boundary value problem. This document brings together the equations, theory, and users manual for the code as well as a sample case with input and output.

  14. Faith Enterprises Inc. A Service Disabled Veteran-Owned Small...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Faith Enterprises Inc. A Service Disabled Veteran-Owned Small Business Security When the Air Force asked Sandia to deliver complex security upgrades to a facility on Kirtland Air...

  15. Rebate Program Serves Alaskans with Disabilities | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Rebate Program Serves Alaskans with Disabilities Rebate Program Serves Alaskans with Disabilities July 21, 2010 - 2:10pm Addthis Lorelei Laird Writer, Energy Empowers What are the key facts? Energy efficient appliances are made more affordable in rural Alaska thanks to $500 rebates. With rates of up to .50 kWh in Alaska, energy efficient appliances reduce energy bills. Alaska applies Recovery Act funding to lower administrative costs of their rebate program. According to the U.S. Census

  16. Celebrating the Anniversary of the Americans with Disabilities Act

    Broader source: Energy.gov [DOE]

    We are actively working to make the Energy Department a model employer for individuals with disabilities, that we're responding to the needs of our employees with disabilities, and that we're addressing Equal Employment Opportunity discrimination complaints quickly and effectively under the law. We're also working to make Energy.gov 508 compliant to deliver resources and services to you in more accessible ways.

  17. Master Limited Partnerships and Real Estate Investment Trusts: Opportunities and Potential Complications for Renewable Energy

    SciTech Connect (OSTI)

    Feldman, D.; Settle, E.

    2013-11-01

    Master Limited Partnerships (MLPs) and Real Estate Investment Trusts (REITs) are two proposed investment vehicles which have the potential to lower renewable energy assets' high cost of capital; a critical factor in the Department of Energy's goal for renewable energy to achieve grid-parity with traditional sources of electric generation. Due to current U.S. federal income tax laws, regulations, and administrative interpretations, REITs and MLPs cannot finance a significant portion of the cost of renewable energy assets. Efforts are underway to alter these rules by changing the definition of 'real property' (REIT) and 'qualified income' (MLP). However, even with rule changes, both investment vehicles have structural challenges to efficiently finance renewable energy assets. Among them are 1) effectively utilizing the U.S. federal income tax incentives; 2) administratively structuring the investments to not be overly onerous or complicated, given the potential for pooling a relatively large amount of small assets; and 3) attracting and retaining a large enough investment community to participate in the funding opportunities. This report summarizes these challenges so that if proposed federal changes are made, stakeholders have an understanding of the possible outcomes.

  18. Method and apparatus for measuring lung density by Compton backscattering

    DOE Patents [OSTI]

    Loo, B.W.; Goulding, F.S.

    1988-03-11

    The density of the lung of a patient suffering from pulmonary edema is monitored by irradiating the lung by a single collimated beam of monochromatic photons and measuring the energies of photons compton back-scattered from the lung by a single high-resolution, high-purity germanium detector. A compact system geometry and a unique data extraction scheme are utilized to minimize systematic errors due to the presence of the chestwall and multiple scattering. 11 figs., 1 tab.

  19. Method and apparatus for measuring lung density by Compton backscattering

    DOE Patents [OSTI]

    Loo, Billy W. (Oakland, CA); Goulding, Frederick S. (Lafayette, CA)

    1991-01-01

    The density of the lung of a patient suffering from pulmonary edema is monitored by irradiating the lung by a single collimated beam of monochromatic photons and measuring the energies of photons Compton backscattered from the lung by a single high-resolution, high-purity germanium detector. A compact system geometry and a unique data extraction scheme are utilized to monimize systematic errors due to the presence of the chestwall and multiple scattering.

  20. Sex-specific differences in hyperoxic lung injury in mice: Implications for acute and chronic lung disease in humans

    SciTech Connect (OSTI)

    Lingappan, Krithika, E-mail: lingappa@bcm.edu [Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States); Jiang, Weiwu; Wang, Lihua; Couroucli, Xanthi I. [Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States); Barrios, Roberto [Department of Pathology and Genomic Medicine, The Methodist Hospital Physician Organization, 6565 Fannin Street, Suite M227, Houston, TX 77030 (United States); Moorthy, Bhagavatula [Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States)

    2013-10-15

    Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO{sub 2} > 0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F{sub 2} alpha (8-iso-PGF 2?) (LCMS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. Cytochrome P450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2? levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F > M) and VEGF (M > F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans. - Highlights: Male mice were more susceptible to hyperoxic lung injury than females. Sex differences in inflammatory markers were observed. CYP1A expression was higher in females after hyperoxia exposure.

  1. OPM Model Strategies for Recuitment and Hiring of People With Disabilities

    Broader source: Energy.gov [DOE]

    OPM Guidance on creating and implementing a strategic approach to hiring individuals with disabilities for each Federal Agency.

  2. Dose impact in radiographic lung injury following lung SBRT: Statistical analysis and geometric interpretation

    SciTech Connect (OSTI)

    Yu, Victoria; Kishan, Amar U.; Cao, Minsong; Low, Daniel; Lee, Percy; Ruan, Dan

    2014-03-15

    Purpose: To demonstrate a new method of evaluating dose response of treatment-induced lung radiographic injury post-SBRT (stereotactic body radiotherapy) treatment and the discovery of bimodal dose behavior within clinically identified injury volumes. Methods: Follow-up CT scans at 3, 6, and 12 months were acquired from 24 patients treated with SBRT for stage-1 primary lung cancers or oligometastic lesions. Injury regions in these scans were propagated to the planning CT coordinates by performing deformable registration of the follow-ups to the planning CTs. A bimodal behavior was repeatedly observed from the probability distribution for dose values within the deformed injury regions. Based on a mixture-Gaussian assumption, an Expectation-Maximization (EM) algorithm was used to obtain characteristic parameters for such distribution. Geometric analysis was performed to interpret such parameters and infer the critical dose level that is potentially inductive of post-SBRT lung injury. Results: The Gaussian mixture obtained from the EM algorithm closely approximates the empirical dose histogram within the injury volume with good consistency. The average Kullback-Leibler divergence values between the empirical differential dose volume histogram and the EM-obtained Gaussian mixture distribution were calculated to be 0.069, 0.063, and 0.092 for the 3, 6, and 12 month follow-up groups, respectively. The lower Gaussian component was located at approximately 70% prescription dose (35 Gy) for all three follow-up time points. The higher Gaussian component, contributed by the dose received by planning target volume, was located at around 107% of the prescription dose. Geometrical analysis suggests the mean of the lower Gaussian component, located at 35 Gy, as a possible indicator for a critical dose that induces lung injury after SBRT. Conclusions: An innovative and improved method for analyzing the correspondence between lung radiographic injury and SBRT treatment dose has been demonstrated. Bimodal behavior was observed in the dose distribution of lung injury after SBRT. Novel statistical and geometrical analysis has shown that the systematically quantified low-dose peak at approximately 35 Gy, or 70% prescription dose, is a good indication of a critical dose for injury. The determined critical dose of 35 Gy resembles the critical dose volume limit of 30 Gy for ipsilateral bronchus in RTOG 0618 and results from previous studies. The authors seek to further extend this improved analysis method to a larger cohort to better understand the interpatient variation in radiographic lung injury dose response post-SBRT.

  3. Job Seekers with Disabilities | National Nuclear Security Administration

    National Nuclear Security Administration (NNSA)

    Seekers with Disabilities | National Nuclear Security Administration Facebook Twitter Youtube Flickr RSS People Mission Managing the Stockpile Preventing Proliferation Powering the Nuclear Navy Emergency Response Recapitalizing Our Infrastructure Countering Nuclear Terrorism About Our Programs Our History Who We Are Our Leadership Our Locations Budget Our Operations Library Bios Congressional Testimony Fact Sheets Newsletters Press Releases Photo Gallery Jobs Apply for Our Jobs Our Jobs Working

  4. Diesel Exhaust Dispersion in a Phospholipid Lung Surfactant | Department of

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Energy Exhaust Dispersion in a Phospholipid Lung Surfactant Diesel Exhaust Dispersion in a Phospholipid Lung Surfactant 2005 Diesel Engine Emissions Reduction (DEER) Conference Presentations and Posters PDF icon 2005_deer_wallace.pdf More Documents & Publications IN VITRO MUTAGENIC AND DNA AND CHROMOSOMAL DAMAGE ACTIVITY BY SURFACTANT DISPERSION OR SOLVENT EXTRACT OF A REFERENCE DIESEL EXHAUST PARTICULATE MATERIAL In Vitro Genotoxicity of Gasoline and Diesel Engine Vehicle Exhaust

  5. Response of Human Lung Epithelial Cells to Engineered Nanoparticles.

    Office of Scientific and Technical Information (OSTI)

    (Conference) | SciTech Connect Response of Human Lung Epithelial Cells to Engineered Nanoparticles. Citation Details In-Document Search Title: Response of Human Lung Epithelial Cells to Engineered Nanoparticles. Abstract not provided. Authors: Bachand, George ; Bachand, Marlene ; Brozik, Susan Marie ; Achyuthan, Komandoor ; Allen, Amy Publication Date: 2011-10-01 OSTI Identifier: 1120230 Report Number(s): SAND2011-7265C 482189 DOE Contract Number: DE-AC04-94AL85000 Resource Type: Conference

  6. Y-12 employee engineers success for disabled adults | Y-12 National...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    case management, training, housing, jobs and other services for adults with severe disabilities. The future 25,000 square foot building will house a medical and nursing center,...

  7. Voluntary Self-Identification of Disability Form CC-305 OMB Control Number 1250-0005

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Voluntary Self-Identification of Disability Form CC-305 OMB Control Number 1250-0005 Expires 1/31/2017 Page 1 of 2 Why are you being asked to complete this form? Because we do business with the government, we must reach out to, hire, and provide equal opportunity to qualified people with disabilities. i To help us measure how well we are doing, we are asking you to tell us if you have a disability or if you ever had a disability. Completing this form is voluntary, but we hope that you will

  8. KPaul A Service Disabled Veteran-Owned Small Business

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    KPaul A Service Disabled Veteran-Owned Small Business Jennifer Muth's initial phone call put her in touch with Ann Riley, Sandia's Business Point of Contact. "I work with all new company inquiries to make sure they have the qualifications to become a Sandia supplier," comments Ann. "I saw right away that the company had the potential to be a successful supplier for Sandia. Jennifer understood our market and what we buy and came prepared with all of the information necessary to get

  9. SU-E-J-185: Gated CBCT Imaging for Positioning Moving Lung Tumor in Lung SBRT Treatment

    SciTech Connect (OSTI)

    Li, X; Li, T; Zhang, Y; Burton, S; Karlovits, B; Clump, D; Heron, D; Huq, M

    2014-06-01

    Purpose: Lung stereo-tactic body radiotherapy(SBRT) treatment requires high accuracy of lung tumor positioning during treatment, which is usually accomplished by free breathing Cone-Beam computerized tomography (CBCT) scan. However, respiratory motion induced image artifacts in free breathing CBCT may degrade such positioning accuracy. The purpose of this study is to investigate the feasibility of gated CBCT imaging for lung SBRT treatment. Methods: Six Lung SBRT patients were selected for this study. The respiratory motion of the tumors ranged from 1.2cm to 3.5cm, and the gating windows for all patients were set between 35% and 65% of the respiratory phases. Each Lung SBRT patient underwent free-breathing CBCT scan using half-fan scan technique. The acquired projection images were transferred out for off-line analyses. An In-house semi-automatic algorithm was developed to trace the diaphragm movement from those projection images to acquire a patient's specific respiratory motion curve, which was used to correlate respiratory phases with each projection image. Afterwards, a filtered back-projection algorithm was utilized to reconstruct the gated CBCT images based on the projection images only within the gating window. Results: Target volumes determined by free breathing CBCT images were 71.9%72% bigger than the volume shown in gated CBCT image. On the contrary, the target volume differences between gated CBCT and planning CT images at exhale stage were 5.8%2.4%. The center to center distance of the targets shown in free breathing CBCT and gated CBCT images were 9.28.1mm. For one particular case, the superior boundary of the target was shifted 15mm between free breathing CBCT and gated CBCT. Conclusion: Gated CBCT imaging provides better representation of the moving lung tumor with less motion artifacts, and has the potential to improve the positioning accuracy in lung SBRT treatment.

  10. Residential radon and lung cancer incidence in a Danish cohort

    SciTech Connect (OSTI)

    Braeuner, Elvira V.; Andersen, Claus E.; Sorensen, Mette; Jovanovic Andersen, Zorana; Center for Epidemiology Screening, Department of Public Health, University of Copenhagen ; Gravesen, Peter; Ulbak, Kaare; Hertel, Ole; Pedersen, Camilla; Overvad, Kim; Tjonneland, Anne; Raaschou-Nielsen, Ole

    2012-10-15

    High-level occupational radon exposure is an established risk factor for lung cancer. We assessed the long-term association between residential radon and lung cancer risk using a prospective Danish cohort using 57,053 persons recruited during 1993-1997. We followed each cohort member for cancer occurrence until 27 June 2006, identifying 589 lung cancer cases. We traced residential addresses from 1 January 1971 until 27 June 2006 and calculated radon at each of these addresses using information from central databases regarding geology and house construction. Cox proportional hazards models were used to estimate incidence rate ratios (IRR) and 95% confidence intervals (CI) for lung cancer risk associated with residential radon exposure with and without adjustment for sex, smoking variables, education, socio-economic status, occupation, body mass index, air pollution and consumption of fruit and alcohol. Potential effect modification by sex, traffic-related air pollution and environmental tobacco smoke was assessed. Median estimated radon was 35.8 Bq/m{sup 3}. The adjusted IRR for lung cancer was 1.04 (95% CI: 0.69-1.56) in association with a 100 Bq/m{sup 3} higher radon concentration and 1.67 (95% CI: 0.69-4.04) among non-smokers. We found no evidence of effect modification. We find a positive association between radon and lung cancer risk consistent with previous studies but the role of chance cannot be excluded as these associations were not statistically significant. Our results provide valuable information at the low-level radon dose range.

  11. Perfusion lung scan: an aid in detection of lymphangitic carcinomatosis

    SciTech Connect (OSTI)

    Bates, S.E.; Tranum, B.L.

    1982-07-15

    Lymphangitic carcinomatosis is usually a late manifestation of metastatic disease. The patient usually presents with cough or dyspnea, and the chest radiograph is often nondiagnostic. Two patients are presented who developed symptoms while on adjuvant chemotherapy. Both had abnormal perfusion lung scans. One had matching ventilation defects; the other a normal ventilation study. Biopsy revealed metastatic carcinoma; in one case tumor was seen in both the pulmonary lymphatics and arterioles; in the other, tumor was identified but the site could not be specified. The radionuclide lung scan is a technique which can speed diagnosis and institution of therapy in lymphangitic carcinomatosis.

  12. SU-E-T-351: Verification of Monitor Unit Calculation for Lung...

    Office of Scientific and Technical Information (OSTI)

    States Language: English Subject: 60 APPLIED LIFE SCIENCES; COMPUTERIZED TOMOGRAPHY; LUNGS; MONTE CARLO METHOD; RADIATION DOSES; RADIATION MONITORS; RADIOTHERAPY; SPATIAL...

  13. Modifications of lung clearance mechanisms by acute influenza A infection

    SciTech Connect (OSTI)

    Levandowski, R.A.; Gerrity, T.R.; Garrard, C.S.

    1985-10-01

    Four volunteers with naturally acquired, culture-proved influenza A infection inhaled a radiolabeled aerosol to permit investigation of lung mucociliary clearance mechanisms during and after symptomatic illness. Mucus transport in the trachea was undetectable when monitored with an external multidetector probe within 48 hours of the onset of the illness, but was found at a normal velocity by 1 week in three of the four subjects. In two volunteers who coughed 23 to 48 times during the 4.5-hour observation period, whole lung clearance was as fast within the first 48 hours of illness as during health 3 months later in spite of the absence of measurable tracheal mucus transport. Conversely, in spite of the return 1 week later of mucus transport at velocities expected in the trachea, whole lung clearance for the 4.5-hour period was slowed in two volunteers who coughed less than once an hour. The data offer evidence that cough is important in maintaining lung clearance for at least several days after symptomatic influenza A infection when other mechanisms that depend on ciliary function are severely deficient.

  14. BNL Technical Services Awarded Service-Disabled Veteran-Owned Small

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Business of the Year | Department of Energy BNL Technical Services Awarded Service-Disabled Veteran-Owned Small Business of the Year BNL Technical Services Awarded Service-Disabled Veteran-Owned Small Business of the Year October 1, 2014 - 10:39am Addthis DOE Chief of Staff Kevin Knobloch (l) and DOE OSDBU Director John Hale III (r) present Service-Disabled Veteran-Owned Small Business of the Year to BNL Tech President and Chief Financial Officer Wilson Stevenson and BNL Tech Chief Executive

  15. Elevated epidermal growth factor receptor binding in plutonium-induced lung tumors from dogs

    SciTech Connect (OSTI)

    Leung, F.C.; Bohn, L.R.; Dagle, G.E. )

    1991-04-01

    The objective of this study is to examine and characterize epidermal growth factor receptor (EGF-R) binding in inhaled plutonium-induced canine lung-tumor tissue and to compare it with that in normal canine lung tissue. Crude membrane preparations from normal and lung-tumor tissue from beagle dogs were examined in a radioreceptor assay, using {sup 125}I-labeled epidermal growth factor (EGF) as a ligand. Specific EGF receptor binding was determined in the presence of excess unlabeled EGF. We have examined EGF receptor binding in eight lung-tumor samples obtained from six dogs. Epidermal growth factor receptor binding was significantly greater in lung-tumor samples (31.38%) compared with that in normal lung tissue (3.76%). Scatchard plot analysis from the displacement assay revealed that there was no statistical difference in the binding affinity but significantly higher concentration of EGF-R sites in the lung-tumor tissue (619 fmol/mg) than in normal lung tissue (53 fmol/mg). The increase in EGF-R number in plutonium-induced dog lung tumors does not seem to correlate with increase in the initial lung burden exposure to plutonium. Our results demonstrate that there is a significant increase in EGF-R binding in inhaled plutonium-induced dog lung tumors.

  16. Lung Radiofrequency Ablation for the Treatment of Unresectable Recurrent Non-Small-Cell Lung Cancer After Surgical Intervention

    SciTech Connect (OSTI)

    Kodama, Hiroshi, E-mail: h-kodama@clin.medic.mie-u.ac.jp; Yamakado, Koichiro; Takaki, Haruyuki; Kashima, Masataka; Uraki, Junji; Nakatsuka, Atsuhiro [Mie University School of Medicine, Department of Radiology (Japan); Takao, Motoshi [Mie University School of Medicine, Department of Thoracic Surgery (Japan); Taguchi, Osamu [Mie University School of Medicine, Department of Internal Medicine (Japan); Yamada, Tomomi [Mie University School of Medicine, Department of Translational Medicine (Japan); Takeda, Kan [Mie University School of Medicine, Department of Radiology (Japan)

    2012-06-15

    Purpose: A retrospective evaluation was done of clinical utility of lung radiofrequency (RF) ablation in recurrent non-small-cell lung cancer (NSCLC) after surgical intervention. Methods: During May 2003 to October 2010, 44 consecutive patients (26 male and 18 female) received curative lung RF ablation for 51 recurrent NSCLC (mean diameter 1.7 {+-} 0.9 cm, range 0.6 to 4.0) after surgical intervention. Safety, tumor progression rate, overall survival, and recurrence-free survival were evaluated. Prognostic factors were evaluated in multivariate analysis. Results: A total of 55 lung RF sessions were performed. Pneumothorax requiring pluerosclerosis (n = 2) and surgical suture (n = 1) were the only grade 3 or 4 adverse events (5.5%, 3 of 55). During mean follow-up of 28.6 {+-} 20.3 months (range 1 to 98), local tumor progression was found in 5 patients (11.4%, 5 of 44). The 1-, 3-, and 5-year overall survival rates were 97.7, 72.9, and 55.7%, respectively. The 1- and 3-year recurrence-free survival rates were 76.7 and 41.1%, respectively. Tumor size and sex were independent significant prognostic factors in multivariate analysis. The 5-year survival rates were 73.3% in 18 women and 60.5% in 38 patients who had small tumors measuring {<=}3 cm. Conclusion: Our results suggest that lung RF ablation is a safe and useful therapeutic option for obtaining long-term survival in treated patients.

  17. National Nuclear Security Administration Contractors' Disability Compensation and Return-to-Work Programs, IG-0867

    Office of Environmental Management (EM)

    Audit Report The National Nuclear Security Administration Contractors' Disability Compensation and Return-to-Work Programs DOE/IG-0867 June 2012 U.S. Department of Energy Office of Inspector General Office of Audits and Inspections Department of Energy Washington, DC 20585 June 18, 2012 MEMORANDUM FOR THE SECRETARY FROM: Gregory H. Friedman Inspector General SUBJECT: INFORMATION: Audit Report on "NNSA Contractors' Disability Compensation and Return-to-Work Programs" INTRODUCTION AND

  18. Perfusion lung scan: an aid in detection of lymphangitic carcinomatosis

    SciTech Connect (OSTI)

    Bates, S.E.; Tranum, B.L.

    1982-07-15

    Lymphangitic carcinomatosis is usually a late manifestation of metastatic disease. The patient usually presents with cough or dyspnea, and the chest radiograph is often nondiagnostic. Two patients are presented who developed symptoms while on adjuvant chemotherapy. Both had abnormal perfusion lung scans. One had matching ventilation defects; the other a normal ventilation study. Biopsy revealed metastatic carcinoma; in one case tumor was seen in both the pulmonary lymphatics and arterioles; in technique which can speed diagnosis and institution of therapy in lymphangitic carcinomatosis.

  19. Frizzled-8 as a putative therapeutic target in human lung cancer

    SciTech Connect (OSTI)

    Wang, Hua-qing; Department of Medical Oncology, Tianjin Medical University Cancer Hospital, Tianjin 300060 ; Xu, Mei-lin; Ma, Jie; Zhang, Yi; Xie, Cong-hua

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Fzd-8 is over-expressed in human lung cancer. Black-Right-Pointing-Pointer shRNA knock-down of Fzd-8 inhibits proliferation and Wnt pathway in lung cancer cells. Black-Right-Pointing-Pointer shRNA knock-down of Fzd-8 suppresses tumor growth in vivo. Black-Right-Pointing-Pointer shRNA knock-down Fzd-8 sensitizes lung cancer cells to chemotherapy Taxotere. -- Abstract: Lung cancer is the leading cause of cancer related deaths worldwide. It is necessary to better understand the molecular mechanisms involved in lung cancer in order to develop more effective therapeutics for the treatment of this disease. Recent reports have shown that Wnt signaling pathway is important in a number of cancer types including lung cancer. However, the role of Frizzled-8 (Fzd-8), one of the Frizzled family of receptors for the Wnt ligands, in lung cancer still remains to be elucidated. Here in this study we showed that Fzd-8 was over-expressed in human lung cancer tissue samples and cell lines. To investigate the functional importance of the Fzd-8 over-expression in lung cancer, we used shRNA to knock down Fzd-8 mRNA in lung cancer cells expressing the gene. We observed that Fzd-8 shRNA inhibited cell proliferation along with decreased activity of Wnt pathway in vitro, and also significantly suppressed A549 xenograft model in vivo (p < 0.05). Furthermore, we found that knocking down Fzd-8 by shRNA sensitized the lung cancer cells to chemotherapy Taxotere. These data suggest that Fzd-8 is a putative therapeutic target for human lung cancer and over-expression of Fzd-8 may be important for aberrant Wnt activation in lung cancer.

  20. Smarter finance for cleaner energy: open up master limited partnerships (MLPs) and real estate investment trusts (REITs) to renewable energy investment

    SciTech Connect (OSTI)

    Mormann, Feliz; Reicher, Dan

    2012-11-15

    Master Limited Partnerships (MLPs) and Real Estate Investment Trusts (REITs)—both well-established investment structures—should be opened up to renewable energy investment. MLPs and, more recently, REITs have a proven track record for promoting oil, gas, and other traditional energy sources. When extended to renewable energy projects these tools will help promote growth, move renewables closer to subsidy independence, and vastly broaden the base of investors in America’s energy economy. The extension of MLPs and REITs to renewables enjoys significant support from the investment and clean energy communities. In addition, MLPs for renewables also enjoy bipartisan political backing in Congress.

  1. Predicting Pneumonitis Risk: A Dosimetric Alternative to Mean Lung Dose

    SciTech Connect (OSTI)

    Tucker, Susan L.; Mohan, Radhe; Liengsawangwong, Raweewan; Martel, Mary K.; Liao Zhongxing

    2013-02-01

    Purpose: To determine whether the association between mean lung dose (MLD) and risk of severe (grade {>=}3) radiation pneumonitis (RP) depends on the dose distribution pattern to normal lung among patients receiving 3-dimensional conformal radiation therapy for non-small-cell lung cancer. Methods and Materials: Three cohorts treated with different beam arrangements were identified. One cohort (2-field boost [2FB]) received 2 parallel-opposed (anteroposterior-posteroanterior) fields per fraction initially, followed by a sequential boost delivered using 2 oblique beams. The other 2 cohorts received 3 or 4 straight fields (3FS and 4FS, respectively), ie, all fields were irradiated every day. The incidence of severe RP was plotted against MLD in each cohort, and data were analyzed using the Lyman-Kutcher-Burman (LKB) model. Results: The incidence of grade {>=}3 RP rose more steeply as a function of MLD in the 2FB cohort (N=120) than in the 4FS cohort (N=138), with an intermediate slope for the 3FS group (N=99). The estimated volume parameter from the LKB model was n=0.41 (95% confidence interval, 0.15-1.0) and led to a significant improvement in fit (P=.05) compared to a fit with volume parameter fixed at n=1 (the MLD model). Unlike the MLD model, the LKB model with n=0.41 provided a consistent description of the risk of severe RP in all three cohorts (2FB, 3FS, 4FS) simultaneously. Conclusions: When predicting risk of grade {>=}3 RP, the mean lung dose does not adequately take into account the effects of high doses. Instead, the effective dose, computed from the LKB model using volume parameter n=0.41, may provide a better dosimetric parameter for predicting RP risk. If confirmed, these findings support the conclusion that for the same MLD, high doses to small lung volumes ('a lot to a little') are worse than low doses to large volumes ('a little to a lot').

  2. Molecular Markers of Lung Cancer in MAYAK Workers

    SciTech Connect (OSTI)

    Steven A. Belinsky, PhD

    2007-02-15

    The molecular mechanisms that result in the elevated risk for lung cancer associated with exposure to radiation have not been well characterized. Workers from the MAYAK nuclear enterprise are an ideal cohort in which to study the molecular epidemiology of cancer associated with radiation exposure and to identify the genes targeted for inactivation that in turn affect individual risk for radiation-induced lung cancer. Epidemiology studies of the MAYAK cohort indicate a significantly higher frequency for adenocarcinoma and squamous cell carcinoma (SCC) in workers than in a control population and a strong correlation between these tumor types and plutonium exposure. Two hypotheses will be evaluated through the proposed studies. First, radiation exposure targets specific genes for inactivation by promoter methylation. This hypothesis is supported by our recent studies with the MAYAK population that demonstrated the targeting of the p16 gene for inactivation by promoter methylation in adenocarcinomas from workers (1). Second, genes inactivated in tumors can serve as biomarkers for lung cancer risk in a cancer-free population of workers exposed to plutonium. Support for this hypothesis is based on exciting preliminary results of our nested, case-control study of persons from the Colorado cohort. In that study, a panel of methylation markers for predicting lung cancer risk is being evaluated in sputum samples from incident lung cancer cases and controls. The first hypothesis will be tested by determining the prevalence for promoter hypermethylation of a panel of genes shown to play a critical role in the development of either adenocarcinoma and/or SCC associated with tobacco. Our initial studies on adenocarcinoma in MAYAK workers will be extended to evaluate methylation of the PAX5 {alpha}, PAX5 {beta}, H-cadherin, GATA5, and bone morphogenesis 3B (BMP3B) genes in the original sample set described under Preliminary studies. In addition, studies will be initiated in SCC from workers and controls to identify genes targeted for inactivation by plutonium in this other common histologic form of lung cancer. We will examine methylation of the p16, O{sup 6}-methylguanine-DNA methyl-transferase (MGMT), and death associated protein kinase genes ([DAP-K], evaluated previously in adenocarcinomas) as well as the new genes being assessed in the adenocarcinomas. The second hypothesis will be tested in a cross-sectional study of cancer-free workers exposed to plutonium and an unexposed population. A cohort of 700 cancer-free workers and 700 unexposed persons is being assembled, exposures are being defined, and induced sputum collected at initial entry into the study and approximately 1-year later. Exposed and unexposed persons will be matched by 5-year age intervals and smoking status (current and former). The frequency for methylation of four genes that show the greatest difference in prevalence in tumors from workers and controls will be determined in exfoliated cells within sputum. These studies will extend those in primary tumors to determine whether difference in prevalence for individual or multiple genes are detected in sputum samples from high-risk subjects exposed to plutonium. Follow-up of this cohort offers the opportunity to validate these endpoints and future biomarkers as true markers for lung cancer risk.

  3. Correlation of Clinical and Dosimetric Factors With Adverse Pulmonary Outcomes in Children After Lung Irradiation

    SciTech Connect (OSTI)

    Venkatramani, Rajkumar; Kamath, Sunil; Wong, Kenneth; Malvar, Jemily; Sposto, Richard; Goodarzian, Fariba; Freyer, David R.; Keens, Thomas G.; and others

    2013-08-01

    Purpose: To identify the incidence and the risk factors for pulmonary toxicity in children treated for cancer with contemporary lung irradiation. Methods and Materials: We analyzed clinical features, radiographic findings, pulmonary function tests, and dosimetric parameters of children receiving irradiation to the lung fields over a 10-year period. Results: We identified 109 patients (75 male patients). The median age at irradiation was 13.8 years (range, 0.04-20.9 years). The median follow-up period was 3.4 years. The median prescribed radiation dose was 21 Gy (range, 0.4-64.8 Gy). Pulmonary toxic chemotherapy included bleomycin in 58.7% of patients and cyclophosphamide in 83.5%. The following pulmonary outcomes were identified and the 5-year cumulative incidence after irradiation was determined: pneumonitis, 6%; chronic cough, 10%; pneumonia, 35%; dyspnea, 11%; supplemental oxygen requirement, 2%; radiographic interstitial lung disease, 40%; and chest wall deformity, 12%. One patient died of progressive respiratory failure. Post-irradiation pulmonary function tests available from 44 patients showed evidence of obstructive lung disease (25%), restrictive disease (11%), hyperinflation (32%), and abnormal diffusion capacity (12%). Thoracic surgery, bleomycin, age, mean lung irradiation dose (MLD), maximum lung dose, prescribed dose, and dosimetric parameters between V{sub 22} (volume of lung exposed to a radiation dose ≥22 Gy) and V{sub 30} (volume of lung exposed to a radiation dose ≥30 Gy) were significant for the development of adverse pulmonary outcomes on univariate analysis. MLD, maximum lung dose, and V{sub dose} (percentage of volume of lung receiving the threshold dose or greater) were highly correlated. On multivariate analysis, MLD was the sole significant predictor of adverse pulmonary outcome (P=.01). Conclusions: Significant pulmonary dysfunction occurs in children receiving lung irradiation by contemporary techniques. MLD rather than prescribed dose should be used to perform risk stratification of patients receiving lung irradiation.

  4. Sustainable Energy Trust Fund

    Broader source: Energy.gov [DOE]

    The SETF is financed by a non-bypassable surcharge on the electric and natural gas bills of utility customers who are not Residential Aid Discount (RAD) or Residential Essential Service (RES)...

  5. Energy Efficiency Trust Fund

    Broader source: Energy.gov [DOE]

    Additional funds may be accumulated through non-compliance fees as part of the Energy Efficiency Portfolio Standard (EEPS). For both natural gas and electric utilities, failure to submit an energ...

  6. Energy Trust of Oregon

    Broader source: Energy.gov [DOE]

    Of the funds collected by the electric utilities, 56.7% must be allocated towards energy efficiency programs and 17.1% to renewables. The remaining funds support low-income housing energy...

  7. H. R. 460: A Bill to amend the Internal Revenue Code of 1986 to reinstate the windfall profit tax on domestic crude oil and to appropriate the proceeds of the tax to the Resolution Trust Corporation, introduced in the House of Representatives, One Hundred Second Congress, First Session, January 7, 1991

    SciTech Connect (OSTI)

    Not Available

    1991-01-01

    The bill describes changes to the Internal Revenue Code under the following headings: reinstatement of windfall profit tax on domestic crude oil; termination of tax linked to existence of Resolution Trust Corporation; modification of category of newly discovered oil; conforming amendments; effective date; and revenues from windfall profit tax to be used by Resolution Trust Corporation.

  8. A multiscale MDCT image-based breathing lung model with time-varying regional ventilation

    SciTech Connect (OSTI)

    Yin, Youbing, E-mail: youbing-yin@uiowa.edu [Department of Mechanical and Industrial Engineering, The University of Iowa, Iowa City, IA 52242 (United States) [Department of Mechanical and Industrial Engineering, The University of Iowa, Iowa City, IA 52242 (United States); IIHR-Hydroscience and Engineering, The University of Iowa, Iowa City, IA 52242 (United States); Department of Radiology, The University of Iowa, Iowa City, IA 52242 (United States); Choi, Jiwoong, E-mail: jiwoong-choi@uiowa.edu [Department of Mechanical and Industrial Engineering, The University of Iowa, Iowa City, IA 52242 (United States) [Department of Mechanical and Industrial Engineering, The University of Iowa, Iowa City, IA 52242 (United States); IIHR-Hydroscience and Engineering, The University of Iowa, Iowa City, IA 52242 (United States); Hoffman, Eric A., E-mail: eric-hoffman@uiowa.edu [Department of Radiology, The University of Iowa, Iowa City, IA 52242 (United States); Department of Biomedical Engineering, The University of Iowa, Iowa City, IA 52242 (United States); Department of Internal Medicine, The University of Iowa, Iowa City, IA 52242 (United States); Tawhai, Merryn H., E-mail: m.tawhai@auckland.ac.nz [Auckland Bioengineering Institute, The University of Auckland, Auckland (New Zealand); Lin, Ching-Long, E-mail: ching-long-lin@uiowa.edu [Department of Mechanical and Industrial Engineering, The University of Iowa, Iowa City, IA 52242 (United States) [Department of Mechanical and Industrial Engineering, The University of Iowa, Iowa City, IA 52242 (United States); IIHR-Hydroscience and Engineering, The University of Iowa, Iowa City, IA 52242 (United States)

    2013-07-01

    A novel algorithm is presented that links local structural variables (regional ventilation and deforming central airways) to global function (total lung volume) in the lung over three imaged lung volumes, to derive a breathing lung model for computational fluid dynamics simulation. The algorithm constitutes the core of an integrative, image-based computational framework for subject-specific simulation of the breathing lung. For the first time, the algorithm is applied to three multi-detector row computed tomography (MDCT) volumetric lung images of the same individual. A key technique in linking global and local variables over multiple images is an in-house mass-preserving image registration method. Throughout breathing cycles, cubic interpolation is employed to ensure C{sub 1} continuity in constructing time-varying regional ventilation at the whole lung level, flow rate fractions exiting the terminal airways, and airway deformation. The imaged exit airway flow rate fractions are derived from regional ventilation with the aid of a three-dimensional (3D) and one-dimensional (1D) coupled airway tree that connects the airways to the alveolar tissue. An in-house parallel large-eddy simulation (LES) technique is adopted to capture turbulent-transitional-laminar flows in both normal and deep breathing conditions. The results obtained by the proposed algorithm when using three lung volume images are compared with those using only one or two volume images. The three-volume-based lung model produces physiologically-consistent time-varying pressure and ventilation distribution. The one-volume-based lung model under-predicts pressure drop and yields un-physiological lobar ventilation. The two-volume-based model can account for airway deformation and non-uniform regional ventilation to some extent, but does not capture the non-linear features of the lung.

  9. Effects of coal combustion and gasification upon lung structure and function. Quarterly progress report

    SciTech Connect (OSTI)

    Hinton, Dr., David E.

    1980-12-12

    The effects on lungs of emissions from fluidized-bed combustion and coal gasification on man are being studied by inhalation experiments and intratracheal administration of fly ash to hamsters. The hamsters are sacrificed at 1, 3, 6, 9 and 30 days and the lungs examined by methods which are described. (LTN)

  10. 2D/3D registration algorithm for lung brachytherapy

    SciTech Connect (OSTI)

    Zvonarev, P. S.; Farrell, T. J.; Hunter, R.; Wierzbicki, M.; Hayward, J. E.; Sur, R. K.

    2013-02-15

    Purpose: A 2D/3D registration algorithm is proposed for registering orthogonal x-ray images with a diagnostic CT volume for high dose rate (HDR) lung brachytherapy. Methods: The algorithm utilizes a rigid registration model based on a pixel/voxel intensity matching approach. To achieve accurate registration, a robust similarity measure combining normalized mutual information, image gradient, and intensity difference was developed. The algorithm was validated using a simple body and anthropomorphic phantoms. Transfer catheters were placed inside the phantoms to simulate the unique image features observed during treatment. The algorithm sensitivity to various degrees of initial misregistration and to the presence of foreign objects, such as ECG leads, was evaluated. Results: The mean registration error was 2.2 and 1.9 mm for the simple body and anthropomorphic phantoms, respectively. The error was comparable to the interoperator catheter digitization error of 1.6 mm. Preliminary analysis of data acquired from four patients indicated a mean registration error of 4.2 mm. Conclusions: Results obtained using the proposed algorithm are clinically acceptable especially considering the complications normally encountered when imaging during lung HDR brachytherapy.

  11. Receptor tyrosine kinase EphA5 is a functional molecular target in human lung cancer

    SciTech Connect (OSTI)

    Staquicini, Fernanda I.; Qian, Ming D.; Salameh, Ahmad; Dobroff, Andrey S.; Edwards, Julianna K.; Cimino, Daniel F.; Moeller, Benjamin J.; Kelly, Patrick; Nunez, Maria I.; Tang, Ximing; Liu, Diane D.; Lee, J. Jack; Hong, Waun Ki; Ferrara, Fortunato; Bradbury, Andrew R. M.; Lobb, Roy R.; Edelman, Martin J.; Sidman, Richard L.; Wistuba, Ignacio I.; Arap, Wadih; Pasqualini, Renata

    2015-03-20

    Lung cancer is often refractory to radiotherapy, but molecular mechanisms of tumor resistance remain poorly defined. Here we show that the receptor tyrosine kinase EphA5 is specifically overexpressed in lung cancer and is involved in regulating cellular responses to genotoxic insult. In the absence of EphA5, lung cancer cells displayed a defective G1/S cell cycle checkpoint, were unable to resolve DNA damage, and became radiosensitive. Upon irradiation, EphA5 was transported into the nucleus where it interacted with activated ATM (ataxia-telangiectasia mutated) at sites of DNA repair. In conclusion, we demonstrate that a new monoclonal antibody against human EphA5 sensitized lung cancer cells and human lung cancer xenografts to radiotherapy and significantly prolonged survival, thus suggesting the likelihood of translational applications.

  12. Cellular morphometry of the bronchi of human and dog lungs

    SciTech Connect (OSTI)

    Robbins, E.S.

    1992-09-01

    Quantitative data of the human bronchial epithelial cells at possible risk for malignant transformation in lung cancer is crucial for accurate radon dosimetry and risk analysis. The locations and other parameters of the nuclei which may be damaged by [alpha] particles must be determined and compared in different airway generations, among smokers, non-smokers and ex-smokers, between men and women and in people of different ages. This proposal includes extended morphometric studies on electron micrographs of human epithelium of defined airway generations and in parallel on electron micrographs of the dog bronchial lining. The second part of this proposal describes studies to quantitate the cycling bronchial epithelial population(s) using proliferation markers and immunocytochemistry on frozen and paraffin sections and similar labeling of isolated bronchial epithelial cells sorted flow cytometry.

  13. SU-E-J-190: Characterization of Radiation Induced CT Number Changes in Tumor and Normal Lung During Radiation Therapy for Lung Cancer

    SciTech Connect (OSTI)

    Yang, C; Liu, F; Tai, A; Gore, E; Johnstone, C; Li, X

    2014-06-01

    Purpose: To measure CT number (CTN) changes in tumor and normal lung as a function of radiation therapy (RT) dose during the course of RT delivery for lung cancer using daily IGRT CT images and single respiration phase CT images. Methods: 4D CT acquired during planning simulation and daily 3D CT acquired during daily IGRT for 10 lung cancer cases randomly selected in terms of age, caner type and stage, were analyzed using an in-house developed software tool. All patients were treated in 2 Gy fractions to primary tumors and involved nodal regions. Regions enclosed by a series of isodose surfaces in normal lung were delineated. The obtained contours along with target contours (GTVs) were populated to each singlephase planning CT and daily CT. CTN in term of Hounsfield Unit (HU) of each voxel in these delineated regions were collectively analyzed using histogram, mean, mode and linear correlation. Results: Respiration induced normal lung CTN change, as analyzed from single-phase planning CTs, ranged from 9 to 23 (2) HU for the patients studied. Normal lung CTN change was as large as 50 (12) HU over the entire treatment course, was dose and patient dependent and was measurable with dose changes as low as 1.5 Gy. For patients with obvious tumor volume regression, CTN within the GTV drops monotonically as much as 10 (1) HU during the early fractions with a total dose of 20 Gy delivered. The GTV and CTN reductions are significantly correlated with correlation coefficient >0.95. Conclusion: Significant RT dose induced CTN changes in lung tissue and tumor region can be observed during even the early phase of RT delivery, and may potentially be used for early prediction of radiation response. Single respiration phase CT images have dramatically reduced statistical noise in ROIs, making daily dose response evaluation possible.

  14. Role of reactive nitrogen species generated via inducible nitric oxide synthase in vesicant-induced lung injury, inflammation and altered lung functioning

    SciTech Connect (OSTI)

    Sunil, Vasanthi R.; Shen, Jianliang; Patel-Vayas, Kinal; Gow, Andrew J.; Laskin, Jeffrey D.; Laskin, Debra L.

    2012-05-15

    Pulmonary toxicity induced by sulfur mustard and related vesicants is associated with oxidative stress. In the present studies we analyzed the role of reactive nitrogen species (RNS) generated via inducible nitric oxide synthase (iNOS) in lung injury and inflammation induced by vesicants using 2-chloroethyl ethyl sulfide (CEES) as a model. C57Bl/6 (WT) and iNOS ?/? mice were sacrificed 3 days or 14 days following intratracheal administration of CEES (6 mg/kg) or control. CEES intoxication resulted in transient (3 days) increases in bronchoalveolar lavage (BAL) cell and protein content in WT, but not iNOS ?/? mice. This correlated with expression of Ym1, a marker of oxidative stress in alveolar macrophages and epithelial cells. In contrast, in iNOS ?/? mice, Ym1 was only observed 14 days post-exposure in enlarged alveolar macrophages, suggesting that they are alternatively activated. This is supported by findings that lung tumor necrosis factor and lipocalin Lcn2 expression, mediators involved in tissue repair were also upregulated at this time in iNOS ?/? mice. Conversely, CEES-induced increases in the proinflammatory genes, monocyte chemotactic protein-1 and cyclooxygenase-2, were abrogated in iNOS ?/? mice. In WT mice, CEES treatment also resulted in increases in total lung resistance and decreases in compliance in response to methacholine, effects blunted by loss of iNOS. These data demonstrate that RNS, generated via iNOS play a role in the pathogenic responses to CEES, augmenting oxidative stress and inflammation and suppressing tissue repair. Elucidating inflammatory mechanisms mediating vesicant-induced lung injury is key to the development of therapeutics to treat mustard poisoning. -- Highlights: ? Lung injury, inflammation and oxidative stress are induced by the model vesicant CEES ? RNS generated via iNOS are important in the CEES-induced pulmonary toxicity ? iNOS ?/? mice are protected from CEES-induced lung toxicity and altered lung functioning.

  15. H-1 Nuclear Magnetic Resonance Metabolomics Analysis Identifies Novel Urinary Biomarkers for Lung Function

    SciTech Connect (OSTI)

    MCClay, Joseph L.; Adkins, Daniel E.; Isern, Nancy G.; O'Connell, Thomas M.; Wooten, Jan B.; Zedler, Barbara K.; Dasika, Madhukar S.; Webb, B. T.; Webb-Robertson, Bobbie-Jo M.; Pounds, Joel G.; Murrelle, Edward L.; Leppert, Mark F.; van den Oord, Edwin J.

    2010-06-04

    Chronic obstructive pulmonary disease (COPD), characterized by chronic airflow limitation, is a serious and growing public health concern. The major environmental risk factor for COPD is tobacco smoking, but the biological mechanisms underlying COPD are not well understood. In this study, we used proton nuclear magnetic resonance (1H-NMR) spectroscopy to identify and quantify metabolites associated with lung function in COPD. Plasma and urine were collected from 197 adults with COPD and from 195 adults without COPD. Samples were assayed using a 600 MHz NMR spectrometer, and the resulting spectra were analyzed against quantitative spirometric measures of lung function. After correcting for false discoveries and adjusting for covariates (sex, age, smoking) several spectral regions in urine were found to be significantly associated with baseline lung function. These regions correspond to the metabolites trigonelline, hippurate and formate. Concentrations of each metabolite, standardized to urinary creatinine, were associated with baseline lung function (minimum p-value = 0.0002 for trigonelline). No significant associations were found with plasma metabolites. Two of the three urinary metabolites positively associated with baseline lung function, i.e. hippurate and formate, are often related to gut microflora. This suggests that the microbiome composition is variable between individuals with different lung function. Alternatively, the nature and origins of all three associated metabolites may reflect lifestyle differences affecting overall health. Our results will require replication and validation, but demonstrate the utility of NMR metabolomics as a screening tool for identifying novel biomarkers of lung disease or disease risk.

  16. The cough response to ultrasonically nebulized distilled water in heart-lung transplantation patients

    SciTech Connect (OSTI)

    Higenbottam, T.; Jackson, M.; Woolman, P.; Lowry, R.; Wallwork, J.

    1989-07-01

    As a result of clinical heart-lung transplantation, the lungs are denervated below the level of the tracheal anastomosis. It has been questioned whether afferent vagal reinnervation occurs after surgery. Here we report the cough frequency, during inhalation of ultrasonically nebulized distilled water, of 15 heart-lung transplant patients studied 6 wk to 36 months after surgery. They were compared with 15 normal subjects of a similar age and sex. The distribution of the aerosol was studied in five normal subjects using /sup 99m/technetium diethylene triamine pentaacetate (/sup 99m/Tc-DTPA) in saline. In seven patients, the sensitivity of the laryngeal mucosa to instilled distilled water (0.2 ml) was tested at the time of fiberoptic bronchoscopy by recording the cough response. Ten percent of the aerosol was deposited onto the larynx and trachea, 56% on the central airways, and 34% in the periphery of the lung. The cough response to the aerosol was strikingly diminished in the patients compared with normal subjects (p less than 0.001), but all seven patients coughed when distilled water was instilled onto the larynx. As expected, the laryngeal mucosa of heart-lung transplant patients remains sensitive to distilled water. However, the diminished coughing when the distilled water is distributed by aerosol to the central airways supports the view that vagal afferent nerves do not reinnervate the lungs after heart-lung transplantation, up to 36 months after surgery.

  17. Iron supplementation at high altitudes induces inflammation and oxidative injury to lung tissues in rats

    SciTech Connect (OSTI)

    Salama, Samir A.; Omar, Hany A.; Maghrabi, Ibrahim A.; AlSaeed, Mohammed S.; EL-Tarras, Adel E.

    2014-01-01

    Exposure to high altitudes is associated with hypoxia and increased vulnerability to oxidative stress. Polycythemia (increased number of circulating erythrocytes) develops to compensate the high altitude associated hypoxia. Iron supplementation is, thus, recommended to meet the demand for the physiological polycythemia. Iron is a major player in redox reactions and may exacerbate the high altitudes-associated oxidative stress. The aim of this study was to explore the potential iron-induced oxidative lung tissue injury in rats at high altitudes (6000 ft above the sea level). Iron supplementation (2 mg elemental iron/kg, once daily for 15 days) induced histopathological changes to lung tissues that include severe congestion, dilatation of the blood vessels, emphysema in the air alveoli, and peribronchial inflammatory cell infiltration. The levels of pro-inflammatory cytokines (IL-1?, IL-6, and TNF-?), lipid peroxidation product and protein carbonyl content in lung tissues were significantly elevated. Moreover, the levels of reduced glutathione and total antioxidant capacity were significantly reduced. Co-administration of trolox, a water soluble vitamin E analog (25 mg/kg, once daily for the last 7 days of iron supplementation), alleviated the lung histological impairments, significantly decreased the pro-inflammatory cytokines, and restored the oxidative stress markers. Together, our findings indicate that iron supplementation at high altitudes induces lung tissue injury in rats. This injury could be mediated through excessive production of reactive oxygen species and induction of inflammatory responses. The study highlights the tissue injury induced by iron supplementation at high altitudes and suggests the co-administration of antioxidants such as trolox as protective measures. - Highlights: Iron supplementation at high altitudes induced lung histological changes in rats. Iron induced oxidative stress in lung tissues of rats at high altitudes. Iron increased the levels of IL-1?, IL-6 and TNF-? in lung tissues at high altitudes. Trolox alleviated the iron-induced histological and biochemical changes to the lungs.

  18. Real-Time Tumor Tracking in the Lung Using an Electromagnetic Tracking System

    SciTech Connect (OSTI)

    Shah, Amish P.; Kupelian, Patrick A.; Waghorn, Benjamin J.; Willoughby, Twyla R.; Rineer, Justin M.; Maon, Rafael R.; Vollenweider, Mark A.; Meeks, Sanford L.

    2013-07-01

    Purpose: To describe the first use of the commercially available Calypso 4D Localization System in the lung. Methods and Materials: Under an institutional review board-approved protocol and an investigational device exemption from the US Food and Drug Administration, the Calypso system was used with nonclinical methods to acquire real-time 4-dimensional lung tumor tracks for 7 lung cancer patients. The aims of the study were to investigate (1) the potential for bronchoscopic implantation; (2) the stability of smooth-surface beacon transponders (transponders) after implantation; and (3) the ability to acquire tracking information within the lung. Electromagnetic tracking was not used for any clinical decision making and could only be performed before any radiation delivery in a research setting. All motion tracks for each patient were reviewed, and values of the average displacement, amplitude of motion, period, and associated correlation to a sinusoidal model (R{sup 2}) were tabulated for all 42 tracks. Results: For all 7 patients at least 1 transponder was successfully implanted. To assist in securing the transponder at the tumor site, it was necessary to implant a secondary fiducial for most transponders owing to the transponder's smooth surface. For 3 patients, insertion into the lung proved difficult, with only 1 transponder remaining fixed during implantation. One patient developed a pneumothorax after implantation of the secondary fiducial. Once implanted, 13 of 14 transponders remained stable within the lung and were successfully tracked with the tracking system. Conclusions: Our initial experience with electromagnetic guidance within the lung demonstrates that transponder implantation and tracking is achievable though not clinically available. This research investigation proved that lung tumor motion exhibits large variations from fraction to fraction within a single patient and that improvements to both transponder and tracking system are still necessary to create a clinical daily-use system to assist with actual lung radiation therapy.

  19. Determination of In-Vitro Lung Solubility and Intake-To-Dose Conversion

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Factors for Tritiated LaNi4.25Al0.75 Hydride | Department of Energy Determination of In-Vitro Lung Solubility and Intake-To-Dose Conversion Factors for Tritiated LaNi4.25Al0.75 Hydride Determination of In-Vitro Lung Solubility and Intake-To-Dose Conversion Factors for Tritiated LaNi4.25Al0.75 Hydride Presentation from the 34th Tritium Focus Group Meeting held in Idaho Falls, Idaho on September 23-25, 2014. PDF icon Determination of In-Vitro Lung Solubility and Intake-To-Dose Conversion

  20. Low-Dose Spiral CT Scans for Early Lung Cancer Detection

    Broader source: Energy.gov [DOE]

    Low-dose spiral computed tomography (CT) scanning is a noninvasive medical imaging test that has been used for the early detection of lung cancer for over 16 years (Sone et al. 1998; Henschke et.al. 1999).

  1. Determination of In-Vitro Lung Solubility and Intake-To-Dose...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Presentation from the 34th Tritium Focus Group Meeting held in Idaho Falls, Idaho on September 23-25, 2014. PDF icon Determination of In-Vitro Lung Solubility and Intake-To-Dose ...

  2. Toward in vivo lung's tissue incompressibility characterization for tumor motion modeling in radiation therapy

    SciTech Connect (OSTI)

    Shirzadi, Zahra; Sadeghi-Naini, Ali; Samani, Abbas

    2013-05-15

    Purpose: A novel technique is proposed to characterize lung tissue incompressibility variation during respiration. Estimating lung tissue incompressibility parameter variations resulting from air content variation throughout respiration is critical for computer assisted tumor motion tracking. Continuous tumor motion is a major challenge in lung cancer radiotherapy, especially with external beam radiotherapy. If not accounted for, this motion may lead to areas of radiation overdosage for normal tissue. Given the unavailability of imaging modality that can be used effectively for real-time lung tumor tracking, computer assisted approach based on tissue deformation estimation can be a good alternative. This approach involves lung biomechanical model where its fidelity depends on input tissue properties. This investigation shows that considering variable tissue incompressibility parameter is very important for predicting tumor motion accurately, hence improving the lung radiotherapy outcome. Methods: First, an in silico lung phantom study was conducted to demonstrate the importance of employing variable Poisson's ratio for tumor motion predication. After it was established that modeling this variability is critical for accurate tumor motion prediction, an optimization based technique was developed to estimate lung tissue Poisson's ratio as a function of respiration cycle time. In this technique, the Poisson's ratio and lung pressure value were varied systematically until optimal values were obtained, leading to maximum similarity between acquired and simulated 4D CT lung images. This technique was applied in an ex vivo porcine lung study where simulated images were constructed using the end exhale CT image and deformation fields obtained from the lung's FE modeling of each respiration time increment. To model the tissue, linear elastic and Marlow hyperelastic material models in conjunction with variable Poisson's ratio were used. Results: The phantom study showed that the tumor motion trajectory and its final locations obtained from simulations with and without considering tissue incompressibility variation were very different. For example, tumor displacements in the z direction were -11.23 and -38.10 mm obtained with the Marlow hyperelastic material model in conjunction with constant and variable Poisson's ratio, respectively. By comparing the acquired 4D-CT image sequence of the porcine lung with their image sequence counterparts obtained from the hyperelastic model with constant and variable Poisson's ratio, it was shown that using variable tissue incompressibility reduced errors significantly in tumor motion prediction. Conclusions: This investigation demonstrates the importance of incompressibility variation estimation and utilization for accurate tumor tracking in computer assisted lung external beam radiation therapy. An optimization framework was developed to estimate a Poisson's ratio function in terms of respiration cycle time using experimental image data of the lung. Utilizing this function along with respiratory system FE modeling may lead to more effective tumor targeting, hence potentially improving the outcome of lung external beam radiation therapy techniques. This is particularly true for stereotactic body radiation therapy where only one or a few fraction treatments are applied, precluding the possibility of averaging out dosimetric deviations introduced by the respiratory motion.

  3. Respiratory symptoms and lung function in oil mist-exposed workers

    SciTech Connect (OSTI)

    Jarvholm, B.; Bake, B.; Lavenius, B.; Thiringer, G.; Vokmann, R.

    1982-06-01

    The prevalence of respiratory symptoms was registered and ventilatory function was determined in 164 men exposed to oil mist. The average exposure time was 16.2 years. One hundred fifty-nine office workers served as controls. The exposed men reported more respiratory symptoms: 14% of the exposed nonsmokers v. 2% of the nonsmoking controls having cough at least three months a year. There were non significant differences between spirometric measurements and chest roentgenograms of the men exposed to oil mist and those of the office workers. The lung function of 25 nonsmoking exposed men was further examined with other lung function tests. The mean values for closing volume, slope of the alveolar plateau, total lung capacity, residual volume, elastic recoil at various lung volumes, and diffusion capacity did not differ significantly.

  4. Receptor tyrosine kinase EphA5 is a functional molecular target in human lung cancer

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Staquicini, Fernanda I.; Qian, Ming D.; Salameh, Ahmad; Dobroff, Andrey S.; Edwards, Julianna K.; Cimino, Daniel F.; Moeller, Benjamin J.; Kelly, Patrick; Nunez, Maria I.; Tang, Ximing; et al

    2015-03-20

    Lung cancer is often refractory to radiotherapy, but molecular mechanisms of tumor resistance remain poorly defined. Here we show that the receptor tyrosine kinase EphA5 is specifically overexpressed in lung cancer and is involved in regulating cellular responses to genotoxic insult. In the absence of EphA5, lung cancer cells displayed a defective G1/S cell cycle checkpoint, were unable to resolve DNA damage, and became radiosensitive. Upon irradiation, EphA5 was transported into the nucleus where it interacted with activated ATM (ataxia-telangiectasia mutated) at sites of DNA repair. In conclusion, we demonstrate that a new monoclonal antibody against human EphA5 sensitized lungmore » cancer cells and human lung cancer xenografts to radiotherapy and significantly prolonged survival, thus suggesting the likelihood of translational applications.« less

  5. H. R. 3737: A Bill to amend the Internal Revenue Code of 1986 to impose an excise tax on certain uses of virgin materials and to establish a trust fund for recycling assistance and solid waste management planning. Introduced in the House of Representatives, One Hundredth First Congress, First Session, November 19, 1989

    SciTech Connect (OSTI)

    Not Available

    1989-01-01

    H.R. 3737 is a bill to amend the Internal Revenue Code of 1986 to impose an excise tax on certain uses of virgin materials and to establish a trust fund for recycling assistance and solid waste management planning.

  6. Large scale validation of the M5L lung CAD on heterogeneous CT datasets

    SciTech Connect (OSTI)

    Lopez Torres, E. E-mail: cerello@to.infn.it; Fiorina, E.; Pennazio, F.; Peroni, C.; Saletta, M.; Cerello, P. E-mail: cerello@to.infn.it; Camarlinghi, N.; Fantacci, M. E.

    2015-04-15

    Purpose: M5L, a fully automated computer-aided detection (CAD) system for the detection and segmentation of lung nodules in thoracic computed tomography (CT), is presented and validated on several image datasets. Methods: M5L is the combination of two independent subsystems, based on the Channeler Ant Model as a segmentation tool [lung channeler ant model (lungCAM)] and on the voxel-based neural approach. The lungCAM was upgraded with a scan equalization module and a new procedure to recover the nodules connected to other lung structures; its classification module, which makes use of a feed-forward neural network, is based of a small number of features (13), so as to minimize the risk of lacking generalization, which could be possible given the large difference between the size of the training and testing datasets, which contain 94 and 1019 CTs, respectively. The lungCAM (standalone) and M5L (combined) performance was extensively tested on 1043 CT scans from three independent datasets, including a detailed analysis of the full Lung Image Database Consortium/Image Database Resource Initiative database, which is not yet found in literature. Results: The lungCAM and M5L performance is consistent across the databases, with a sensitivity of about 70% and 80%, respectively, at eight false positive findings per scan, despite the variable annotation criteria and acquisition and reconstruction conditions. A reduced sensitivity is found for subtle nodules and ground glass opacities (GGO) structures. A comparison with other CAD systems is also presented. Conclusions: The M5L performance on a large and heterogeneous dataset is stable and satisfactory, although the development of a dedicated module for GGOs detection could further improve it, as well as an iterative optimization of the training procedure. The main aim of the present study was accomplished: M5L results do not deteriorate when increasing the dataset size, making it a candidate for supporting radiologists on large scale screenings and clinical programs.

  7. Lung Toxicity and Mutagenicity of Emissions From Heavy-Duty Compressed

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Natural Gas (CNG)-Powered Vehicles | Department of Energy Lung Toxicity and Mutagenicity of Emissions From Heavy-Duty Compressed Natural Gas (CNG)-Powered Vehicles Lung Toxicity and Mutagenicity of Emissions From Heavy-Duty Compressed Natural Gas (CNG)-Powered Vehicles 2005 Diesel Engine Emissions Reduction (DEER) Conference Presentations and Posters PDF icon 2005_deer_mauderly.pdf More Documents & Publications Relationship Between Composition and Toxicity of Engine Emission Samples

  8. Radiotherapy in Small-Cell Lung Cancer: Lessons Learned and Future Directions

    SciTech Connect (OSTI)

    Slotman, Ben J.; Senan, Suresh

    2011-03-15

    Although chemotherapy is an essential component in the treatment of small-cell lung cancer, improvements in survival in the past two decades have been mainly achieved by the appropriate application of radiotherapy. The aim of the present study was to review the key developments in thoracic radiotherapy and prophylactic cranial radiotherapy and to discuss the rationale behind key ongoing studies in small-cell lung cancer.

  9. Structures of Lung Cancer-Derived EGFR Mutants and Inhibitor Complexes:

    Office of Scientific and Technical Information (OSTI)

    Mechanism of Activation and Insights into Differential Inhibitor Sensitivity (Journal Article) | SciTech Connect Structures of Lung Cancer-Derived EGFR Mutants and Inhibitor Complexes: Mechanism of Activation and Insights into Differential Inhibitor Sensitivity Citation Details In-Document Search Title: Structures of Lung Cancer-Derived EGFR Mutants and Inhibitor Complexes: Mechanism of Activation and Insights into Differential Inhibitor Sensitivity Authors: Yun, C.H. ; Boggon, T.J. ; Li, Y.

  10. Comments of the Southern Environmental Law Center and the American Lung

    Energy Savers [EERE]

    Association in response to the Department of Energy's Emergency Order to Resume Operations at the Potomac River Generating Station in Alexandria, VA | Department of Energy the Southern Environmental Law Center and the American Lung Association in response to the Department of Energy's Emergency Order to Resume Operations at the Potomac River Generating Station in Alexandria, VA Comments of the Southern Environmental Law Center and the American Lung Association in response to the Department

  11. Comparison of direct exposure of human lung cells to modern engine exhaust

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    partricles | Department of Energy direct exposure of human lung cells to modern engine exhaust partricles Comparison of direct exposure of human lung cells to modern engine exhaust partricles 2003 DEER Conference Presentation: Oak Ridge National Laboratory PDF icon 2003_deer_storey.pdf More Documents & Publications Pro-Inflammatory Cytokine Responses to Exposure to Diesel Soot Relationship Between Composition and Toxicity of Engine Emissions Comparative Toxicity of Combined Particle and

  12. Differential metabolism of 4-hydroxynonenal in liver, lung and brain of mice and rats

    SciTech Connect (OSTI)

    Zheng, Ruijin; Dragomir, Ana-Cristina; Mishin, Vladimir; Richardson, Jason R.; Heck, Diane E.; Laskin, Debra L.; Laskin, Jeffrey D.

    2014-08-15

    The lipid peroxidation end-product 4-hydroxynonenal (4-HNE) is generated in tissues during oxidative stress. As a reactive aldehyde, it forms Michael adducts with nucleophiles, a process that disrupts cellular functioning. Liver, lung and brain are highly sensitive to xenobiotic-induced oxidative stress and readily generate 4-HNE. In the present studies, we compared 4-HNE metabolism in these tissues, a process that protects against tissue injury. 4-HNE was degraded slowly in total homogenates and S9 fractions of mouse liver, lung and brain. In liver, but not lung or brain, NAD(P)+ and NAD(P)H markedly stimulated 4-HNE metabolism. Similar results were observed in rat S9 fractions from these tissues. In liver, lung and brain S9 fractions, 4-HNE formed protein adducts. When NADH was used to stimulate 4-HNE metabolism, the formation of protein adducts was suppressed in liver, but not lung or brain. In both mouse and rat tissues, 4-HNE was also metabolized by glutathione S-transferases. The greatest activity was noted in livers of mice and in lungs of rats; relatively low glutathione S-transferase activity was detected in brain. In mouse hepatocytes, 4-HNE was rapidly taken up and metabolized. Simultaneously, 4-HNE-protein adducts were formed, suggesting that 4-HNE metabolism in intact cells does not prevent protein modifications. These data demonstrate that, in contrast to liver, lung and brain have a limited capacity to metabolize 4-HNE. The persistence of 4-HNE in these tissues may increase the likelihood of tissue injury during oxidative stress. - Highlights: • Lipid peroxidation generates 4-hydroxynonenal, a highly reactive aldehyde. • Rodent liver, but not lung or brain, is efficient in degrading 4-hydroxynonenal. • 4-hydroxynonenal persists in tissues with low metabolism, causing tissue damage.

  13. Lung Cancer Survival Prediction using Ensemble Data Mining on Seer Data

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Agrawal, Ankit; Misra, Sanchit; Narayanan, Ramanathan; Polepeddi, Lalith; Choudhary, Alok

    2012-01-01

    We analyze the lung cancer data available from the SEER program with the aim of developing accurate survival prediction models for lung cancer. Carefully designed preprocessing steps resulted in removal/modification/splitting of several attributes, and 2 of the 11 derived attributes were found to have significant predictive power. Several supervised classification methods were used on the preprocessed data along with various data mining optimizations and validations. In our experiments, ensemble voting of five decision tree based classifiers and meta-classifiers was found to result in the best prediction performance in terms of accuracy and area under the ROC curve. We have developedmore » an on-line lung cancer outcome calculator for estimating the risk of mortality after 6 months, 9 months, 1 year, 2 year and 5 years of diagnosis, for which a smaller non-redundant subset of 13 attributes was carefully selected using attribute selection techniques, while trying to retain the predictive power of the original set of attributes. Further, ensemble voting models were also created for predicting conditional survival outcome for lung cancer (estimating risk of mortality after 5 years of diagnosis, given that the patient has already survived for a period of time), and included in the calculator. The on-line lung cancer outcome calculator developed as a result of this study is available at http://info.eecs.northwestern.edu:8080/LungCancerOutcomeCalculator/.« less

  14. Lung Irradiation Increases Mortality After Influenza A Virus Challenge Occurring Late After Exposure

    SciTech Connect (OSTI)

    Manning, Casey M.; Johnston, Carl J.; Department of Pediatrics, University of Rochester Medical Center, Rochester, New York ; Reed, Christina K.; Lawrence, B. Paige; Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York ; Williams, Jacqueline P.; Finkelstein, Jacob N.

    2013-05-01

    Purpose: To address whether irradiation-induced changes in the lung environment alter responses to a viral challenge delivered late after exposure but before the appearance of late lung radiation injury. Methods and Materials: C57BL/6J mice received either lung alone or combined lung and whole-body irradiation (0-15 Gy). At 10 weeks after irradiation, animals were infected with 120 HAU influenza virus strain A/HKx31. Innate and adaptive immune cell recruitment was determined using flow cytometry. Cytokine and chemokine production and protein leakage into the lung after infection were assessed. Results: Prior irradiation led to a dose-dependent failure to regain body weight after infection and exacerbated mortality, but it did not affect virus-specific immune responses or virus clearance. Surviving irradiated animals displayed a persistent increase in total protein in bronchoalveolar lavage fluid and edema. Conclusions: Lung irradiation increased susceptibility to death after infection with influenza virus and impaired the ability to complete recovery. This altered response does not seem to be due to a radiation effect on the immune response, but it may possibly be an effect on epithelial repair.

  15. H. R. 2233: A Bill to amend the Internal Revenue Code of 1986 to increase the gasoline tax for purposes of providing additional revenues for the Mass Transit Account in the Highway Trust Fund and for purposes of reducing the deficit. Introduced in the House of Representatives, One Hundred First Congress, First Session, May 4, 1989

    SciTech Connect (OSTI)

    Not Available

    1989-01-01

    The gasoline tax for the Highway Trust Fund would be increased from 9 cents to 12 cents per gallon, and the deficit reduction rate would be set at 7 cents per gallon. Four cents out of the 12 cent tax for the Highway Trust Fund is designated for mass transit. These increases will not apply to gasohol. The effective date will be the date of enactment.

  16. Examination Report on "The Department of Energy's American Recovery and Reinvestment Act of 2009 Energy Efficiency and Conservation Block Grant Program - Efficiency Maine Trust", OAS-RA-13-04

    Office of Environmental Management (EM)

    The Department of Energy's American Recovery and Reinvestment Act Energy Efficiency and Conservation Block Grant Program - Efficiency Maine Trust OAS-RA-13-04 November 2012 Department of Energy Washington, DC 20585 November 8, 2012 MEMORANDUM FOR THE ASSISTANT SECRETARY FOR ENERGY EFFICIENCY AND RENEWABLE ENERGY FROM: Rickey R. Hass Deputy Inspector General for Audits and Inspections Office of Inspector General SUBJECT: INFORMATION: Examination Report on "The Department of Energy's American

  17. Faith Enterprises Inc. A Service Disabled Veteran-Owned Small Business

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Faith Enterprises Inc. A Service Disabled Veteran-Owned Small Business Security When the Air Force asked Sandia to deliver complex security upgrades to a facility on Kirtland Air Force Base, work began immediately to identify how best to get the job done. Engineers at Sandia teamed with Sandia Contracting Representative Michael Somuk to sub-contract a portion of the work. Because of the sensitive nature of the project, security and previous experience with government contracts were placed as

  18. Dissolution of metal tritides in a simulated lung fluid

    SciTech Connect (OSTI)

    Cheng, Yung-Sung; Dahl, A.R.; Jow, Hong Nian

    1997-10-01

    Metal tritides including titanium tritide (Ti {sup 3}H{sub x}) and erbium tritide (Er {sup 3}H{sub x}) have been used as components of neutron generators. The current understanding of metal tritides and their radiation dosimetry for internal exposure is very limited, and the ICRP Publication 30 does not provide for tritium dosimetry in metal tritide form. However, a few papers in the literature suggest that the solubility of metal tritides could be low. The current radiation protection guidelines for metal tritide particles are based on the assumption that their biological behavior is similar to tritiated water, which could be easily absorbed into body fluid. Therefore, these particles could have relatively short biological half-lives (10 d). If the solubility is low, the biological half-life of metal tritide particles and the dosimetry of an inhalation exposure to these particles could be quite different from tritiated water. This paper describes experiments on the dissolution rate of titanium tritide particles in a simulated lung fluid. Titanium tritide particles with mean sizes of 103 {mu}m (coarse) and 0.95 {mu}m (fine) were used. The results showed that the coarse particles dissolved much more slowly than the fine particles. The long-term dissolution half times were 361 and 33 d for the coarse and fine particles, respectively. Dissolution data of the fine particles were consistent with the diffusion theory. The dissolution half times were longer than the 10-d biological half time for tritiated water in the body. This finding has significant implications for the current health protection guidelines, including annual limits of intakes and derived air concentrations.

  19. Metabolic kinetics and dosimetry of titanium tritide particles in the lung

    SciTech Connect (OSTI)

    Wang, Y.S.; Cheng, Y.S.; Snipes, M.B.; Jow, H.N.

    1996-06-01

    Internal radiation doses resulting from inhaled metal tritide aerosols are potentially a major radiation protection problem encountered by individuals handling tritium. Based on results of experiments with rats intratracheally instilled with titanium tritide particles and on a self-absorption factor of beta energy determined by a numerical method, a biokinetic model was developed for inhaled particles of titanium tritide. Results showed that lung burdens of the tritide are well represented by a 2-component exponential equation; biological half-lives observed for the retention of {sup 3}H in lung were 0.55 d and 64 d, respectively. The tritium clearance rate via urine or feces was described by a sum of three exponential components. At 121 d after instillation, 79.4% of the initial lung burden of {sup 3}H was eliminated of which 34% was excreted by urine, 35.8% via feces, and 9.6 % through exhaled air. After correction for 82% beta energy self-absorption by tritide particles, the cumulative 3H activity in the lungs of rats was 159 kBq d{sup -1} (4.3 {mu}Ci d{sup -1}) per 37 kBq (1 {mu}Ci) of instilled tritide. The cumulative radiation dose to the average lung mass of the rats was 0.28 mGy kBq{sup -1} of instilled tritide. This information will be useful in developing complete metabolic and dosimetric models for inhaled metal tritides for radiation protection purposes.

  20. Inhibitory effect of Disulfiram/copper complex on non-small cell lung cancer cells

    SciTech Connect (OSTI)

    Duan, Lincan; Shen, Hongmei; Zhao, Guangqiang; Yang, Runxiang; Cai, Xinyi; Zhang, Lijuan; Jin, Congguo; Huang, Yunchao

    2014-04-18

    Highlights: Disulfiram and copper synergistically inhibit lung cancer cell proliferation. Lung cancer cell colony formation ability is inhibited by Disulfiram/copper. Disulfiram/copper increases the sensitivity of cisplatin to lung cancer cells. Lung cancer stem cells are specifically targeted by Disulfiram/copper complex. - Abstract: Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related death in both men and women worldwide. Recently, Disulfiram has been reported to be able to inhibit glioblastoma, prostate, or breast cancer cell proliferation. In this study, the synergistic effect of Disulfiram and copper on NSCLC cell growth was investigated. Inhibition of cancer cell proliferation was detected by 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) assay and cell cycle analysis. Liquid colony formation and tumor spheroid formation assays were used to evaluate their effect on cancer cell clonogenicity. Real-time PCR was performed to test the mRNA level of cancer stem cell related genes. We found that Disulfiram or copper alone did not potently inhibit NSCLC cell proliferation in vitro. However, the presence of copper significantly enhanced inhibitory effect of Disulfiram on NSCLC cell growth, indicating a synergistic effect between Disulfiram and copper. Cell cycle analysis showed that Disulfiram/copper complex caused NSCLC cell cycle arrest in G2/M phase. Furthermore, Disulfiram/copper significantly increased the sensitivity of cisplatin in NSCLC cells tested by MTT assay. Liquid colony formation assay revealed that copper dramatically increased the inhibitory effect of Disulfiram on NSCLC cell colony forming ability. Disulfiram combined with copper significantly attenuated NSCLC cell spheroid formation and recuded the mRNA expression of lung cancer stem cell related genes. Our data suggest that Disulfiram/copper complex alone or combined with other chemotherapy is a potential therapeutic strategy for NSCLC patients.

  1. Lung cancer-derived Dickkopf1 is associated with bone metastasis and the mechanism involves the inhibition of osteoblast differentiation

    SciTech Connect (OSTI)

    Chu, Tianqing; Teng, Jiajun; Jiang, Liyan; Zhong, Hua; Han, Baohui

    2014-01-17

    Highlights: DKK1 level was associated with NSCLC bone metastases. Lung tumor cells derived DKK1 inhibited osteoblast differentiation. Lung tumor cells derived DKK1 modulates ?-catenin and RUNX2. -- Abstract: Wnt/?-catenin signaling and Dickkopf1 (DKK1) play important roles in the progression of lung cancer, which preferably metastasizes to skeleton. But the role of them in bone dissemination is poorly understood. This study aims to define the role of DKK1 in lung cancer bone metastases and investigate the underlying mechanism. Our results demonstrated that DKK1 over-expression was a frequent event in non-small-cell lung cancer (NSCLC) blood samples, and serous DKK1 level was much higher in bone metastatic NSCLC compared to non-bone metastatic NSCLC. We also found that conditioned medium from DKK1 over-expressing lung cancer cells inhibited the differentiation of osteoblast, determined by alkaline phosphatase activity and osteocalcin secretion, whereas the conditioned medium from DKK1 silencing lung cancer cells exhibited the opposite effects. Mechanistically, DKK1 reduced the level of ?-catenin and RUNX2, as well as inhibiting the nuclear translocation of ?-catenin. Taken together, these results suggested that lung cancer-produced DKK1 may be an important mechanistic link between NSCLC and bone metastases, and targeting DKK1 may be an effective method to treat bone metastase of NSCLC.

  2. SU-E-CAMPUS-T-02: Can Pre-Treatment 4DCT-Based Motion Margins Estimates Be Trusted for Proton Radiotherapy?

    SciTech Connect (OSTI)

    Seco, J; Koybasi, O; Mishra, P; James, S St.; Lewis, J

    2014-06-15

    Purpose: Radiotherapy motion margins are generated using pre-treatment 4DCT data. The purpose of this study is to assess if pre-treatment 4DCT is sufficient in proton therapy to provide accurate estimate of motion margins. A dosimetric assessment is performed comparing pre-treatment margins with daily-customized margins. Methods: Gold fiducial markers implanted in lung tumors of patients were used to track the tumor. A spherical tumor of diameter 20 mm is inserted into a realistic digital respiratory phantom, where the tumor motion is based on real patient lung tumor trajectories recorded over multiple days. Using Day 1 patient data, 100 ITVs were generated with 1 s interval between consecutive scan start times. Each ITV was made up by the union of 10 tumor positions obtained from 6 s scan time. Two ITV volumes were chosen for treatment planning: ITVmean-? and ITVmean+?. The delivered dose was computed on i) 10 phases forming the planning ITV (10-phase - simulating dose calculation based on 4DCT) and ii) 50 phantoms produced from 100 s of data from any other day with tumor positions sampled every 2 s (dynamic - simulating the dose that would actually be delivered). Results: For similar breathing patterns between Day 1 and any other Day N(>1), the 95% volume coverage (D95) for dynamic case was 8.13% lower than the 10-phase case for ITVmean+?. For breathing patterns that were very different between Day 1 and any other Day N(>1), this difference was as high as 24.5% for ITVmean-?. Conclusion: Proton treatment planning based on pre-treatment 4DCT can lead to under-dosage of the tumor and over-dosage of the surrounding tissues, because of inadequate estimate of the range of motion of the tumor. This is due to the shift of the Bragg peak compared to photon therapy in which the tumor is surrounded by an electron bath.

  3. Predictive Parameters of CyberKnife Fiducial-less (XSight Lung) Applicability for Treatment of Early Non-Small Cell Lung Cancer: A Single-Center Experience

    SciTech Connect (OSTI)

    Bahig, Houda; Campeau, Marie-Pierre; Vu, Toni; Doucet, Robert; Bliveau Nadeau, Dominic; Fortin, Bernard; Roberge, David; Lambert, Louise; Carrier, Jean-Franois; Filion, Edith

    2013-11-01

    Purpose: To determine which parameters allow for CyberKnife fiducial-less tumor tracking in stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer. Methods and Materials: A total of 133 lung SBRT patients were preselected for direct soft-tissue tracking based on manufacturer recommendations (peripherally located tumors ?1.5 cm with a dense appearance) and staff experience. Patients underwent a tumor visualization test to verify adequate detection by the tracking system (orthogonal radiographs). An analysis of potential predictors of successful tumor tracking was conducted looking at: tumor stage, size, histology, tumor projection on the vertebral column or mediastinum, distance to the diaphragm, lung-to-soft tissue ratio, and patient body mass index. Results: Tumor visualization was satisfactory for 88 patients (66%) and unsatisfactory for 45 patients (34%). Median time to treatment start was 6 days in the success group (range, 2-18 days) and 15 days (range, 3-63 days) in the failure group. A stage T2 (P=.04), larger tumor size (volume of 15.3 cm{sup 3} vs 6.5 cm{sup 3} in success and failure group, respectively) (P<.0001), and higher tumor density (0.86 g/cm{sup 3} vs 0.79 g/cm{sup 3}) were predictive of adequate detection. There was a 63% decrease in failure risk with every 1-cm increase in maximum tumor dimension (relative risk for failure = 0.37, CI=0.23-0.60, P=.001). A diameter of 3.6 cm predicted a success probability of 80%. Histology, lung-to-soft tissue ratio, distance to diaphragm, patient's body mass index, and tumor projection on vertebral column and mediastinum were not found to be predictive of success. Conclusions: Tumor size, volume, and density were the most predictive factors of a successful XSight Lung tumor tracking. Tumors >3.5 cm have ?80% chance of being adequately visualized and therefore should all be considered for direct tumor tracking.

  4. Cell-specific oxidative stress and cytotoxicity after wildfire coarse particulate matter instillation into mouse lung

    SciTech Connect (OSTI)

    Williams, Keisha M.; Franzi, Lisa M.; Last, Jerold A.

    2013-01-01

    Our previous work has shown that coarse particulate matter (PM{sub 10-2.5}) from wildfire smoke is more toxic to lung macrophages on an equal dose (by mass) basis than coarse PM isolated from normal ambient air, as evidenced by decreased numbers of macrophages in lung lavage fluid 6 and 24 hours after PM instillation into mouse lungs in vivo and by cytotoxicity to a macrophage cell line observed directly in vitro. We hypothesized that pulmonary macrophages from mice instilled with wildfire coarse PM would undergo more cytotoxicity than macrophages from controls, and that there would be an increase in oxidative stress in their lungs. Cytotoxicity was quantified as decreased viable macrophages and increased percentages of dead macrophages in the bronchoalveolar lavage fluid (BALF) of mice instilled with wildfire coarse PM. At 1 hour after PM instillation, we observed both decreased numbers of viable macrophages and increased dead macrophage percentages as compared to controls. An increase in free isoprostanes, an indicator of oxidative stress, from control values of 28.1 3.2 pg/mL to 83.9 12.2 pg/mL was observed a half-hour after PM instillation. By 1 hour after PM instillation, isoprostane values had returned to 30.4 7.6 pg/mL, not significantly different from control concentrations. Lung sections from mice instilled with wildfire coarse PM showed rapid Clara cell responses, with decreased intracellular staining for the Clara cell secretory protein CCSP 1 hour after wildfire PM instillation. In conclusion, very rapid cytotoxicity occurs in pulmonary macrophages and oxidative stress responses are seen 0.51 hour after wildfire coarse PM instillation. These results define early cellular and biochemical events occurring in vivo and support the hypothesis that oxidative stress-mediated macrophage toxicity plays a key role in the initial response of the mouse lung to wildfire PM exposure. -- Highlights: ? We studied very early events (0.51 hour) after giving wildfire PM{sub 10-2.5} to mice. ? Wildfire PM{sub 10-2.5} rapidly kills lung macrophages in mice. ? Wildfire PM{sub 10-2.5} rapidly elicits oxidative stress in mice. ? Wildfire PM{sub 10-2.5} rapidly elicits Clara cell CCSP secretion in mice. ? Wildfire PM{sub 10-2.5} rapidly elicits TNF-? secretion into BALF in mice.

  5. Inhibition of chlorine-induced lung injury by the type 4 phosphodiesterase inhibitor rolipram

    SciTech Connect (OSTI)

    Chang, Weiyuan; Chen, Jing; Schlueter, Connie F.; Rando, Roy J.; Pathak, Yashwant V.; Hoyle, Gary W.

    2012-09-01

    Chlorine is a highly toxic respiratory irritant that when inhaled causes epithelial cell injury, alveolar-capillary barrier disruption, airway hyperreactivity, inflammation, and pulmonary edema. Chlorine is considered a chemical threat agent, and its release through accidental or intentional means has the potential to result in mass casualties from acute lung injury. The type 4 phosphodiesterase inhibitor rolipram was investigated as a rescue treatment for chlorine-induced lung injury. Rolipram inhibits degradation of the intracellular signaling molecule cyclic AMP. Potential beneficial effects of increased cyclic AMP levels include inhibition of pulmonary edema, inflammation, and airway hyperreactivity. Mice were exposed to chlorine (whole body exposure, 228270 ppm for 1 h) and were treated with rolipram by intraperitoneal, intranasal, or intramuscular (either aqueous or nanoemulsion formulation) delivery starting 1 h after exposure. Rolipram administered intraperitoneally or intranasally inhibited chlorine-induced pulmonary edema. Minor or no effects were observed on lavage fluid IgM (indicative of plasma protein leakage), KC (Cxcl1, neutrophil chemoattractant), and neutrophils. All routes of administration inhibited chlorine-induced airway hyperreactivity assessed 1 day after exposure. The results of the study suggest that rolipram may be an effective rescue treatment for chlorine-induced lung injury and that both systemic and targeted administration to the respiratory tract were effective routes of delivery. -- Highlights: ? Chlorine causes lung injury when inhaled and is considered a chemical threat agent. ? Rolipram inhibited chlorine-induced pulmonary edema and airway hyperreactivity. ? Post-exposure rolipram treatments by both systemic and local delivery were effective. ? Rolipram shows promise as a rescue treatment for chlorine-induced lung injury.

  6. Diet-induced obesity reprograms the inflammatory response of the murine lung to inhaled endotoxin

    SciTech Connect (OSTI)

    Tilton, Susan C.; Waters, Katrina M.; Karin, Norman J.; Webb-Robertson, Bobbie-Jo M.; Zangar, Richard C.; Lee, K. Monica; Bigelow, Diana J.; Pounds, Joel G.; Corley, Richard A.

    2013-03-01

    The co-occurrence of environmental factors is common in complex human diseases and, as such, understanding the molecular responses involved is essential to determine risk and susceptibility to disease. We have investigated the key biological pathways that define susceptibility for pulmonary infection during obesity in diet-induced obese (DIO) and regular weight (RW) C57BL/6 mice exposed to inhaled lipopolysaccharide (LPS). LPS induced a strong inflammatory response in all mice as indicated by elevated cell counts of macrophages and neutrophils and levels of proinflammatory cytokines (MDC, MIP-1?, IL-12, RANTES) in the bronchoalveolar lavage fluid. Additionally, DIO mice exhibited 50% greater macrophage cell counts, but decreased levels of the cytokines, IL-6, TARC, TNF-?, and VEGF relative to RW mice. Microarray analysis of lung tissue showed over half of the LPS-induced expression in DIO mice consisted of genes unique for obese mice, suggesting that obesity reprograms how the lung responds to subsequent insult. In particular, we found that obese animals exposed to LPS have gene signatures showing increased inflammatory and oxidative stress response and decreased antioxidant capacity compared with RW. Because signaling pathways for these responses can be common to various sources of environmentally induced lung damage, we further identified biomarkers that are indicative of specific toxicant exposure by comparing gene signatures after LPS exposure to those from a parallel study with cigarette smoke. These data show obesity may increase sensitivity to further insult and that co-occurrence of environmental stressors result in complex biosignatures that are not predicted from analysis of individual exposures. - Highlights: ? Obesity modulates inflammatory markers in BAL fluid after LPS exposure. ? Obese animals have a unique transcriptional signature in lung after LPS exposure. ? Obesity elevates inflammatory stress and reduces antioxidant capacity in the lung. ? Toxicant-specific biomarkers predict exposure independent of systemic inflammation.

  7. Real-time soft tissue motion estimation for lung tumors during radiotherapy delivery

    SciTech Connect (OSTI)

    Rottmann, Joerg; Berbeco, Ross; Keall, Paul

    2013-09-15

    Purpose: To provide real-time lung tumor motion estimation during radiotherapy treatment delivery without the need for implanted fiducial markers or additional imaging dose to the patient.Methods: 2D radiographs from the therapy beam's-eye-view (BEV) perspective are captured at a frame rate of 12.8 Hz with a frame grabber allowing direct RAM access to the image buffer. An in-house developed real-time soft tissue localization algorithm is utilized to calculate soft tissue displacement from these images in real-time. The system is tested with a Varian TX linear accelerator and an AS-1000 amorphous silicon electronic portal imaging device operating at a resolution of 512 × 384 pixels. The accuracy of the motion estimation is verified with a dynamic motion phantom. Clinical accuracy was tested on lung SBRT images acquired at 2 fps.Results: Real-time lung tumor motion estimation from BEV images without fiducial markers is successfully demonstrated. For the phantom study, a mean tracking error <1.0 mm [root mean square (rms) error of 0.3 mm] was observed. The tracking rms accuracy on BEV images from a lung SBRT patient (≈20 mm tumor motion range) is 1.0 mm.Conclusions: The authors demonstrate for the first time real-time markerless lung tumor motion estimation from BEV images alone. The described system can operate at a frame rate of 12.8 Hz and does not require prior knowledge to establish traceable landmarks for tracking on the fly. The authors show that the geometric accuracy is similar to (or better than) previously published markerless algorithms not operating in real-time.

  8. Renewable Energy Resources Trust Fund

    Broader source: Energy.gov [DOE]

    Renewable-energy projects eligible for RERTF support include wind energy, solar-thermal energy, photovoltaics, dedicated crops grown for energy production and organic waste biomass, hydropower th...

  9. Metabolite signatures in hydrophilic extracts of mouse lungs exposed to cigarette smoke revealed by 1H NMR metabolomics investigation

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Hu, Jian Z.; Wang, Xuan; Feng, Ju; Webb-Robertson, Bobbie-Jo M.; Waters, Katrina M.; Tilton, Susan C.; Pounds, Joel G.; Corley, Richard A.; Liu, Maili; Hu, Mary Y.

    2015-05-12

    Herein, 1H-NMR metabolomics are carried out to evaluate the changes of metabolites in lungs of mice exposed to cigarette smoke. It is found that the concentrations of adenosine derivatives (i.e. ATP, ADP and AMP), inosine and uridine are significantly fluctuated in the lungs of mice exposed to cigarette smoke compared with those of controls regardless the mouse is obese or regular weight. The decreased ATP, ADP, AMP and elevated inosine predict that the deaminases in charge of adenosine derivatives to inosine derivatives conversion are altered in lungs of mice exposed to cigarette smoke. Transcriptional analysis reveals that the concentrations ofmore » adenosine monophosphate deaminase and adenosine deaminase are different in the lungs of mice exposed to cigarette smoke, confirming the prediction from metabolomics studies. We also found, for the first time, that the ratio of glycerophosphocholine (GPC) to phosphocholine (PC) is significantly increased in the lungs of obese mice compared with regular weight mice. The ratio of GPC/PC is further elevated in the lungs of obese group by cigarette smoke exposure. Since GPC/PC ratio is a known biomarker for cancer, these results may suggest that obese group is more susceptible to lung cancer when exposed to cigarette smoke.« less

  10. Impact of Four-Dimensional Computed Tomography Pulmonary Ventilation Imaging-Based Functional Avoidance for Lung Cancer Radiotherapy

    SciTech Connect (OSTI)

    Yamamoto, Tokihiro; Kabus, Sven; Berg, Jens von; Lorenz, Cristian; Keall, Paul J.

    2011-01-01

    Purpose: To quantify the dosimetric impact of four-dimensional computed tomography (4D-CT) pulmonary ventilation imaging-based functional treatment planning that avoids high-functional lung regions. Methods and Materials: 4D-CT ventilation images were created from 15 non-small-cell lung cancer patients using deformable image registration and quantitative analysis of the resultant displacement vector field. For each patient, anatomic and functional plans were created for intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT). Consistent beam angles and dose-volume constraints were used for all cases. The plans with Radiation Therapy Oncology Group (RTOG) 0617-defined major deviations were modified until clinically acceptable. Functional planning spared the high-functional lung, and anatomic planning treated the lungs as uniformly functional. We quantified the impact of functional planning compared with anatomic planning using the two- or one-tailed t test. Results: Functional planning led to significant reductions in the high-functional lung dose, without significantly increasing other critical organ doses, but at the expense of significantly degraded the planning target volume (PTV) conformity and homogeneity. The average reduction in the high-functional lung mean dose was 1.8 Gy for IMRT (p < .001) and 2.0 Gy for VMAT (p < .001). Significantly larger changes occurred in the metrics for patients with a larger amount of high-functional lung adjacent to the PTV. Conclusion: The results of the present study have demonstrated the impact of 4D-CT ventilation imaging-based functional planning for IMRT and VMAT for the first time. Our findings indicate the potential of functional planning in lung functional avoidance for both IMRT and VMAT, particularly for patients who have high-functional lung adjacent to the PTV.

  11. H. R. 3467: a Bill to amend the Internal Revenue Code of 1954 to impose a surcharge tax on business activities to provide revenues for the trust fund known as the Hazardous Substance Response Superfund. Introduced in the House of Representatives, Ninety-Ninth Congress, First Session, October 1, 1985

    SciTech Connect (OSTI)

    Not Available

    1985-01-01

    The Superfund Revenue Act of 1985 (H.R. 3467) amends the Internal Revenue Code of 1954 and provides income for the Superfund trust fund by imposing a surcharge tax on business activities designated in section 4002 and varying with the number of employees. The bill also defines activities according to category of business and the degree of direct and indirect labor. Later sections describe the tax period and procedures for tax payments, exemptions for government entities and charitable organizations, neutrality for import and export goods, and other limitations and requirements involving payments to the trust fund.

  12. Arsenic methylation and lung and bladder cancer in a case-control study in northern Chile

    SciTech Connect (OSTI)

    Melak, Dawit; Ferreccio, Catterina; Kalman, David; Parra, Roxana; Acevedo, Johanna; Prez, Liliana; Corts, Sandra; Smith, Allan H.; Yuan, Yan; Liaw, Jane; Steinmaus, Craig

    2014-01-15

    In humans, ingested inorganic arsenic is metabolized to monomethylarsenic (MMA) then to dimethylarsenic (DMA), although this process is not complete in most people. The trivalent form of MMA is highly toxic in vitro and previous studies have identified associations between the proportion of urinary arsenic as MMA (%MMA) and several arsenic-related diseases. To date, however, relatively little is known about its role in lung cancer, the most common cause of arsenic-related death, or about its impacts on people drinking water with lower arsenic concentrations (e.g., < 200 ?g/L). In this study, urinary arsenic metabolites were measured in 94 lung and 117 bladder cancer cases and 347 population-based controls from areas in northern Chile with a wide range of drinking water arsenic concentrations. Lung cancer odds ratios adjusted for age, sex, and smoking by increasing tertiles of %MMA were 1.00, 1.91 (95% confidence interval (CI), 0.993.67), and 3.26 (1.766.04) (p-trend < 0.001). Corresponding odds ratios for bladder cancer were 1.00, 1.81 (1.063.11), and 2.02 (1.153.54) (p-trend < 0.001). In analyses confined to subjects only with arsenic water concentrations < 200 ?g/L (median = 60 ?g/L), lung and bladder cancer odds ratios for subjects in the upper tertile of %MMA compared to subjects in the lower two tertiles were 2.48 (1.085.68) and 2.37 (1.015.57), respectively. Overall, these findings provide evidence that inter-individual differences in arsenic metabolism may be an important risk factor for arsenic-related lung cancer, and may play a role in cancer risks among people exposed to relatively low arsenic water concentrations. - Highlights: Urine arsenic metabolites were measured in cancer cases and controls from Chile. Higher urine %MMA values were associated with increased lung and bladder cancer. %MMA-cancer associations were seen at drinking water arsenic levels < 200 ?g/L.

  13. SU-E-J-149: Establishing the Relationship Between Pre-Treatment Lung Ventilation, Dose, and Toxicity Outcome

    SciTech Connect (OSTI)

    Mistry, N; D'Souza, W; Sornsen de Koste, J; Senan, S

    2014-06-01

    Purpose: Recently, there has been an interest in incorporating functional information in treatment planning especially in thoracic tumors. The rationale is that healthy lung regions need to be spared from radiation if possible to help achieve better control on toxicity. However, it is still unclear whether high functioning regions need to be spared or have more capacity to deal with the excessive radiation as compared to the compromised regions of the lung. Our goal with this work is to establish the tools by which we can establish a relationship between pre-treatment lung function, dose, and radiographic outcomes of lung toxicity. Methods: Treatment planning was performed using a single phase of a 4DCT scan, and follow-up anatomical CT scans were performed every 3 months for most patients. In this study, we developed the pipeline of tools needed to analyze such a large dataset, while trying to establish a relationship between function, dose, and outcome. Pre-treatment lung function was evaluated using a recently published technique that evaluates Fractional Regional Ventilation (FRV). All images including the FRV map and the individual follow-up anatomical CT images were all spatially matched to the planning CT using a diffusion based Demons image registration algorithm. Change in HU value was used as a metric to capture the effects of lung toxicity. To validate the findings, a radiologist evaluated the follow-up anatomical CT images and scored lung toxicity. Results: Initial experience in 1 patient shows a relationship between the pre-treatment lung function, dose and toxicity outcome. The results are also correlated to the findings by the radiologist who was blinded to the analysis or dose. Conclusion: The pipeline we have established to study this enables future studies in large retrospective studies. However, the tools are dependent on the fidelity of 4DCT reconstruction for accurate evaluation of regional ventilation. Patent Pending for the technique presented in this work to evaluate FRV incorporating mass correction.

  14. Attenuation of acute nitrogen mustard-induced lung injury, inflammation and fibrogenesis by a nitric oxide synthase inhibitor

    SciTech Connect (OSTI)

    Malaviya, Rama; Venosa, Alessandro; Hall, LeRoy; Gow, Andrew J.; Sinko, Patrick J.; Laskin, Jeffrey D.; Laskin, Debra L.

    2012-12-15

    Nitrogen mustard (NM) is a toxic vesicant known to cause damage to the respiratory tract. Injury is associated with increased expression of inducible nitric oxide synthase (iNOS). In these studies we analyzed the effects of transient inhibition of iNOS using aminoguanidine (AG) on NM-induced pulmonary toxicity. Rats were treated intratracheally with 0.125 mg/kg NM or control. Bronchoalveolar lavage fluid (BAL) and lung tissue were collected 1 d28 d later and lung injury, oxidative stress and fibrosis assessed. NM exposure resulted in progressive histopathological changes in the lung including multifocal lesions, perivascular and peribronchial edema, inflammatory cell accumulation, alveolar fibrin deposition, bronchiolization of alveolar septal walls, and fibrosis. This was correlated with trichrome staining and expression of proliferating cell nuclear antigen (PCNA). Expression of heme oxygenase (HO)-1 and manganese superoxide dismutase (Mn-SOD) was also increased in the lung following NM exposure, along with levels of protein and inflammatory cells in BAL, consistent with oxidative stress and alveolar-epithelial injury. Both classically activated proinflammatory (iNOS{sup +} and cyclooxygenase-2{sup +}) and alternatively activated profibrotic (YM-1{sup +} and galectin-3{sup +}) macrophages appeared in the lung following NM administration; this was evident within 1 d, and persisted for 28 d. AG administration (50 mg/kg, 2 /day, 1 d3 d) abrogated NM-induced injury, oxidative stress and inflammation at 1 d and 3 d post exposure, with no effects at 7 d or 28 d. These findings indicate that nitric oxide generated via iNOS contributes to acute NM-induced lung toxicity, however, transient inhibition of iNOS is not sufficient to protect against pulmonary fibrosis. -- Highlights: ? Nitrogen mustard (NM) induces acute lung injury and fibrosis. ? Pulmonary toxicity is associated with increased expression of iNOS. ? Transient inhibition of iNOS attenuates acute lung injury induced by NM.

  15. Analysis of lung tumor initiation and progression in transgenic mice for Cre-inducible overexpression of Cul4A gene

    SciTech Connect (OSTI)

    Wang, Yang; Xu, Zhidong; Mao, Jian -Hua; Hung, Ming -Szu; Hsieh, David; Au, Alfred; Jablons, David M.; You, Liang

    2015-06-08

    Background: Lung cancer is the leading cause of morbidity and death worldwide. Although the available lung cancer animal models have been informative and further propel our understanding of human lung cancer, they still do not fully recapitulate the complexities of human lung cancer. The pathogenesis of lung cancer remains highly elusive because of its aggressive biologic nature and considerable heterogeneity, compared to other cancers. The association of Cul4A amplification with aggressive tumor growth and poor prognosis has been suggested. Our previous study suggested that Cul4A is oncogenic in vitro, but its oncogenic role in vivo has not been studied. Methods: Viral delivery approaches have been used extensively to model cancer in mouse models. In our experiments, we used Cre-recombinase induced overexpression of the Cul4A gene in transgenic mice to study the role of Cul4A on lung tumor initiation and progression and have developed a new model of lung tumor development in mice harboring a conditionally expressed allele of Cul4A. Results: Here we show that the use of a recombinant adenovirus expressing Cre-recombinase (AdenoCre) to induce Cul4A overexpression in the lungs of mice allows controls of the timing and multiplicity of tumor initiation. Following our mouse models, we are able to study the potential role of Cul4A in the development and progression in pulmonary adenocarcinoma as well. Conclusion: Our findings indicate that Cul4A is oncogenic in vivo, and this mouse model is a tool in understanding the mechanisms of Cul4A in human cancers and for testing experimental therapies targeting Cul4A.

  16. Analysis of lung tumor initiation and progression in transgenic mice for Cre-inducible overexpression of Cul4A gene

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Wang, Yang; Xu, Zhidong; Mao, Jian -Hua; Hung, Ming -Szu; Hsieh, David; Au, Alfred; Jablons, David M.; You, Liang

    2015-06-08

    Background: Lung cancer is the leading cause of morbidity and death worldwide. Although the available lung cancer animal models have been informative and further propel our understanding of human lung cancer, they still do not fully recapitulate the complexities of human lung cancer. The pathogenesis of lung cancer remains highly elusive because of its aggressive biologic nature and considerable heterogeneity, compared to other cancers. The association of Cul4A amplification with aggressive tumor growth and poor prognosis has been suggested. Our previous study suggested that Cul4A is oncogenic in vitro, but its oncogenic role in vivo has not been studied. Methods:more » Viral delivery approaches have been used extensively to model cancer in mouse models. In our experiments, we used Cre-recombinase induced overexpression of the Cul4A gene in transgenic mice to study the role of Cul4A on lung tumor initiation and progression and have developed a new model of lung tumor development in mice harboring a conditionally expressed allele of Cul4A. Results: Here we show that the use of a recombinant adenovirus expressing Cre-recombinase (“AdenoCre”) to induce Cul4A overexpression in the lungs of mice allows controls of the timing and multiplicity of tumor initiation. Following our mouse models, we are able to study the potential role of Cul4A in the development and progression in pulmonary adenocarcinoma as well. Conclusion: Our findings indicate that Cul4A is oncogenic in vivo, and this mouse model is a tool in understanding the mechanisms of Cul4A in human cancers and for testing experimental therapies targeting Cul4A.« less

  17. Residential Mobility and Lung Cancer Risk: Data-Driven Exploration Using Internet Sources

    SciTech Connect (OSTI)

    Yoon, Hong-Jun; Tourassi, Georgia; Xu, Songhua

    2015-01-01

    Frequent relocation has been linked to health decline, particularly with respect to emotional and psychological wellbeing. In this paper we investigate whether there is an association between frequent relocation and lung cancer risk. For the initial investigation we leverage two online data sources to collect cancer and control subjects using web crawling and tailored text mining. The two data sources share different strengths and weaknesses in terms of the amount of detail, population representation, and sample size. One data source includes online obituaries. The second data source includes augmented LinkedIn profiles. For each data source, the subjects spatiotemporal history is reconstructed from the available information provided in the obituaries and from the education and work experience provided in the LinkedIn profiles. The study shows that lung cancer subjects have higher mobility frequency than the control group. This trend is consistent for both data sources.

  18. Optimization of leaf margins for lung stereotactic body radiotherapy using a flattening filter-free beam

    SciTech Connect (OSTI)

    Wakai, Nobuhide; Sumida, Iori; Otani, Yuki; Suzuki, Osamu; Seo, Yuji; Isohashi, Fumiaki; Yoshioka, Yasuo; Ogawa, Kazuhiko; Hasegawa, Masatoshi

    2015-05-15

    Purpose: The authors sought to determine the optimal collimator leaf margins which minimize normal tissue dose while achieving high conformity and to evaluate differences between the use of a flattening filter-free (FFF) beam and a flattening-filtered (FF) beam. Methods: Sixteen lung cancer patients scheduled for stereotactic body radiotherapy underwent treatment planning for a 7 MV FFF and a 6 MV FF beams to the planning target volume (PTV) with a range of leaf margins (?3 to 3 mm). Forty grays per four fractions were prescribed as a PTV D95. For PTV, the heterogeneity index (HI), conformity index, modified gradient index (GI), defined as the 50% isodose volume divided by target volume, maximum dose (Dmax), and mean dose (Dmean) were calculated. Mean lung dose (MLD), V20 Gy, and V5 Gy for the lung (defined as the volumes of lung receiving at least 20 and 5 Gy), mean heart dose, and Dmax to the spinal cord were measured as doses to organs at risk (OARs). Paired t-tests were used for statistical analysis. Results: HI was inversely related to changes in leaf margin. Conformity index and modified GI initially decreased as leaf margin width increased. After reaching a minimum, the two values then increased as leaf margin increased (V shape). The optimal leaf margins for conformity index and modified GI were ?1.1 0.3 mm (mean 1 SD) and ?0.2 0.9 mm, respectively, for 7 MV FFF compared to ?1.0 0.4 and ?0.3 0.9 mm, respectively, for 6 MV FF. Dmax and Dmean for 7 MV FFF were higher than those for 6 MV FF by 3.6% and 1.7%, respectively. There was a positive correlation between the ratios of HI, Dmax, and Dmean for 7 MV FFF to those for 6 MV FF and PTV size (R = 0.767, 0.809, and 0.643, respectively). The differences in MLD, V20 Gy, and V5 Gy for lung between FFF and FF beams were negligible. The optimal leaf margins for MLD, V20 Gy, and V5 Gy for lung were ?0.9 0.6, ?1.1 0.8, and ?2.1 1.2 mm, respectively, for 7 MV FFF compared to ?0.9 0.6, ?1.1 0.8, and ?2.2 1.3 mm, respectively, for 6 MV FF. With the heart inside the radiation field, the mean heart dose showed a V-shaped relationship with leaf margins. The optimal leaf margins were ?1.0 0.6 mm for both beams. Dmax to the spinal cord showed no clear trend for changes in leaf margin. Conclusions: The differences in doses to OARs between FFF and FF beams were negligible. Conformity index, modified GI, MLD, lung V20 Gy, lung V5 Gy, and mean heart dose showed a V-shaped relationship with leaf margins. There were no significant differences in optimal leaf margins to minimize these parameters between both FFF and FF beams. The authors results suggest that a leaf margin of ?1 mm achieves high conformity and minimizes doses to OARs for both FFF and FF beams.

  19. Effects of effluents of coal combustion and gasification upon lung structure and function. Annual report

    SciTech Connect (OSTI)

    Hinton, D.E.

    1980-01-01

    The overall objective of the proposed research is to correlate both structural and functional alterations in cells and tissues of the lung brought about by exposure to fluidized bed combustion and fixed bed gasification effluents and reagent grade oxides of metals known to be associated with coal combustion gasification. Projected milestones are described. Progress during the first year in setting up aerosol exposure facilities, intratracheal instillations, pulmonary mechanics, and morphometric examinations is reported. (DMC)

  20. Classical and alternative macrophage activation in the lung following ozone-induced oxidative stress

    SciTech Connect (OSTI)

    Sunil, Vasanthi R.; Patel-Vayas, Kinal; Shen, Jianliang; Laskin, Jeffrey D.; Laskin, Debra L.

    2012-09-01

    Ozone is a pulmonary irritant known to cause oxidative stress, inflammation and tissue injury. Evidence suggests that macrophages play a role in the pathogenic response; however, their contribution depends on the mediators they encounter in the lung which dictate their function. In these studies we analyzed the effects of ozone-induced oxidative stress on the phenotype of alveolar macrophages (AM). Exposure of rats to ozone (2 ppm, 3 h) resulted in increased expression of 8-hydroxy-2?-deoxyguanosine (8-OHdG), as well as heme oxygenase-1 (HO-1) in AM. Whereas 8-OHdG was maximum at 24 h, expression of HO-1 was biphasic increasing after 3 h and 4872 h. Cleaved caspase-9 and beclin-1, markers of apoptosis and autophagy, were also induced in AM 24 h post-ozone. This was associated with increased bronchoalveolar lavage protein and cells, as well as matrix metalloproteinase (MMP)-2 and MMP-9, demonstrating alveolar epithelial injury. Ozone intoxication resulted in biphasic activation of the transcription factor, NF?B. This correlated with expression of monocyte chemotactic protein?1, inducible nitric oxide synthase and cyclooxygenase?2, markers of proinflammatory macrophages. Increases in arginase-1, Ym1 and galectin-3 positive anti-inflammatory/wound repair macrophages were also observed in the lung after ozone inhalation, beginning at 24 h (arginase-1, Ym1), and persisting for 72 h (galectin-3). This was associated with increased expression of pro-surfactant protein-C, a marker of Type II cell proliferation and activation, important steps in wound repair. These data suggest that both proinflammatory/cytotoxic and anti-inflammatory/wound repair macrophages are activated early in the response to ozone-induced oxidative stress and tissue injury. -- Highlights: ? Lung macrophages are highly sensitive to ozone induced oxidative stress. ? Ozone induces autophagy and apoptosis in lung macrophages. ? Proinflammatory and wound repair macrophages are activated early after ozone. ? Oxidative stress may contribute to regulating macrophage phenotype and function.

  1. Appraisal of selected epidemiologic issues from studies of lung cancer among uranium and hard rock miners

    SciTech Connect (OSTI)

    Petersen, G R; Sever, L E

    1982-04-01

    An extensive body of published information about lung cancer among uranium miners was reviewed and diverse information, useful in identifying important issues but not in resolving them was found. Measuring exposure and response; thresholds of exposure; latency or the period from first mining experience to death; effort to predict excess risk of death, using a model; effects of smoking and radon daughter exposure on the histology of lung tumors; and the interplay of factors on the overall risk of death were all examined. The general concept of thresholds; that is, an exposure level below which risk does not increase was considered. The conclusion is that it should be possible to detect and estimate an epidemiologic threshold when the cohorts have been followed to the death of all members. Issues concerning latency in the studies of uranium miners published to date were examined. It is believed that the induction-latent period for lung cancer among uranium miners may be: as little as 10 to more than 40 years; dependent on age at which exposure begins; exposure rate; and ethnicity or smoking habits. Although suggested as factual, their existence is uncertain. An effect due to the exposure rate may exist although it has not been factual, their existence is uncertain. An effect due to the exposure rate may exist although it has not been confirmed. The median induction-latent period appears to be in excess of the 15 years frequently cited for US uranium miner. A distinct pattern of shorter induction-latent periods with increasing age at first mining exposure is reported. The evidence for and against an unusual histologic pattern of lung cancers among uranium miners was examined. The ratio of epidermoid to small cell types was close to 1:2; the ratio in the general population is nearer 2:1. The histologic pattern warrants closer attention of pathologists and epidemiologists. (ERB) (ERB)

  2. Predicting the Risk of Secondary Lung Malignancies Associated With Whole-Breast Radiation Therapy

    SciTech Connect (OSTI)

    Ng, John; Shuryak, Igor; Xu Yanguang; Clifford Chao, K.S.; Brenner, David J.; Burri, Ryan J.

    2012-07-15

    Purpose: The risk of secondary lung malignancy (SLM) is a significant concern for women treated with whole-breast radiation therapy after breast-conserving surgery for early-stage breast cancer. In this study, a biologically based secondary malignancy model was used to quantify the risk of secondary lung malignancies (SLMs) associated with several common methods of delivering whole-breast radiation therapy (RT). Methods and Materials: Both supine and prone computed tomography simulations of 15 women with early breast cancer were used to generate standard fractionated and hypofractionated whole-breast RT treatment plans for each patient. Dose-volume histograms (DVHs) of the ipsilateral breast and lung were calculated for each patient on each plan. A model of spontaneous and radiation-induced carcinogenesis was used to determine the relative risks of SLMs for the different treatment techniques. Results: A higher risk of SLMs was predicted for supine breast irradiation when compared with prone breast irradiation for both the standard fractionation and hypofractionation schedules (relative risk [RR] = 2.59, 95% confidence interval (CI) = 2.30-2.88, and RR = 2.68, 95% CI = 2.39-2.98, respectively). No difference in risk of SLMs was noted between standard fractionation and hypofractionation schedules in either the supine position (RR = 1.05, 95% CI = 0.97-1.14) or the prone position (RR = 1.01, 95% CI = 0.88-1.15). Conclusions: Compared with supine whole-breast irradiation, prone breast irradiation is associated with a significantly lower predicted risk of secondary lung malignancy. In this modeling study, fractionation schedule did not have an impact on the risk of SLMs in women treated with whole-breast RT for early breast cancer.

  3. In Vivo Evaluation of Lung Microwave Ablation in a Porcine Tumor Mimic Model

    SciTech Connect (OSTI)

    Planche, Olivier; Teriitehau, Christophe; Boudabous, Sana; Robinson, Joey Marie; Rao, Pramod; Deschamps, Frederic; Farouil, Geoffroy; Baere, Thierry de

    2013-02-15

    To evaluate the microwave ablation of created tumor mimics in the lung of a large animal model (pigs), with examination of the ablative synergy of multiple antennas. Fifty-six tumor-mimic models of various sizes were created in 15 pigs by using barium-enriched minced collected thigh muscle injected into the lung of the same animal. Tumors were ablated under fluoroscopic guidance by single-antenna and multiple-antenna microwaves. Thirty-five tumor models were treated in 11 pigs with a single antenna at 75 W for 15 min, with 15 measuring 20 mm in diameter, 10 measuring 30 mm, and 10 measuring 40 mm. Mean circularity of the single-antenna ablation zones measured 0.64 {+-} 0.12, with a diameter of 35.7 {+-} 8.7 mm along the axis of the antenna and 32.7 {+-} 12.8 mm perpendicular to the feeding point. Multiple-antenna delivery of 75 W for 15 min caused intraprocedural death of 2 animals; modified protocol to 60 W for 10 min resulted in an ablation zone with a diameter of 43.0 {+-} 7.7 along the axis of the antenna and 54.8 {+-} 8.5 mm perpendicular to the feeding point; circularity was 0.70 {+-} 0.10. A single microwave antenna can create ablation zones large enough to cover lung tumor mimic models of {<=}4 cm with no heat sink effect from vessels of {<=}6 mm. Synergic use of 3 antennas allows ablation of larger volumes than single-antenna or radiofrequency ablation, but great caution must be taken when 3 antennas are used simultaneously in the lung in clinical practice.

  4. The respiratory health and lung function of Anglo-American children in a smelter town

    SciTech Connect (OSTI)

    Dodge, R.

    1983-02-01

    Cooper smelters are large, usually isolated, sources of air pollution. Arizona has several such plants on the periphery of small communities. The smelters emit predominantly sulfur oxides and particulates, and the residents of these communities intermittently are exposed to high concentrations (24-h sulfur dioxide (SO2) . 250 to 500 micrograms/m3) of smelter smoke but little other pollution. This study compared the respiratory health of Anglo-American school children who lived in one smelter community with children living in another small community in Arizona that was free of smelter air pollution. The prevalence of cough, as determined by questionnaire, was 25.6% in the smelter town children and 14.3% in the nonsmelter town children (p less than 0.05). Pulmonary function at the study onset was equal in the two groups. Over the course of the 4 yr of study, lung function growth (measured as actual forced expiratory volume in one second (FEV1) after 4 yr of study minus predicted FEV1) was also equal in the smelter town and nonsmelter town children. These results suggest that children in smelter communities have slightly more cough when compared with children living in other communities, but no differences in initial lung function or lung function at yearly testing over the period of the study.

  5. High-Resolution Phase-Contrast Imaging of Submicron Particles in Unstained Lung Tissue

    SciTech Connect (OSTI)

    Schittny, J. C.; Barre, S. F.; Haberthuer, D.; Mokso, R.; Tsuda, A.; Stampanoni, M.

    2011-09-09

    To access the risks and chances of deposition of submicron particles in the gas-exchange area of the lung, a precise three-dimensional (3D)-localization of the sites of deposition is essential--especially because local peaks of deposition are expected in the acinar tree and in individual alveoli. In this study we developed the workflow for such an investigation. We administered 200-nm gold particles to young adult rats by intratracheal instillation. After fixation and paraffin embedding, their lungs were imaged unstained using synchrotron radiation x-ray tomographic microscopy (SRXTM) at the beamline TOMCAT (Swiss Light Source, Villigen, Switzerland) at sample detector distances of 2.5 mm (absorption contrast) and of 52.5 mm (phase contrast). A segmentation based on a global threshold of grey levels was successfully done on absorption-contrast images for the gold and on the phase-contrast images for the tissue. The smallest spots containing gold possessed a size of 1-2 voxels of 370-nm side length. We conclude that a combination of phase and absorption contrast SRXTM imaging is necessary to obtain the correct segmentation of both tissue and gold particles. This method will be used for the 3D localization of deposited particles in the gas-exchange area of the lung.

  6. Strain-dependent Damage in Mouse Lung After Carbon Ion Irradiation

    SciTech Connect (OSTI)

    Moritake, Takashi; Proton Medical Research Center, University of Tsukuba, Tsukuba ; Fujita, Hidetoshi; Yanagisawa, Mitsuru; Nakawatari, Miyako; Imadome, Kaori; Nakamura, Etsuko; Iwakawa, Mayumi; Imai, Takashi

    2012-09-01

    Purpose: To examine whether inherent factors produce differences in lung morbidity in response to carbon ion (C-ion) irradiation, and to identify the molecules that have a key role in strain-dependent adverse effects in the lung. Methods and Materials: Three strains of female mice (C3H/He Slc, C57BL/6J Jms Slc, and A/J Jms Slc) were locally irradiated in the thorax with either C-ion beams (290 MeV/n, in 6 cm spread-out Bragg peak) or with {sup 137}Cs {gamma}-rays as a reference beam. We performed survival assays and histologic examination of the lung with hematoxylin-eosin and Masson's trichrome staining. In addition, we performed immunohistochemical staining for hyaluronic acid (HA), CD44, and Mac3 and assayed for gene expression. Results: The survival data in mice showed a between-strain variance after C-ion irradiation with 10 Gy. The median survival time of C3H/He was significantly shortened after C-ion irradiation at the higher dose of 12.5 Gy. Histologic examination revealed early-phase hemorrhagic pneumonitis in C3H/He and late-phase focal fibrotic lesions in C57BL/6J after C-ion irradiation with 10 Gy. Pleural effusion was apparent in C57BL/6J and A/J mice, 168 days after C-ion irradiation with 10 Gy. Microarray analysis of irradiated lung tissue in the three mouse strains identified differential expression changes in growth differentiation factor 15 (Gdf15), which regulates macrophage function, and hyaluronan synthase 1 (Has1), which plays a role in HA metabolism. Immunohistochemistry showed that the number of CD44-positive cells, a surrogate marker for HA accumulation, and Mac3-positive cells, a marker for macrophage infiltration in irradiated lung, varied significantly among the three mouse strains during the early phase. Conclusions: This study demonstrated a strain-dependent differential response in mice to C-ion thoracic irradiation. Our findings identified candidate molecules that could be implicated in the between-strain variance to early hemorrhagic pneumonitis after C-ion irradiation.

  7. CDK-associated Cullin 1 promotes cell proliferation with activation of ERK1/2 in human lung cancer A549 cells

    SciTech Connect (OSTI)

    Chen, Tian Jun; Gao, Fei; Yang, Tian; Thakur, Asmitanand; Ren, Hui; Li, Yang; Zhang, Shuo; Wang, Ting; Chen, Ming Wei

    2013-07-19

    Highlights: CDK-associated Cullin 1 (CAC1) expression increases in human lung carcinoma. CAC1 promotes the proliferation of lung cancer A549 cells. CAC1 promotes human lung cancer A549 cell proliferation with activation of ERK1/2. -- Abstract: Lung cancer is one of the most common causes of cancer-related death in the world, but the mechanisms remain unknown. In this study, we investigated the expression of CDK-associated Cullin 1 (CAC1) in lung cancer, the effect of CAC1 on the proliferation of human lung cancer A549 cells, and the activation of signaling pathways of mitogen-activated protein kinases (MAPKs). Results showed that CAC1 expression was higher levels in human lung carcinoma than normal lung tissue, and CAC1 siRNA reduced the proliferation of lung cancer A549 cells by decreasing cell activity and cell division in vitro. The proportion of cells treated with CAC1 siRNA increased in the G1 phase and decreased in the S and G2/M phase, indicative of G1 cell cycle arrest. Furthermore, the proportions of early/late apoptosis in lung cancer A549 cells were enhanced with CAC1 siRNA treatment. It was also found that activation of extracellular signal-regulated protein kinase (ERK) and p38 signaling pathways were involved in the proliferation of A549 cells. After CAC1 siRNA treatment, p-ERK1/2 levels decreased, and meanwhile p-p38 level increased, A549 cell proliferation increased when ERK1/2 signaling is activated by PMA. Our findings demonstrated that CAC1 promoted the proliferation of human lung cancer A549 cells with activation of ERK1/2 signaling pathways, suggesting a potential cure target for treatment of human lung cancer.

  8. Silencing of poly(ADP-ribose) glycohydrolase sensitizes lung cancer cells to radiation through the abrogation of DNA damage checkpoint

    SciTech Connect (OSTI)

    Nakadate, Yusuke; Department of Bioengineering, Graduate School of Engineering, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585 ; Kodera, Yasuo; Kitamura, Yuka; Tachibana, Taro; Tamura, Tomohide; Koizumi, Fumiaki

    2013-11-29

    Highlights: Radiosensitization by PARG silencing was observed in multiple lung cancer cells. PAR accumulation was enhanced by PARG silencing after DNA damage. Radiation-induced G2/M arrest and checkpoint activation were impaired by PARG siRNA. -- Abstract: Poly(ADP-ribose) glycohydrolase (PARG) is a major enzyme that plays a role in the degradation of poly(ADP-ribose) (PAR). PARG deficiency reportedly sensitizes cells to the effects of radiation. In lung cancer, however, it has not been fully elucidated. Here, we investigated whether PARG siRNA contributes to an increased radiosensitivity using 8 lung cancer cell lines. Among them, the silencing of PARG induced a radiosensitizing effect in 5 cell lines. Radiation-induced G2/M arrest was largely suppressed by PARG siRNA in PC-14 and A427 cells, which exhibited significantly enhanced radiosensitivity in response to PARG knockdown. On the other hand, a similar effect was not observed in H520 cells, which did not exhibit a radiosensitizing effect. Consistent with a cell cycle analysis, radiation-induced checkpoint signals were not well activated in the PC-14 and A427 cells when treated with PARG siRNA. These results suggest that the increased sensitivity to radiation induced by PARG knockdown occurs through the abrogation of radiation-induced G2/M arrest and checkpoint activation in lung cancer cells. Our findings indicate that PARG could be a potential target for lung cancer treatments when used in combination with radiotherapy.

  9. Dynamic MRI of Grid-Tagged Hyperpolarized Helium-3 for the Assessment of Lung Motion During Breathing

    SciTech Connect (OSTI)

    Cai Jing; Sheng Ke; Benedict, Stanley H.; Read, Paul W.; Larner, James M.; Mugler, John P.; Lange, Eduard E. de; Cates, Gordon D.; Miller, G. Wilson

    2009-09-01

    Purpose: To develop a dynamic magnetic resonance imaging (MRI) tagging technique using hyperpolarized helium-3 (HP He-3) to track lung motion. Methods and Materials: An accelerated non-Cartesian k-space trajectory was used to gain acquisition speed, at the cost of introducing image artifacts, providing a viable strategy for obtaining whole-lung coverage with adequate temporal resolution. Multiple-slice two-dimensional dynamic images of the lung were obtained in three healthy subjects after inhaling He-3 gas polarized to 35%-40%. Displacement, strain, and ventilation maps were computed from the observed motion of the grid peaks. Results: Both temporal and spatial variations of pulmonary mechanics were observed in normal subjects, including shear motion between different lobes of the same lung. Conclusion: These initial results suggest that dynamic imaging of grid-tagged hyperpolarized magnetization may potentially be a powerful tool for observing and quantifying pulmonary biomechanics on a regional basis and for assessing, validating, and improving lung deformable image registration algorithms.

  10. Diet-Induced Obesity Reprograms the Inflammatory Response of the Murine Lung to Inhaled Endotoxin

    SciTech Connect (OSTI)

    Tilton, Susan C.; Waters, Katrina M.; Karin, Norman J.; Webb-Robertson, Bobbie-Jo M.; Zangar, Richard C.; Lee, Monika K.; Bigelow, Diana J.; Pounds, Joel G.; Corley, Richard A.

    2013-03-01

    The co-occurrence of environmental factors is common in complex human diseases and, as such, understanding the molecular responses involved is essential to determine risk and susceptibility to disease. We have investigated the key biological pathways that define susceptibility for pulmonary infection during obesity in diet-induced obese (DIO) and regular weight (RW) C57BL/6 mice exposed to inhaled lipopolysaccharide (LPS). LPS induced a strong inflammatory response in all mice as indicated by elevated cell counts of macrophages and neutrophils and levels of proinflammatory cytokines (MDC, MIP-1?, IL-12, RANTES) in the bronchoalveolar lavage fluid. Additionally, DIO mice exhibited 50% greater macrophage cell counts, but decreased levels of the cytokines, IL-6, TARC, TNF-?, and VEGF relative to RW mice. Microarray analysis of lung tissue showed over half of the LPS-induced expression in DIO mice consisted of genes unique for obese mice, suggesting that obesity reprograms how the lung responds to subsequent insult. In particular, we found that obese animals exposed to LPS have gene signatures showing increased inflammatory and oxidative stress response and decreased antioxidant capacity compared with RW. Because signaling pathways for these responses can be common to various sources of environmentally induced lung damage, we further identified biomarkers that are indicative of specific toxicant exposure by comparing gene signatures after LPS exposure to those from a parallel study with cigarette smoke. These data show obesity may increase sensitivity to further insult and that co-occurrence of environmental stressors result in complex biosignatures that are not predicted from analysis of individual exposures.

  11. On using an adaptive neural network to predict lung tumor motion during respiration for radiotherapy applications

    SciTech Connect (OSTI)

    Isaksson, Marcus; Jalden, Joakim; Murphy, Martin J.

    2005-12-15

    In this study we address the problem of predicting the position of a moving lung tumor during respiration on the basis of external breathing signals--a technique used for beam gating, tracking, and other dynamic motion management techniques in radiation therapy. We demonstrate the use of neural network filters to correlate tumor position with external surrogate markers while simultaneously predicting the motion ahead in time, for situations in which neither the breathing pattern nor the correlation between moving anatomical elements is constant in time. One pancreatic cancer patient and two lung cancer patients with mid/upper lobe tumors were fluoroscopically imaged to observe tumor motion synchronously with the movement of external chest markers during free breathing. The external marker position was provided as input to a feed-forward neural network that correlated the marker and tumor movement to predict the tumor position up to 800 ms in advance. The predicted tumor position was compared to its observed position to establish the accuracy with which the filter could dynamically track tumor motion under nonstationary conditions. These results were compared to simplified linear versions of the filter. The two lung cancer patients exhibited complex respiratory behavior in which the correlation between surrogate marker and tumor position changed with each cycle of breathing. By automatically and continuously adjusting its parameters to the observations, the neural network achieved better tracking accuracy than the fixed and adaptive linear filters. Variability and instability in human respiration complicate the task of predicting tumor position from surrogate breathing signals. Our results show that adaptive signal-processing filters can provide more accurate tumor position estimates than simpler stationary filters when presented with nonstationary breathing motion.

  12. SU-E-T-170: Evaluation of Rotational Errors in Proton Therapy Planning of Lung Cancer

    SciTech Connect (OSTI)

    Rana, S; Zhao, L; Ramirez, E; Singh, H; Zheng, Y

    2014-06-01

    Purpose: To investigate the impact of rotational (roll, yaw, and pitch) errors in proton therapy planning of lung cancer. Methods: A lung cancer case treated at our center was used in this retrospective study. The original plan was generated using two proton fields (posterior-anterior and left-lateral) with XiO treatment planning system (TPS) and delivered using uniform scanning proton therapy system. First, the computed tomography (CT) set of original lung treatment plan was re-sampled for rotational (roll, yaw, and pitch) angles ranged from ?5 to +5, with an increment of 2.5. Second, 12 new proton plans were generated in XiO using the 12 re-sampled CT datasets. The same beam conditions, isocenter, and devices were used in new treatment plans as in the original plan. All 12 new proton plans were compared with original plan for planning target volume (PTV) coverage and maximum dose to spinal cord (cord Dmax). Results: PTV coverage was reduced in all 12 new proton plans when compared to that of original plan. Specifically, PTV coverage was reduced by 0.03% to 1.22% for roll, by 0.05% to 1.14% for yaw, and by 0.10% to 3.22% for pitch errors. In comparison to original plan, the cord Dmax in new proton plans was reduced by 8.21% to 25.81% for +2.5 to +5 pitch, by 5.28% to 20.71% for +2.5 to +5 yaw, and by 5.28% to 14.47% for ?2.5 to ?5 roll. In contrast, cord Dmax was increased by 3.80% to 3.86% for ?2.5 to ?5 pitch, by 0.63% to 3.25% for ?2.5 to ?5 yaw, and by 3.75% to 4.54% for +2.5 to +5 roll. Conclusion: PTV coverage was reduced by up to 3.22% for rotational error of 5. The cord Dmax could increase or decrease depending on the direction of rotational error, beam angles, and the location of lung tumor.

  13. On the interplay effects with proton scanning beams in stage III lung cancer

    SciTech Connect (OSTI)

    Li, Yupeng; Kardar, Laleh; Liao, Li; Lim, Gino; Li, Xiaoqiang; Li, Heng; Zhu, Ronald X.; Sahoo, Narayan; Gillin, Michael; Zhang, Xiaodong; Cao, Wenhua; Chang, Joe Y.; Liao, Zhongxing; Komaki, Ritsuko; Cox, James D.

    2014-02-15

    Purpose: To assess the dosimetric impact of interplay between spot-scanning proton beam and respiratory motion in intensity-modulated proton therapy (IMPT) for stage III lung cancer. Methods: Eleven patients were sampled from 112 patients with stage III nonsmall cell lung cancer to well represent the distribution of 112 patients in terms of target size and motion. Clinical target volumes (CTVs) and planning target volumes (PTVs) were defined according to the authors' clinical protocol. Uniform and realistic breathing patterns were considered along with regular- and hypofractionation scenarios. The dose contributed by a spot was fully calculated on the computed tomography (CT) images corresponding to the respiratory phase that the spot is delivered, and then accumulated to the reference phase of the 4DCT to generate the dynamic dose that provides an estimation of what might be delivered under the influence of interplay effect. The dynamic dose distributions at different numbers of fractions were compared with the corresponding 4D composite dose which is the equally weighted average of the doses, respectively, computed on respiratory phases of a 4DCT image set. Results: Under regular fractionation, the average and maximum differences in CTV coverage between the 4D composite and dynamic doses after delivery of all 35 fractions were no more than 0.2% and 0.9%, respectively. The maximum differences between the two dose distributions for the maximum dose to the spinal cord, heart V40, esophagus V55, and lung V20 were 1.2 Gy, 0.1%, 0.8%, and 0.4%, respectively. Although relatively large differences in single fraction, correlated with small CTVs relative to motions, were observed, the authors' biological response calculations suggested that this interfractional dose variation may have limited biological impact. Assuming a hypofractionation scenario, the differences between the 4D composite and dynamic doses were well confined even for single fraction. Conclusions: Despite the presence of interplay effect, the delivered dose may be reliably estimated using the 4D composite dose. In general the interplay effect may not be a primary concern with IMPT for lung cancers for the authors' institution. The described interplay analysis tool may be used to provide additional confidence in treatment delivery.

  14. Lung autophagic response following exposure of mice to whole body irradiation, with and without amifostine

    SciTech Connect (OSTI)

    Zois, Christos E.; Giatromanolaki, Alexandra; Kainulainen, Heikki; Botaitis, Sotirios; Torvinen, Sira; Simopoulos, Constantinos; Kortsaris, Alexandros; Sivridis, Efthimios; Koukourakis, Michael I.

    2011-01-07

    Research highlights: {yields} We investigated the effect 6 Gy of WBI on the autophagic machinery of normal mouse lung. {yields} Irradiation induces dysfunction of the autophagic machinery in normal lung, characterized by decreased transcription of the LC3A/Beclin-1 mRNA and accumulation of the LC3A, and p62 proteins. {yields} The membrane bound LC3A-II protein levels increased in the cytosolic fraction (not in the pellet), contrasting the patterns noted after starvation-induced autophagy. {yields} Administration of amifostine, reversed all the LC3A and p62 findings, suggesting protection of the normal autophagic function. -- Abstract: Purpose: The effect of ionizing irradiation on the autophagic response of normal tissues is largely unexplored. Abnormal autophagic function may interfere the protein quality control leading to cell degeneration and dysfunction. This study investigates its effect on the autophagic machinery of normal mouse lung. Methods and materials: Mice were exposed to 6 Gy of whole body {gamma}-radiation and sacrificed at various time points. The expression of MAP1LC3A/LC3A/Atg8, beclin-1, p62/sequestosome-1 and of the Bnip3 proteins was analyzed. Results: Following irradiation, the LC3A-I and LC3A-II protein levels increased significantly at 72 h and 7 days. Strikingly, LC3A-II protein was increased (5.6-fold at 7 days; p < 0.001) only in the cytosolic fraction, but remained unchanged in the membrane fraction. The p62 protein, was significantly increased in both supernatant and pellet fraction (p < 0.001), suggesting an autophagosome turnover deregulation. These findings contrast the patterns of starvation-induced autophagy up-regulation. Beclin-1 levels remained unchanged. The Bnip3 protein was significantly increased at 8 h, but it sharply decreased at 72 h (p < 0.05). Administration of amifostine (200 mg/kg), 30 min before irradiation, reversed all the LC3A and p62 findings on blots, suggesting restoration of the normal autophagic function. The LC3A and Beclin1 mRNA levels significantly declined following irradiation (p < 0.01), whereas Bnip3 levels increased. Conclusions: It is suggested that irradiation induces dysfunction of the autophagic machinery in normal lung, characterized by decreased transcription of the LC3A/Beclin-1 mRNA and accumulation of the LC3A, and p62 proteins. Whether this is due to defective maturation or to aberrant degradation of the autophagosomes requires further investigation.

  15. Method of using 5,10,15,20-tetrakis(carboxyphenyl)porphine for detecting cancers of the lung

    DOE Patents [OSTI]

    Cole, D.A.; Moody, D.C. III; Ellinwood, L.E.; Klein, M.G.

    1992-11-10

    A method is described for using tetra-aryl porphyrins for and, in particular, 5,10,15,20-tetrakis(4-carboxyphenyl)porphine as a fluorescent tracer for cancers of the lung, and as a radiotracer therefor as a complex with [sup 67]Cu. The latter complex also provides a source of beta radiation for selective destruction of lung malignancies as well as gamma radiation useful for image analysis of the lungs by single photon emission computed tomography, as an example, both in vivo. Copper-64 may be substituted for the [sup 67]Cu if only radiotracer characteristics are of interest. This lighter isotope of copper is a positron emitter, and positron emission tomography techniques can be used to locate the malignant tissue mass. 1 figure.

  16. TU-A-12A-01: Consistency of Lung Expansion and Contraction During Respiration: Implications for Quantitative Imaging

    SciTech Connect (OSTI)

    Patton, T; Du, K; Bayouth, J; Christensen, G; Reinhardt, J

    2014-06-15

    Purpose: Four-dimensional computed tomography (4DCT) can be used to evaluate longitudinal changes in pulmonary function. The sensitivity of such measurements to identify function change may be improved with reproducible breathing patterns. The purpose of this study was to determine if inhale was more consistent than exhale, i.e., lung expansion during inhalation compared to lung contraction during exhalation. Methods: Repeat 4DCT image data acquired within a short time interval from 8 patients. Using a tissue volume preserving deformable image registration algorithm, Jacobian ventilation maps in two scanning sessions were computed and compared on the same coordinate for reproducibility analysis. Equivalent lung volumes (ELV) were used for 5 subjects and equivalent title volumes (ETV) for the 3 subjects who experienced a baseline shift between scans. In addition, gamma pass rate was calculated from a modified gamma index evaluation between two ventilation maps, using acceptance criterions of 2mm distance-to-agreement and 5% ventilation difference. The gamma pass rates were then compared using paired t-test to determine if there was a significant difference. Results: Inhalation was more reproducible than exhalation. In the 5 ELV subjects 78.5% of the lung voxels met the gamma criteria for expansion during inhalation when comparing the two scans, while significantly fewer (70.9% of the lung voxels) met the gamma criteria for contraction during exhalation (p = .027). In the 8 total subjects analyzed the average gamma pass rate for expansion during inhalation was 75.2% while for contraction during exhalation it was 70.3%; which trended towards significant (p = .064). Conclusion: This work implies inhalation is more reproducible than exhalation, when equivalent respiratory volumes are considered. The reason for this difference is unknown. Longitudinal investigation of pulmonary function change based on inhalation images appears appropriate for Jacobian-based measure of lung tissue expansion. NIH Grant: R01 CA166703.

  17. SU-E-J-87: Lung Deformable Image Registration Using Surface Mesh Deformation for Dose Distribution Combination

    SciTech Connect (OSTI)

    Labine, A; Carrier, J; Bedwani, S; Chav, R; DeGuise, J

    2014-06-01

    Purpose: To allow a reliable deformable image registration (DIR) method for dose calculation in radiation therapy. This work proposes a performance assessment of a morphological segmentation algorithm that generates a deformation field from lung surface displacements with 4DCT datasets. Methods: From the 4DCT scans of 15 selected patients, the deep exhale phase of the breathing cycle is identified as the reference scan. Varian TPS EclipseTM is used to draw lung contours, which are given as input to the morphological segmentation algorithm. Voxelized contours are smoothed by a Gaussian filter and then transformed into a surface mesh representation. Such mesh is adapted by rigid and elastic deformations to match each subsequent lung volumes. The segmentation efficiency is assessed by comparing the segmented lung contour and the TPS contour considering two volume metrics, defined as Volumetric Overlap Error (VOE) [%] and Relative Volume Difference (RVD) [%] and three surface metrics, defined as Average Symmetric Surface Distance (ASSD) [mm], Root Mean Square Symmetric Surface Distance (RMSSD) [mm] and Maximum Symmetric Surface Distance (MSSD) [mm]. Then, the surface deformation between two breathing phases is determined by the displacement of corresponding vertices in each deformed surface. The lung surface deformation is linearly propagated in the lung volume to generate 3D deformation fields for each breathing phase. Results: The metrics were averaged over the 15 patients and calculated with the same segmentation parameters. The volume metrics obtained are a VOE of 5.2% and a RVD of 2.6%. The surface metrics computed are an ASSD of 0.5 mm, a RMSSD of 0.8 mm and a MSSD of 6.9 mm. Conclusion: This study shows that the morphological segmentation algorithm can provide an automatic method to capture an organ motion from 4DCT scans and translate it into a volume deformation grid needed by DIR method for dose distribution combination.

  18. Dissolution and clearance of titanium tritide particles in the lungs of F344/Crl rats

    SciTech Connect (OSTI)

    Cheng, Yung-Sung; Snipes, M.B.; Wang, Yansheng

    1995-12-01

    Metal tritides are compounds in which the radioactive isotope tritium, following adsorption onto the metal, forms a stable chemical compound with the metal. When particles of tritiated metals become airborne, they can be inhaled by workers. Because the particles may be retained in the lung for extended periods, the resulting dose will be greater than doses following exposure to tritium gas or tritium oxide (HTO). Particles of triated metals may be dispersed into the air during routine handling, disruption of contaminated metals, or as a result of spontaneous radioactive decay processes. Unlike metal hydrides and deuterides, tritides are radioactive, and the decay of the tritium atoms affects the metal. Because helium is a product of the decay, helium bubbles form within the metal tritide matrix. The pressure from these bubbles leads to respirable particles breaking off from the tritide surface. Our results show that a substantial amount of titanium tritide remains in the rat lung 10 d after intratracheal instillation, confirming results previously obtain in an in vitro dissolution study.

  19. Chlorobenzene induces oxidative stress in human lung epithelial cells in vitro

    SciTech Connect (OSTI)

    Feltens, Ralph; Moegel, Iljana; Roeder-Stolinski, Carmen; Simon, Jan-Christoph; Herberth, Gunda; Lehmann, Irina

    2010-01-01

    Chlorobenzene is a volatile organic compound (VOC) that is widely used as a solvent, degreasing agent and chemical intermediate in many industrial settings. Occupational studies have shown that acute and chronic exposure to chlorobenzene can cause irritation of the mucosa of the upper respiratory tract and eyes. Using in vitro assays, we have shown in a previous study that human bronchial epithelial cells release inflammatory mediators such as the cytokine monocyte chemoattractant protein-1 (MCP-1) in response to chlorobenzene. This response is mediated through the NF-kappaB signaling pathway. Here, we investigated the effects of monochlorobenzene on human lung cells, with emphasis on potential alterations of the redox equilibrium to clarify whether the chlorobenzene-induced inflammatory response in lung epithelial cells is caused via an oxidative stress-dependent mechanism. We found that expression of cellular markers for oxidative stress, such as heme oxygenase 1 (HO-1), glutathione S-transferase pi1 (GSTP1), superoxide dismutase 1 (SOD1), prostaglandin-endoperoxide synthase 2 (PTGS2) and dual specificity phosphatase 1 (DUSP1), were elevated in the presence of monochlorobenzene. Likewise, intracellular reactive oxygen species (ROS) were increased in response to exposure. However, in the presence of the antioxidants N-(2-mercaptopropionyl)-glycine (MPG) or bucillamine, chlorobenzene-induced upregulation of marker proteins and release of the inflammatory mediator MCP-1 are suppressed. These results complement our previous findings and point to an oxidative stress-mediated inflammatory response following chlorobenzene exposure.

  20. Continuum-kinetic-microscopic model of lung clearance due to core-annular fluid entrainment

    SciTech Connect (OSTI)

    Mitran, Sorin

    2013-07-01

    The human lung is protected against aspirated infectious and toxic agents by a thin liquid layer lining the interior of the airways. This airway surface liquid is a bilayer composed of a viscoelastic mucus layer supported by a fluid film known as the periciliary liquid. The viscoelastic behavior of the mucus layer is principally due to long-chain polymers known as mucins. The airway surface liquid is cleared from the lung by ciliary transport, surface tension gradients, and airflow shear forces. This work presents a multiscale model of the effect of airflow shear forces, as exerted by tidal breathing and cough, upon clearance. The composition of the mucus layer is complex and variable in time. To avoid the restrictions imposed by adopting a viscoelastic flow model of limited validity, a multiscale computational model is introduced in which the continuum-level properties of the airway surface liquid are determined by microscopic simulation of long-chain polymers. A bridge between microscopic and continuum levels is constructed through a kinetic-level probability density function describing polymer chain configurations. The overall multiscale framework is especially suited to biological problems due to the flexibility afforded in specifying microscopic constituents, and examining the effects of various constituents upon overall mucus transport at the continuum scale.

  1. Cytogenetic damage in lymphocytes of patients undergoing therapy for small cell lung cancer and ovarian carcinoma

    SciTech Connect (OSTI)

    Padjas, Anna; Lesisz, Dominika; Lankoff, Anna; Banasik, Anna; Lisowska, Halina; Bakalarz, Robert; Gozdz, Stanislaw; Wojcik, Andrzej . E-mail: awojcik@pu.kielce.pl

    2005-12-01

    The level of cytogenetic damage in peripheral blood lymphocytes of patients undergoing chemotherapy has been analyzed incisively 20 years ago. The results showed that the highest level of cytogenetic damage was observed at the end of therapy. In recent years, the doses of anticancer drugs were intensified thanks to the discovery of colony stimulating factors. Therefore, it was interesting to analyze the kinetics of micronuclei formation in lymphocytes of patients undergoing modern chemotherapy. The frequencies of micronuclei were measured in lymphocytes of 6 patients with small cell lung cancer treated with a combination of cisplatin and etoposide and 7 patients with ovarian carcinoma treated with a combination of taxol and cisplatin. 3 patients with lung cancer received radiotherapy in addition to chemotherapy. Micronuclei were analyzed in lymphocytes collected before the start of therapy and 1 day before each following cycle of chemotherapy. The micronucleus frequencies were compared with the kinetics of leukocyte counts. The micronucleus frequencies showed an interindividual variability. On average, the frequencies of micronuclei increased during the first half of therapy and declined thereafter, reaching, in some patients with ovarian carcinoma, values below the pre-treatment level. Leukocyte counts decreased strongly at the beginning of therapy with an upward trend at the end. We suggest that the decline of micronuclei was due to repopulation of lymphocytes and acquired drug resistance.

  2. Modeling Local Control After Hypofractionated Stereotactic Body Radiation Therapy for Stage I Non-Small Cell Lung Cancer: A Report From the Elekta Collaborative Lung Research Group

    SciTech Connect (OSTI)

    Ohri, Nitin; Werner-Wasik, Maria; Grills, Inga S.; Belderbos, Jose; Hope, Andrew; Yan Di; Kestin, Larry L.; Guckenberger, Matthias; Sonke, Jan-Jakob; Bissonnette, Jean-Pierre; Xiao, Ying

    2012-11-01

    Purpose: Hypofractionated stereotactic body radiation therapy (SBRT) has emerged as an effective treatment option for early-stage non-small cell lung cancer (NSCLC). Using data collected by the Elekta Lung Research Group, we generated a tumor control probability (TCP) model that predicts 2-year local control after SBRT as a function of biologically effective dose (BED) and tumor size. Methods and Materials: We formulated our TCP model as follows: TCP = e{sup [BED10-c Asterisk-Operator L-TCD50]/k} Division-Sign (1 + e{sup [BED10-c Asterisk-Operator L-TCD50]/k}), where BED10 is the biologically effective SBRT dose, c is a constant, L is the maximal tumor diameter, and TCD50 and k are parameters that define the shape of the TCP curve. Least-squares optimization with a bootstrap resampling approach was used to identify the values of c, TCD50, and k that provided the best fit with observed actuarial 2-year local control rates. Results: Data from 504 NSCLC tumors treated with a variety of SBRT schedules were available. The mean follow-up time was 18.4 months, and 26 local recurrences were observed. The optimal values for c, TCD50, and k were 10 Gy/cm, 0 Gy, and 31 Gy, respectively. Thus, size-adjusted BED (sBED) may be defined as BED minus 10 times the tumor diameter (in centimeters). Our TCP model indicates that sBED values of 44 Gy, 69 Gy, and 93 Gy provide 80%, 90%, and 95% chances of tumor control at 2 years, respectively. When patients were grouped by sBED, the model accurately characterized the relationship between sBED and actuarial 2-year local control (r=0.847, P=.008). Conclusion: We have developed a TCP model that predicts 2-year local control rate after hypofractionated SBRT for early-stage NSCLC as a function of biologically effective dose and tumor diameter. Further testing of this model with additional datasets is warranted.

  3. Biodiesel versus diesel exposure: Enhanced pulmonary inflammation, oxidative stress, and differential morphological changes in the mouse lung

    SciTech Connect (OSTI)

    Yanamala, Naveena; Birch, M. Eileen; Kisin, Elena; Bugarski, Aleksandar D.

    2013-10-15

    The use of biodiesel (BD) or its blends with petroleum diesel (D) is considered to be a viable approach to reduce occupational and environmental exposures to particulate matter (PM). Due to its lower particulate mass emissions compared to D, use of BD is thought to alleviate adverse health effects. Considering BD fuel is mainly composed of unsaturated fatty acids, we hypothesize that BD exhaust particles could induce pronounced adverse outcomes, due to their ability to readily oxidize. The main objective of this study was to compare the effects of particles generated by engine fueled with neat BD and neat petroleum-based D. Biomarkers of tissue damage and inflammation were significantly elevated in lungs of mice exposed to BD particulates. Additionally, BD particulates caused a significant accumulation of oxidatively modified proteins and an increase in 4-hydroxynonenal. The up-regulation of inflammatory cytokines/chemokines/growth factors was higher in lungs upon BD particulate exposure. Histological evaluation of lung sections indicated presence of lymphocytic infiltrate and impaired clearance with prolonged retention of BD particulate in pigment laden macrophages. Taken together, these results clearly indicate that BD exhaust particles could exert more toxic effects compared to D. - Highlights: Exposure of mice to BDPM caused higher pulmonary toxicity compared to DPM. Oxidative stress and inflammation were higher in BD vs to D exposed mice. Inflammatory lymphocyte infiltrates were seen only in lungs of mice exposed to BD. Ineffective clearance, prolonged PM retention was present only after BD exposure.

  4. TH-E-17A-10: Markerless Lung Tumor Tracking Based On Beams Eye View EPID Images

    SciTech Connect (OSTI)

    Chiu, T; Kearney, V; Liu, H; Jiang, L; Foster, R; Mao, W; Rozario, T; Bereg, S; Klash, S

    2014-06-15

    Purpose: Dynamic tumor tracking or motion compensation techniques have proposed to modify beam delivery following lung tumor motion on the flight. Conventional treatment plan QA could be performed in advance since every delivery may be different. Markerless lung tumor tracking using beams eye view EPID images provides a best treatment evaluation mechanism. The purpose of this study is to improve the accuracy of the online markerless lung tumor motion tracking method. Methods: The lung tumor could be located on every frame of MV images during radiation therapy treatment by comparing with corresponding digitally reconstructed radiograph (DRR). A kV-MV CT corresponding curve is applied on planning kV CT to generate MV CT images for patients in order to enhance the similarity between DRRs and MV treatment images. This kV-MV CT corresponding curve was obtained by scanning a same CT electron density phantom by a kV CT scanner and MV scanner (Tomotherapy) or MV CBCT. Two sets of MV DRRs were then generated for tumor and anatomy without tumor as the references to tracking the tumor on beams eye view EPID images. Results: Phantom studies were performed on a Varian TrueBeam linac. MV treatment images were acquired continuously during each treatment beam delivery at 12 gantry angles by iTools. Markerless tumor tracking was applied with DRRs generated from simulated MVCT. Tumors were tracked on every frame of images and compared with expected positions based on programed phantom motion. It was found that the average tracking error were 2.3 mm. Conclusion: This algorithm is capable of detecting lung tumors at complicated environment without implanting markers. It should be noted that the CT data has a slice thickness of 3 mm. This shows the statistical accuracy is better than the spatial accuracy. This project has been supported by a Varian Research Grant.

  5. Individualized Radical Radiotherapy of Non-Small-Cell Lung Cancer Based on Normal Tissue Dose Constraints: A Feasibility Study

    SciTech Connect (OSTI)

    Baardwijk, Angela van Bosmans, Geert; Boersma, Liesbeth; Wanders, Stofferinus; Dekker, Andre; Dingemans, Anne Marie C.; Bootsma, Gerben; Geraedts, Wiel; Pitz, Cordula; Simons, Jean; Lambin, Philippe; Ruysscher, Dirk de

    2008-08-01

    Purpose: Local recurrence is a major problem after (chemo-)radiation for non-small-cell lung cancer. We hypothesized that for each individual patient, the highest therapeutic ratio could be achieved by increasing total tumor dose (TTD) to the limits of normal tissues, delivered within 5 weeks. We report first results of a prospective feasibility trial. Methods and Materials: Twenty-eight patients with medically inoperable or locally advanced non-small-cell lung cancer, World Health Organization performance score of 0-1, and reasonable lung function (forced expiratory volume in 1 second > 50%) were analyzed. All patients underwent irradiation using an individualized prescribed TTD based on normal tissue dose constraints (mean lung dose, 19 Gy; maximal spinal cord dose, 54 Gy) up to a maximal TTD of 79.2 Gy in 1.8-Gy fractions twice daily. No concurrent chemoradiation was administered. Toxicity was scored using the Common Terminology Criteria for Adverse Events criteria. An {sup 18}F-fluoro-2-deoxy-glucose-positron emission tomography-computed tomography scan was performed to evaluate (metabolic) response 3 months after treatment. Results: Mean delivered dose was 63.0 {+-} 9.8 Gy. The TTD was most often limited by the mean lung dose (32.1%) or spinal cord (28.6%). Acute toxicity generally was mild; only 1 patient experienced Grade 3 cough and 1 patient experienced Grade 3 dysphagia. One patient (3.6%) died of pneumonitis. For late toxicity, 2 patients (7.7%) had Grade 3 cough or dyspnea; none had severe dysphagia. Complete metabolic response was obtained in 44% (11 of 26 patients). With a median follow-up of 13 months, median overall survival was 19.6 months, with a 1-year survival rate of 57.1%. Conclusions: Individualized maximal tolerable dose irradiation based on normal tissue dose constraints is feasible, and initial results are promising.

  6. Complications associated with brachytherapy alone or with laser in lung cancer

    SciTech Connect (OSTI)

    Khanavkar, B.; Stern, P.; Alberti, W.; Nakhosteen, J.A. )

    1991-05-01

    Relatively little has been reported about destruction through brachytherapy of mucosa-perforating and extraluminary tumors with probable large vessel involvement causing major hemorrhagic or fistular complications. We report 12 patients subjected to laser and brachytherapy for centrally occluding lung cancer, whom we have periodically followed up from June 1986 until they died. Although all laser procedures were free from complications, necrotic cavitation in five cases, two of which were accompanied by large bronchoesophageal fistulas, and massive fatal hemoptysis occurred in six. Minor complications included radiation mucositis (two), noncritical mucosal scarring (two), and cough (four). Characteristics that will identify patients at risk of developing fatal hemoptysis and fistulas should be better defined by imaging and endoscopic techniques. In such cases, modifying the protocol or using alternative procedures should be considered. Minor complications, such as cough, can be avoided by using topical steroid therapy (eg, beclomethasone dipropionate).

  7. SU-E-P-03: Implementing a Low Dose Lung Screening CT Program Meeting Regulatory Requirements

    SciTech Connect (OSTI)

    LaFrance, M; Marsh, S; O'Donnell, G

    2014-06-01

    Purpose: To provide information pertaining to IROC Houston QA Center's (RPC) credentialing process for institutions participating in NCI-sponsored clinical trials. Purpose: Provide guidance to the Radiology Departments with the intent of implementing a Low Dose CT Screening Program using different CT Scanners with multiple techniques within the framework of the required state regulations. Method: State Requirements for the purpose of implementing a Low Dose CT Lung Protocol required working with the Radiology and Pulmonary Department in setting up a Low Dose Screening Protocol designed to reduce the radiation burden to the patients enrolled. Radiation dose measurements (CTDIvol) for various CT manufacturers (Siemens16, Siemens 64, Philips 64, and Neusoft128) for three different weight based protocols. All scans were reviewed by the Radiologist. Prior to starting a low dose lung screening protocol, information had to be submitted to the state for approval. Performing a Healing Arts protocol requires extensive information. This not only includes name and address of the applicant but a detailed description of the disease, the x-ray examination and the population to be examined. The unit had to be tested by a qualified expert using the technique charts. The credentials of all the operators, the supervisors and the Radiologists had to be submitted to the state. Results: All the appropriate documentation was sent to the state for review. The measured results between the Low Dose Protocol versus the default Adult Chest Protocol showed that there was a dose reduction of 65% for small (100-150 lb.) patient, 75% for the Medium patient (151-250 lbs.), and a 55% reduction for the Large patient ( over 250 lbs.). Conclusion: Measured results indicated that the Low Dose Protocol indeed lowered the screening patient's radiation dose and the institution was able to submit the protocol to the State's regulators.

  8. Source apportionment of particulate matter in the US and associations with lung inflammatory markers

    SciTech Connect (OSTI)

    Duvall, R.M.; Norris, G.A.; Dailey, L.A.; Burke, J.M.; McGee, J.K.; Gilmour, M.I.; Gordon, T.; Devlin, R.B.

    2008-07-01

    Size-fractionated particulate matter (PM) samples were collected from six U.S. cities and chemically analyzed as part of the Multiple Air Pollutant Study. Particles were administered to cultured lung cells and the production of three different proinflammatory markers was measured to explore the association between the health effect markers and PM. Ultrafine, fine, and coarse PM samples were collected between December 2003 and May 2004 over a 4-wk period in each city. Filters were pooled for each city and the PM samples were extracted then analyzed for trace metals, ions, and elemental carbon. Particle extracts were applied to cultured human primary airway epithelial cells, and the secreted levels of interleukin-8 (IL-8), heme oxygenase-1, and cyclooxygenase-2 were measured 1 and 24 h following exposure. Fine PM sources were quantified by the chemical mass balance (CMB) model. The relationship between toxicological measures, PM sources, and individual species were evaluated using linear regression. Ultrafine and fine PM mass were associated with increases in IL-8 (r{sup 2} = .80 for ultrafine and r{sup 2} = .52 for fine). Sources of fine PM and their relative contributions varied across the sampling sites and a strong linear association was observed between IL-8 and secondary sulfate from coal combustion (r{sup 2} = .79). Ultrafine vanadium, lead, copper, and sulfate were also associated with increases in IL-8. Increases in inflammatory markers were not observed for coarse PM mass and source markers. These findings suggest that certain PM size fractions and sources are associated with markers of lung injury or inflammation.

  9. Accelerated cellular senescence phenotype of GAPDH-depleted human lung carcinoma cells

    SciTech Connect (OSTI)

    Phadke, Manali; Krynetskaia, Natalia; Mishra, Anurag; Krynetskiy, Evgeny; Jayne Haines Center for Pharmacogenomics, Temple University School of Pharmacy, Philadelphia, PA 19140

    2011-07-29

    Highlights: {yields} We examined the effect of glyceraldehyde 3-phosphate (GAPDH) depletion on proliferation of human carcinoma A549 cells. {yields} GAPDH depletion induces accelerated senescence in tumor cells via AMPK network, in the absence of DNA damage. {yields} Metabolic and genetic rescue experiments indicate that GAPDH has regulatory functions linking energy metabolism and cell cycle. {yields} Induction of senescence in LKB1-deficient lung cancer cells via GAPDH depletion suggests a novel strategy to control tumor cell proliferation. -- Abstract: Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a pivotal glycolytic enzyme, and a signaling molecule which acts at the interface between stress factors and the cellular apoptotic machinery. Earlier, we found that knockdown of GAPDH in human carcinoma cell lines resulted in cell proliferation arrest and chemoresistance to S phase-specific cytotoxic agents. To elucidate the mechanism by which GAPDH depletion arrests cell proliferation, we examined the effect of GAPDH knockdown on human carcinoma cells A549. Our results show that GAPDH-depleted cells establish senescence phenotype, as revealed by proliferation arrest, changes in morphology, SA-{beta}-galactosidase staining, and more than 2-fold up-regulation of senescence-associated genes DEC1 and GLB1. Accelerated senescence following GAPDH depletion results from compromised glycolysis and energy crisis leading to the sustained AMPK activation via phosphorylation of {alpha} subunit at Thr172. Our findings demonstrate that GAPDH depletion switches human tumor cells to senescent phenotype via AMPK network, in the absence of DNA damage. Rescue experiments using metabolic and genetic models confirmed that GAPDH has important regulatory functions linking the energy metabolism and the cell cycle networks. Induction of senescence in LKB1-deficient non-small cell lung cancer cells via GAPDH depletion suggests a novel strategy to control tumor cell proliferation.

  10. Volumetric Image Guidance Using Carina vs Spine as Registration Landmarks for Conventionally Fractionated Lung Radiotherapy

    SciTech Connect (OSTI)

    Lavoie, Caroline; Higgins, Jane; Bissonnette, Jean-Pierre; Le, Lisa W.; Sun, Alexander; Brade, Anthony; Hope, Andrew; Cho, John; Bezjak, Andrea

    2012-12-01

    Purpose: To compare the relative accuracy of 2 image guided radiation therapy methods using carina vs spine as landmarks and then to identify which landmark is superior relative to tumor coverage. Methods and Materials: For 98 lung patients, 2596 daily image-guidance cone-beam computed tomography scans were analyzed. Tattoos were used for initial patient alignment; then, spine and carina registrations were performed independently. A separate analysis assessed the adequacy of gross tumor volume, internal target volume, and planning target volume coverage on cone-beam computed tomography using the initial, middle, and final fractions of radiation therapy. Coverage was recorded for primary tumor (T), nodes (N), and combined target (T+N). Three scenarios were compared: tattoos alignment, spine registration, and carina registration. Results: Spine and carina registrations identified setup errors {>=}5 mm in 35% and 46% of fractions, respectively. The mean vector difference between spine and carina matching had a magnitude of 3.3 mm. Spine and carina improved combined target coverage, compared with tattoos, in 50% and 34% (spine) to 54% and 46% (carina) of the first and final fractions, respectively. Carina matching showed greater combined target coverage in 17% and 23% of fractions for the first and final fractions, respectively; with spine matching, this was only observed in 4% (first) and 6% (final) of fractions. Carina matching provided superior nodes coverage at the end of radiation compared with spine matching (P=.0006), without compromising primary tumor coverage. Conclusion: Frequent patient setup errors occur in locally advanced lung cancer patients. Spine and carina registrations improved combined target coverage throughout the treatment course, but carina matching provided superior combined target coverage.

  11. Combined therapeutic potential of nuclear receptors with receptor tyrosine kinase inhibitors in lung cancer

    SciTech Connect (OSTI)

    Wairagu, Peninah M.; Park, Kwang Hwa; Kim, Jihye; Choi, Jong-Whan; Kim, Hyun-Won; Yeh, Byung-Il; Jung, Soon-Hee; Yong, Suk-Joong; Jeong, Yangsik

    2014-05-09

    Highlights: The 48 NR genes and 48 biological anti-cancer targets are profiled in paired-cells. Growth inhibition by NR ligands or TKIs is target receptor level-dependent. T0901317 with gefitinib/PHA665752 shows additive growth inhibition in lung cells. - Abstract: Cancer heterogeneity is a big hurdle in achieving complete cancer treatment, which has led to the emergence of combinational therapy. In this study, we investigated the potential use of nuclear receptor (NR) ligands for combinational therapy with other anti-cancer drugs. We first profiled all 48 NRs and 48 biological anti-cancer targets in four pairs of lung cell lines, where each pair was obtained from the same patient. Two sets of cell lines were normal and the corresponding tumor cell lines while the other two sets consisted of primary versus metastatic tumor cell lines. Analysis of the expression profile revealed 11 NRs and 15 cancer targets from the two pairs of normal versus tumor cell lines, and 9 NRs and 9 cancer targets from the primary versus metastatic tumor cell lines had distinct expression patterns in each category. Finally, the evaluation of nuclear receptor ligand T0901317 for liver X receptor (LXR) demonstrated its combined therapeutic potential with tyrosine kinase inhibitors. The combined treatment of cMET inhibitor PHA665752 or EGFR inhibitor gefitinib with T0901317 showed additive growth inhibition in both H2073 and H1993 cells. Mechanistically, the combined treatment suppressed cell cycle progression by inhibiting cyclinD1 and cyclinB expression. Taken together, this study provides insight into the potential use of NR ligands in combined therapeutics with other biological anti-cancer drugs.

  12. Erlotinib Versus Radiation Therapy for Brain Metastases in Patients With EGFR-Mutant Lung Adenocarcinoma

    SciTech Connect (OSTI)

    Gerber, Naamit K.; Yamada, Yoshiya; Rimner, Andreas; Shi, Weiji; Riely, Gregory J.; Beal, Kathryn; Yu, Helena A.; Chan, Timothy A.; Zhang, Zhigang; Wu, Abraham J.

    2014-06-01

    Purpose/Objectives: Radiation therapy (RT) is the principal modality in the treatment of patients with brain metastases (BM). However, given the activity of EGFR tyrosine kinase inhibitors in the central nervous system, it is uncertain whether upfront brain RT is necessary for patients with EGFR-mutant lung adenocarcinoma with BM. Methods and Materials: Patients with EGFR-mutant lung adenocarcinoma and newly diagnosed BM were identified. Results: 222 patients were identified. Exclusion criteria included prior erlotinib use, presence of a de novo erlotinib resistance mutation, or incomplete data. Of the remaining 110 patients, 63 were treated with erlotinib, 32 with whole brain RT (WBRT), and 15 with stereotactic radiosurgery (SRS). The median overall survival (OS) for the whole cohort was 33 months. There was no significant difference in OS between the WBRT and erlotinib groups (median, 35 vs 26 months; P=.62), whereas patients treated with SRS had a longer OS than did those in the erlotinib group (median, 64 months; P=.004). The median time to intracranial progression was 17 months. There was a longer time to intracranial progression in patients who received WBRT than in those who received erlotinib upfront (median, 24 vs 16 months, P=.04). Patients in the erlotinib or SRS group were more likely to experience intracranial failure as a component of first failure, whereas WBRT patients were more likely to experience failure outside the brain (P=.004). Conclusions: The survival of patients with EGFR-mutant adenocarcinoma with BM is notably long, whether they receive upfront erlotinib or brain RT. We observed longer intracranial control with WBRT, even though the WBRT patients had a higher burden of intracranial disease. Despite the equivalent survival between the WBRT and erlotinib group, this study underscores the role of WBRT in producing durable intracranial control in comparison with a targeted biologic agent with known central nervous system activity.

  13. Metabolite signatures in hydrophilic extracts of mouse lungs exposed to cigarette smoke revealed by 1H NMR metabolomics investigation

    SciTech Connect (OSTI)

    Hu, Jian Z.; Wang, Xuan; Feng, Ju; Webb-Robertson, Bobbie-Jo M.; Waters, Katrina M.; Tilton, Susan C.; Pounds, Joel G.; Corley, Richard A.; Liu, Maili; Hu, Mary Y.

    2015-05-12

    Herein, 1H-NMR metabolomics are carried out to evaluate the changes of metabolites in lungs of mice exposed to cigarette smoke. It is found that the concentrations of adenosine derivatives (i.e. ATP, ADP and AMP), inosine and uridine are significantly fluctuated in the lungs of mice exposed to cigarette smoke compared with those of controls regardless the mouse is obese or regular weight. The decreased ATP, ADP, AMP and elevated inosine predict that the deaminases in charge of adenosine derivatives to inosine derivatives conversion are altered in lungs of mice exposed to cigarette smoke. Transcriptional analysis reveals that the concentrations of adenosine monophosphate deaminase and adenosine deaminase are different in the lungs of mice exposed to cigarette smoke, confirming the prediction from metabolomics studies. We also found, for the first time, that the ratio of glycerophosphocholine (GPC) to phosphocholine (PC) is significantly increased in the lungs of obese mice compared with regular weight mice. The ratio of GPC/PC is further elevated in the lungs of obese group by cigarette smoke exposure. Since GPC/PC ratio is a known biomarker for cancer, these results may suggest that obese group is more susceptible to lung cancer when exposed to cigarette smoke.

  14. Programs for Increasing the Engagement of Underrepresented Ethnic Groups and People with Disabilities in HPC. Final assessment report

    SciTech Connect (OSTI)

    Taylor, Valerie

    2012-12-23

    Given the significant impact of computing on society, it is important that all cultures, especially underrepresented cultures, are fully engaged in the field of computing to ensure that everyone benefits from the advances in computing. This proposal is focused on the field of high performance computing. The lack of cultural diversity in computing, in particular high performance computing, is especially evident with respect to the following ethnic groups African Americans, Hispanics, and Native Americans as well as People with Disabilities. The goal of this proposal is to organize and coordinate a National Laboratory Career Development Workshop focused on underrepresented cultures (ethnic cultures and disability cultures) in high performance computing. It is expected that the proposed workshop will increase the engagement of underrepresented cultures in HPC through increased exposure to the excellent work at the national laboratories. The National Laboratory Workshops are focused on the recruitment of senior graduate students and the retention of junior lab staff through the various panels and discussions at the workshop. Further, the workshop will include a community building component that extends beyond the workshop. The workshop was held was held at the Lawrence Livermore National Laboratory campus in Livermore, CA. from June 14 - 15, 2012. The grant provided funding for 25 participants from underrepresented groups. The workshop also included another 25 local participants in the summer programs at Lawrence Livermore National Laboratory. Below are some key results from the assessment of the workshops: 86% of the participants indicated strongly agree or agree to the statement "I am more likely to consider/continue a career at a national laboratory as a result of participating in this workshop." 77% indicated strongly agree or agree to the statement "I plan to pursue a summer internship at a national laboratory." 100% of the participants indicated strongly agree or agree to the statement "The CMD-IT NLPDEV workshop was a valuable experience."

  15. Experimental validation of the van Herk margin formula for lung radiation therapy

    SciTech Connect (OSTI)

    Ecclestone, Gillian; Heath, Emily; Bissonnette, Jean-Pierre

    2013-11-15

    Purpose: To validate the van Herk margin formula for lung radiation therapy using realistic dose calculation algorithms and respiratory motion modeling. The robustness of the margin formula against variations in lesion size, peak-to-peak motion amplitude, tissue density, treatment technique, and plan conformity was assessed, along with the margin formula assumption of a homogeneous dose distribution with perfect plan conformity.Methods: 3DCRT and IMRT lung treatment plans were generated within the ORBIT treatment planning platform (RaySearch Laboratories, Sweden) on 4DCT datasets of virtual phantoms. Random and systematic respiratory motion induced errors were simulated using deformable registration and dose accumulation tools available within ORBIT for simulated cases of varying lesion sizes, peak-to-peak motion amplitudes, tissue densities, and plan conformities. A detailed comparison between the margin formula dose profile model, the planned dose profiles, and penumbra widths was also conducted to test the assumptions of the margin formula. Finally, a correction to account for imperfect plan conformity was tested as well as a novel application of the margin formula that accounts for the patient-specific motion trajectory.Results: The van Herk margin formula ensured full clinical target volume coverage for all 3DCRT and IMRT plans of all conformities with the exception of small lesions in soft tissue. No dosimetric trends with respect to plan technique or lesion size were observed for the systematic and random error simulations. However, accumulated plans showed that plan conformity decreased with increasing tumor motion amplitude. When comparing dose profiles assumed in the margin formula model to the treatment plans, discrepancies in the low dose regions were observed for the random and systematic error simulations. However, the margin formula respected, in all experiments, the 95% dose coverage required for planning target volume (PTV) margin derivation, as defined by the ICRU; thus, suitable PTV margins were estimated. The penumbra widths calculated in lung tissue for each plan were found to be very similar to the 6.4 mm value assumed by the margin formula model. The plan conformity correction yielded inconsistent results which were largely affected by image and dose grid resolution while the trajectory modified PTV plans yielded a dosimetric benefit over the standard internal target volumes approach with up to a 5% decrease in the V20 value.Conclusions: The margin formula showed to be robust against variations in tumor size and motion, treatment technique, plan conformity, as well as low tissue density. This was validated by maintaining coverage of all of the derived PTVs by 95% dose level, as required by the formal definition of the PTV. However, the assumption of perfect plan conformity in the margin formula derivation yields conservative margin estimation. Future modifications to the margin formula will require a correction for plan conformity. Plan conformity can also be improved by using the proposed trajectory modified PTV planning approach. This proves especially beneficial for tumors with a large anteriorposterior component of respiratory motion.

  16. Influence of radiation therapy on the lung-tissue in breast cancer patients: CT-assessed density changes and associated symptoms

    SciTech Connect (OSTI)

    Rotstein, S.; Lax, I.; Svane, G. )

    1990-01-01

    The relative electron density of lung tissue was measured from computer tomography (CT) slices in 33 breast cancer patients treated by various techniques of adjuvant radiotherapy. The measurements were made before radiotherapy, 3 months and 9 months after completion of radiation therapy. The changes in lung densities at 3 months and 9 months were compared to radiation induced radiological (CT) findings. In addition, subjective symptoms such as cough and dyspnoea were assessed before and after radiotherapy. It was observed that the mean of the relative electron density of lung tissue varied from 0.25 when the whole lung was considered to 0.17 when only the anterior lateral quarter of the lung was taken into account. In patients with positive radiological (CT) findings the mean lung density of the anterior lateral quarter increased 2.1 times 3 months after radiotherapy and was still increased 1.6 times 6 months later. For those patients without findings, in the CT pictures the corresponding values were 1.2 and 1.1, respectively. The standard deviation of the pixel values within the anterior lateral quarter of the lung increased 3.8 times and 3.2 times at 3 months and 9 months, respectively, in the former group, as opposed to 1.2 and 1.1 in the latter group. Thirteen patients had an increase in either cough or dyspnoea as observed 3 months after completion of radiotherapy. In eleven patients these symptoms persisted 6 months later. No significant correlation was found between radiological findings and subjective symptoms. However, when three different treatment techniques were compared among 29 patients the highest rate of radiological findings was observed in patients in which the largest lung volumes received the target dose. A tendency towards an increased rate of subjective symptoms was also found in this group.

  17. Method of using 5,10,15,20-tetrakis(carboxyphenyl)porphine for detecting cancers of the lung

    DOE Patents [OSTI]

    Cole, Dean A. (60 San Juan St., Los Alamos, NM 87544); Moody, III, David C. (402 Pine Tree La., Boulder, CO 80304); Ellinwood, L. Edward (694 Sperber La., Grand Junction, CO 81506); Klein, M. Gerard (715 Victor Dr., Grand Junction, CO 81506)

    1992-01-01

    Method using tetra-aryl porphyrins for and, in particular, 5,10,15,20-tetrakis(4-carboxyphenyl)porphine as a fluorescent tracer for cancers of the lung, and as a radiotracer therefor as a complex with .sup.67 Cu. The latter complex also provides a source of beta radiation for selective destruction of lung malignancies as well as gamma radiation useful for image analysis of the situs thereof by single photon emission computed tomography, as an example, both in vivo. Copper-64 may be substituted for the .sup.67 Cu if only radiotracer characteristics are of interest. This lighter isotope of copper is a positron emitter, and positron emission tomography techniques cna be used to locate the malignant tissue mass.

  18. Method using 5,10,15,20-tetrakis(4-carboxyphenyl)porphine for treating cancers of the lung

    DOE Patents [OSTI]

    Cole, Dean A. (Germantown, MD); Moody, III, David C. (Superior, CO); Ellinwood, L. Edward (Grand Junction, CO); Klein, M. Gerard (Grand Junction, CO)

    1995-01-01

    Method using tetra-aryl porphyrins for and, in particular, 5,10,15,20-tetrakis(4-carboxyphenyl)porphine as a fluorescent tracer for cancers of the lung, and as a radiotracer therefor as a complex with .sup.67 Cu. The latter complex also provides a source of beta radiation for selective destruction of lung malignancies as well as gamma radiation useful for image analysis of the situs thereof by single photon emission computed tomography, as an example, both in vivo. Copper-64 may be substituted for the .sup.67 Cu if only radiotracer characteristics are of interest. This lighter isotope of copper is a positron emitter, and positron emission tomography techniques can be used to locate the malignant tissue mass.

  19. SU-F-BRF-12: Investigating Dosimetric Effects of Inter-Fraction Deformation in Lung Cancer Stereotactic Body Radiotherapy (SBRT)

    SciTech Connect (OSTI)

    Jia, J; Tian, Z; Gu, X; Yan, H; Jia, X; Jiang, S

    2014-06-15

    Purpose: We studied dosimetric effects of inter-fraction deformation in lung stereotactic body radiotherapy (SBRT), in order to investigate the necessity of adaptive re-planning for lung SBRT treatments. Methods: Six lung cancer patients with different treatment fractions were retrospectively investigated. All the patients were immobilized and localized with a stereotactic body frame and were treated under cone-beam CT (CBCT) image guidance at each fraction. We calculated the actual delivered dose of the treatment plan using the up-to-date patient geometry of each fraction, and compared the dose with the intended plan dose to investigate the dosimetric effects of the inter-fraction deformation. Deformable registration was carried out between the treatment planning CT and the CBCT of each fraction to obtain deformed planning CT for more accurate dose calculations of the delivered dose. The extent of the inter-fraction deformation was also evaluated by calculating the dice similarity coefficient between the delineated structures on the planning CT and those on the deformed planning CT. Results: The average dice coefficients for PTV, spinal cord, esophagus were 0.87, 0.83 and 0.69, respectively. The volume of PTV covered by prescription dose was decreased by 23.78% on average for all fractions and all patients. For spinal cord and esophagus, the volumes covered by the constraint dose were increased by 4.57% and 3.83%. The maximum dose was also increased by 4.11% for spinal cord and 4.29% for esophagus. Conclusion: Due to inter-fraction deformation, large deterioration was found in both PTV coverage and OAR sparing, which demonstrated the needs for adaptive re-planning of lung SBRT cases to improve target coverage while reducing radiation dose to nearby normal tissues.

  20. SciSat AM: Stereo 03: Dosmetric evaluation of single versus multi-arc VMAT for lung SBRT

    SciTech Connect (OSTI)

    Karan, T; Taremi, M; Comsa, D; Allibhai, Z; Ryan, M; Le, K

    2014-08-15

    Five non-small cell lung cancer patients previously treated with stereotactic body radiation therapy using the VMAT (volumetric modulated arc therapy) technique were selected for this retrospective study. Plans were re-optimized using Pinnacle treatment planning system (v9.0, Philips Medical), with the basis for comparison a two-arc plan involving a 360 arc in addition to a 90 arc with a couch kick. Additionally a single 360 arc was optimized for comparison, as well as a partial arc covering ?230, avoiding the contralateral lung. All plans met target coverage criteria as dictated by RTOG0236. Plans were evaluated based on conformity, sparing of organs at risk and practical considerations of delivery. Conformity was best in the two-arc plan; however the decrease seen in one- and partial arc plans was not statistically significant as tested by the Wilcoxon rank sum test. The partial-arc plan resulted in the lowest esophagus and trachea dose and the highest heart dose, however none of the plans exceeded organ at risk tolerances for lung SBRT. Partial arcs resulted in plans with slightly cooler dose distributions, a decrease in low dose spillage and an overall lower mean lung dose. The decrease in treatment time was on average 36 and 40 seconds for single and partial arcs, respectively, with partial arcs requiring the lowest number of MUs. The slight decrease in conformity seen in one-arc plans is offset by an increase in efficiency (optimization and treatment time, MUs) making the implementation of a single or partial-arc treatment technique clinically desirable.

  1. PR-Set7 is degraded in a conditional Cul4A transgenic mouse model of lung cancer

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Wang, Yang; Xu, Zhidong; Mao, Jian -Hua; Hsieh, David; Au, Alfred; Jablons, David M.; Li, Hui; You, Lian

    2015-06-01

    Background and objective. Maintenance of genomic integrity is essential to ensure normal organismal development and to prevent diseases such as cancer. PR-Set7 (also known as Set8) is a cell cycle regulated enzyme that catalyses monomethylation of histone 4 at Lys20 (H4K20me1) to promote chromosome condensation and prevent DNA damage. Recent studies show that CRL4CDT2-mediated ubiquitylation of PR-Set7 leads to its degradation during S phase and after DNA damage. This might occur to ensure appropriate changes in chromosome structure during the cell cycle or to preserve genome integrity after DNA damage. Methods. We developed a new model of lung tumor developmentmore » in mice harboring a conditionally expressed allele of Cul4A. We have therefore used a mouse model to demonstrate for the first time that Cul4A is oncogenic in vivo. With this model, staining of PR-Set7 in the preneoplastic and tumor lesions in AdenoCre-induced mouse lungs was performed. Meanwhile we identified higher protein level changes of γ-tubulin and pericentrin by IHC. Results. The level of PR-Set7 down-regulated in the preneoplastic and adenocarcinomous lesions following over-expression of Cul4A. We also identified higher levels of the proteins pericentrin and γ-tubulin in Cul4A mouse lungs induced by AdenoCre. Conclusion. PR-Set7 is a direct target of Cul4A for degradation and involved in the formation of lung tumors in the conditional Cul4A transgenic mouse model.« less

  2. Stereotactic Ablative Radiation Therapy as First Local Therapy for Lung Oligometastases From Colorectal Cancer: A Single-Institution Cohort Study

    SciTech Connect (OSTI)

    Filippi, Andrea Riccardo; Badellino, Serena; Ceccarelli, Manuela; Guarneri, Alessia; Franco, Pierfrancesco; Monagheddu, Chiara; Spadi, Rosella; Ragona, Riccardo; Racca, Patrizia; Ricardi, Umberto

    2015-03-01

    Purpose: To estimate stereotactic ablative radiation therapy (SABR) efficacy and its potential role as an alternative to surgery for the treatment of lung metastases from colorectal cancer. Methods and Materials: Forty consecutive patients who received SABR as first local therapy at the time of lung progression were included, from 2004 to 2014. The primary study endpoint was overall survival. Secondary endpoints were progression-free survival and safety. Results: A single nodule was treated in 26 patients (65%), 2 nodules in 10 patients (25%), 3 in 3 patients (7.5%), and 4 in 1 patient (2.5%), for a total of 59 lesions. The median delivered biological effective dose was 96 Gy, in 1 to 8 daily fractions. Median follow-up time was 20 months (range, 3-72 months). Overall survival rates at 1, 2, and 5 years were, respectively, 84%, 73%, and 39%, with 14 patients (35%) dead. Median overall survival was 46 months. Progression occurred in 25 patients (62.5%), at a median interval of 8 months; failure at SABR site was observed in 3 patients (7.5%). Progression-free survival rates were 49% and 27% at 1 and 2 years, respectively. Discussion: The results of this retrospective exploratory analysis suggest safety and efficacy of SABR in patients affected with colorectal cancer lung oligometastases and urge inclusion of SABR in prospective clinical trials.

  3. Zinc chromate induces chromosome instability and DNA double strand breaks in human lung cells

    SciTech Connect (OSTI)

    Xie Hong; Holmes, Amie L.; Young, Jamie L.; Qin Qin; Joyce, Kellie; Pelsue, Stephen C.; Peng Cheng; Wise, Sandra S.; Jeevarajan, Antony S.; Wallace, William T.; Hammond, Dianne; Wise, John Pierce E-mail: John.Wise@usm.maine.edu

    2009-02-01

    Hexavalent chromium Cr(VI) is a respiratory toxicant and carcinogen, with solubility playing an important role in its carcinogenic potential. Zinc chromate, a water insoluble or 'particulate' Cr(VI) compound, has been shown to be carcinogenic in epidemiology studies and to induce tumors in experimental animals, but its genotoxicity is poorly understood. Our study shows that zinc chromate induced concentration-dependent increases in cytotoxicity, chromosome damage and DNA double strand breaks in human lung cells. In response to zinc chromate-induced breaks, MRE11 expression was increased and ATM and ATR were phosphorylated, indicating that the DNA double strand break repair system was initiated in the cells. In addition, our data show that zinc chromate-induced double strand breaks were only observed in the G2/M phase population, with no significant amount of double strand breaks observed in G1 and S phase cells. These data will aid in understanding the mechanisms of zinc chromate toxicity and carcinogenesis.

  4. Designing Targets for Elective Nodal Irradiation in Lung Cancer Radiotherapy: A Planning Study

    SciTech Connect (OSTI)

    Kepka, Lucyna; Tatro, Daniel; Moran, Jean M.; Quint, Leslie E.; Hayman, James A.; Ten Haken, Randall K.; Kong Fengming

    2009-04-01

    Purpose: To assess doses received by mediastinal and hilar lymph node stations (LNS) delineated according to published recommendations when 'standard' two-dimensional (2D) elective fields are applied and to assess doses to critical structures when fields are designed using 2D and three-dimensional (3D) treatment planning for elective irradiation. Methods and Materials: LNS were delineated on axial CT scans according to existing recommendations. For each case and tumor location, 2D anteroposterior-posteroanterior (AP-PA) elective fields were applied using the AP-PA CT topograms. From the 2D portal fields, 3D dose distributions were then calculated to particular LNS. Next, 3D plans were prepared for elective nodal irradiation for tumors of different lobes. Doses for critical structures were compared for 2D and 3D plans. Results: LNS 1/2R, 1/2L, 3A, 3P, 5, 6, and 8 were not adequately covered in a substantial part of plans by standard 2D portals when guidelines for delineation were strictly followed. The magnitude of the lack of coverage increased with margin application. There was a trend for a higher yet probably still safe dose delivered to lung for 3D plans compared with 2D plans with a prescription dose of 45 Gy. Conclusions: 2D fields did not entirely cover LNS delineated according to the recommendations for 3D techniques. A strict adherence to these guidelines may lead to larger portals than traditionally constructed using 2D methods. Some modifications for clinical implementation are discussed.

  5. Impact of Neoadjuvant Radiation on Survival in Stage III Non-Small-Cell Lung Cancer

    SciTech Connect (OSTI)

    Koshy, Matthew, E-mail: mkoshy@umm.ed [Department of Radiation Oncology, University of Maryland School of Medicine and University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD (United States); Goloubeva, Olga; Suntharalingam, Mohan [Department of Radiation Oncology, University of Maryland School of Medicine and University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD (United States)

    2011-04-01

    Purpose: The role of surgery in Stage III non-small-cell lung cancer (NSCLC) is controversial. This study was undertaken to assess the impact of neoadjuvant radiation therapy for Stage III NSCLC. Methods and Materials: This was a retrospective study from the Surveillance, Epidemiology, and End Results (SEER) database that included patients who were 18 years and older with NSCLC classified as Stage III and who underwent definitive therapy from 1988 to 2004. Patients were characterized by type of treatment received. Survival functions were estimated by the Kaplan-Meier method, and Cox regression model was used to analyze trends in overall (OS) and cause-specific survival (CSS). Results: A total of 48,131 patients were selected, with a median follow-up of 10 months (range, 0-203 months). By type of treatment, the 3-year OS was 10% with radiation therapy (RT), 37% with surgery (S), 34% with surgery and postoperative radiation (S-RT), and 45% with neoadjuvant radiation followed by surgery (Neo-RT) (p = 0.0001). Multivariable Cox model identified sex, race, laterality, T stage, N stage, and type of treatment as factors affecting survival. Estimated hazard ratios (HR) adjusted for other variables in regression model showed the types of treatment: S (HR, 1.3; 95% confidence interval [CI], 1.2-1.4), S-RT (HR, 1.2; 95% CI, 1.1-1.3), and RT (HR, 2.3; 95% CI, 2.15-2.53) were associated with significantly worse overall survival when compared with Neo-RT (p = 0.0001). Conclusion: This population based study demonstrates that patients with Stage III NSCLC receiving Neo-RT had significantly improved overall survival when compared with other treatment groups.

  6. Prognostic Factors in Stereotactic Body Radiotherapy for Non-Small-Cell Lung Cancer

    SciTech Connect (OSTI)

    Matsuo, Yukinori, E-mail: ymatsuo@kuhp.kyoto-u.ac.j [Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Shibuya, Keiko [Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Nagata, Yasushi [Division of Radiation Oncology, Hiroshima University Hospital, Hiroshima (Japan); Takayama, Kenji; Norihisa, Yoshiki; Mizowaki, Takashi; Narabayashi, Masaru; Sakanaka, Katsuyuki; Hiraoka, Masahiro [Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto (Japan)

    2011-03-15

    Purpose: To investigate the factors that influence clinical outcomes after stereotactic body radiotherapy (SBRT) for non-small-cell lung cancer (NSCLC). Methods and Materials: A total of 101 consecutive patients who underwent SBRT with 48 Gy in 4 fractions for histologically confirmed Stage I NSCLC were enrolled in this study. Factors including age, maximal tumor diameter, sex, performance status, operability, histology, and overall treatment time were evaluated with regard to local progression (LP), disease progression (DP), and overall survival (OS) using the Cox proportional hazards model. Prognostic models were built with recursive partitioning analysis. Results: Three-year OS was 58.6% with a median follow-up of 31.4 months. Cumulative incidence rates of LP and DP were 13.2% and 40.8% at 3 years, respectively. Multivariate analysis demonstrated that tumor diameter was a significant factor in all endpoints of LP, DP, and OS. Other significant factors were age in DP and sex in OS. Recursive partitioning analysis indicated a condition for good prognosis (Class I) as follows: female or T1a (tumor diameter {<=}20 mm). When the remaining male patients with T1b-2a (>20 mm) were defined as Class II, 3-year LP, DP, and OS were 6.8%, 23.6%, and 69.9% in recursive partitioning analysis Class I, respectively, whereas these values were 19.9%, 58.3%, and 47.1% in Class II. The differences between the classes were statistically significant. Conclusions: Tumor diameter and sex were the most significant factors in SBRT for NSCLC. T1a or female patients had good prognosis.

  7. Rapid Disease Progression With Delay in Treatment of Non-Small-Cell Lung Cancer

    SciTech Connect (OSTI)

    Mohammed, Nasiruddin [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Kestin, Larry Llyn, E-mail: lkestin@beaumont.ed [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Grills, Inga Siiner; Battu, Madhu; Fitch, Dwight Lamar [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Wong, Ching-yee Oliver [Department of Nuclear Medicine, William Beaumont Hospital, Royal Oak, MI (United States); Margolis, Jeffrey Harold [Department of Medical Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Chmielewski, Gary William; Welsh, Robert James [Department of Thoracic Surgery, William Beaumont Hospital, Royal Oak, MI (United States)

    2011-02-01

    Purpose: To assess rate of disease progression from diagnosis to initiation of treatment for Stage I-IIIB non-small-cell lung cancer (NSCLC). Methods and Materials: Forty patients with NSCLC underwent at least two sets of computed tomography (CT) and 18-fluorodeoxyglucose positron emission tomography (PET) scans at various time intervals before treatment. Progression was defined as development of any new lymph node involvement, site of disease, or stage change. Results: Median time interval between first and second CT scans was 13.4 weeks, and between first and second PET scans was 9.0 weeks. Median initial primary maximum tumor dimension (MTD) was 3.5 cm (0.6-8.5 cm) with a median standardized uptake value (SUV) of 13.0 (1.7-38.5). The median MTD increased by a median of 1.0 cm (mean, 1.6 cm) between scans for a median relative MTD increase of 35% (mean, 59%). Nineteen patients (48%) progressed between scans. Rate of any progression was 13%, 31%, and 46% at 4, 8, and 16 weeks, respectively. Upstaging occurred in 3%, 13%, and 21% at these intervals. Distant metastasis became evident in 3%, 13%, and 13% after 4, 8, and 16 weeks, respectively. T and N stage were associated with progression, whereas histology, grade, sex, age, and maximum SUV were not. At 3 years, overall survival for Stage III patients with vs. without progression was 18% vs. 67%, p = 0.05. Conclusions: With NSCLC, treatment delay can lead to disease progression. Diagnosis, staging, and treatment initiation should be expedited. After 4-8 weeks of delay, complete restaging should be strongly considered.

  8. Tropical Forest Trust | Open Energy Information

    Open Energy Info (EERE)

    in Portland, Oregon. Overview "We focus on products and supply chains to bring about sustainable development. That's because we believe this is where the most concrete and powerful...

  9. Trust Anchor Fact Sheet.cdr

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    interface (HMI) system and a programmable logic controller (PLC) to validate that commands to the PLC originated from the HMI and were not injected in the communication stream. ...

  10. Westwind Trust Wind Farm | Open Energy Information

    Open Energy Info (EERE)

    Commercial Scale Wind Facility Status In Service Energy Purchaser Southern California Edison Co Location San Gorgonio CA Coordinates 33.9095, -116.734 Show Map Loading map......

  11. Advanced Credentialing for Trusted Networks - Energy Innovation...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Of equal concern, recent disasters have demonstrated that people are turning more to social media as opposed to traditional communication media for their information....

  12. Efficiency Maine Trust - Renewable Resource Fund | Department...

    Broader source: Energy.gov (indexed) [DOE]

    State Maine Program Type Public Benefits Fund Summary Maine's public benefits fund for renewable energy was established as part of the state's electric-industry restructuring...

  13. Ethanol metabolism, oxidative stress, and endoplasmic reticulum stress responses in the lungs of hepatic alcohol dehydrogenase deficient deer mice after chronic ethanol feeding

    SciTech Connect (OSTI)

    Kaphalia, Lata; Boroumand, Nahal; Hyunsu, Ju; Kaphalia, Bhupendra S.; Calhoun, William J.

    2014-06-01

    Consumption and over-consumption of alcoholic beverages are well-recognized contributors to a variety of pulmonary disorders, even in the absence of intoxication. The mechanisms by which alcohol (ethanol) may produce disease include oxidative stress and prolonged endoplasmic reticulum (ER) stress. Many aspects of these processes remain incompletely understood due to a lack of a suitable animal model. Chronic alcohol over-consumption reduces hepatic alcohol dehydrogenase (ADH), the principal canonical metabolic pathway of ethanol oxidation. We therefore modeled this situation using hepatic ADH-deficient deer mice fed 3.5% ethanol daily for 3 months. Blood ethanol concentration was 180 mg% in ethanol fed mice, compared to < 1.0% in the controls. Acetaldehyde (oxidative metabolite of ethanol) was minimally, but significantly increased in ethanol-fed vs. pair-fed control mice. Total fatty acid ethyl esters (FAEEs, nonoxidative metabolites of ethanol) were 47.6 ?g/g in the lungs of ethanol-fed mice as compared to 1.5 ?g/g in pair-fed controls. Histological and immunohistological evaluation showed perivascular and peribronchiolar lymphocytic infiltration, and significant oxidative injury, in the lungs of ethanol-fed mice compared to pair-fed controls. Several fold increases for cytochrome P450 2E1, caspase 8 and caspase 3 found in the lungs of ethanol-fed mice as compared to pair-fed controls suggest role of oxidative stress in ethanol-induced lung injury. ER stress and unfolded protein response signaling were also significantly increased in the lungs of ethanol-fed mice. Surprisingly, no significant activation of inositol-requiring enzyme-1? and spliced XBP1 was observed indicating a lack of activation of corrective mechanisms to reinstate ER homeostasis. The data suggest that oxidative stress and prolonged ER stress, coupled with formation and accumulation of cytotoxic FAEEs may contribute to the pathogenesis of alcoholic lung disease. - Highlights: Chronic ethanol feeding causes oxidative stress, ER stress and inflammation in lungs of ADH deer mice. Chronic ethanol feeding generates FAEEs (nonoxidative metabolites of ethanol) in lungs of ADH deer mice. Chronic ethanol feeding induces CYP2E1 in the lungs of ADH deer mice. Lack of ER homeostasis due to a prolonged ethanol feeding could trigger inflammation.

  14. SU-E-J-23: An Accurate Algorithm to Match Imperfectly Matched Images for Lung Tumor Detection Without Markers

    SciTech Connect (OSTI)

    Rozario, T; Bereg, S; Chiu, T; Liu, H; Kearney, V; Jiang, L; Mao, W

    2014-06-01

    Purpose: In order to locate lung tumors on projection images without internal markers, digitally reconstructed radiograph (DRR) is created and compared with projection images. Since lung tumors always move and their locations change on projection images while they are static on DRRs, a special DRR (background DRR) is generated based on modified anatomy from which lung tumors are removed. In addition, global discrepancies exist between DRRs and projections due to their different image originations, scattering, and noises. This adversely affects comparison accuracy. A simple but efficient comparison algorithm is reported. Methods: This method divides global images into a matrix of small tiles and similarities will be evaluated by calculating normalized cross correlation (NCC) between corresponding tiles on projections and DRRs. The tile configuration (tile locations) will be automatically optimized to keep the tumor within a single tile which has bad matching with the corresponding DRR tile. A pixel based linear transformation will be determined by linear interpolations of tile transformation results obtained during tile matching. The DRR will be transformed to the projection image level and subtracted from it. The resulting subtracted image now contains only the tumor. A DRR of the tumor is registered to the subtracted image to locate the tumor. Results: This method has been successfully applied to kV fluoro images (about 1000 images) acquired on a Vero (Brainlab) for dynamic tumor tracking on phantom studies. Radiation opaque markers are implanted and used as ground truth for tumor positions. Although, other organs and bony structures introduce strong signals superimposed on tumors at some angles, this method accurately locates tumors on every projection over 12 gantry angles. The maximum error is less than 2.6 mm while the total average error is 1.0 mm. Conclusion: This algorithm is capable of detecting tumor without markers despite strong background signals.

  15. SU-E-J-52: Dosimetric Benefit of Adaptive Re-Planning in Lung Cancer Stereotactic Body Radiotherapy (SBRT)

    SciTech Connect (OSTI)

    Jia, J; Tian, Z; Gu, X; Yan, H; Jiang, S; Jia, X

    2014-06-01

    Purpose: To investigate the dosimetric benefit of adaptive re-planning for lung stereotactic body radiotherapy(SBRT). Methods: Five lung cancer patients with SBRT treatment were retrospectively investigated. Our in-house supercomputing online re-planning environment (SCORE) was used to realize the re-planning process. First a deformable image registration was carried out to transfer contours from treatment planning CT to each treatment CBCT. Then an automatic re-planning using original plan DVH guided fluence-map optimization is performed to get a new plan for the up-to-date patient geometry. We compared the re-optimized plan to the original plan projected on the up-to-date patient geometry in critical dosimetric parameters, such as PTV coverage, spinal cord maximum and volumetric constraint dose, esophagus maximum and volumetric constraint dose. Results: The average volume of PTV covered by prescription dose for all patients was improved by 7.56% after the adaptive re-planning. The volume of the spinal cord receiving 14.5Gy and 23Gy (V14.5, V23) decreased by 1.48% and 0.68%, respectively. For the esophagus, the volume receiving 19.5Gy (V19.5) reduced by 1.37%. Meanwhile, the maximum dose dropped off by 2.87% for spinal cord and 4.80% for esophagus. Conclusion: Our experimental results demonstrate that adaptive re-planning for lung SBRT has the potential to minimize the dosimetric effect of inter-fraction deformation and thus improve target coverage while reducing the risk of toxicity to nearby normal tissues.

  16. SU-E-I-25: Determining Tube Current, Tube Voltage and Pitch Suitable for Low- Dose Lung Screening CT

    SciTech Connect (OSTI)

    Williams, K; Matthews, K

    2014-06-01

    Purpose: The quality of a computed tomography (CT) image and the dose delivered during its acquisition depend upon the acquisition parameters used. Tube current, tube voltage, and pitch are acquisition parameters that potentially affect image quality and dose. This study investigated physicians' abilities to characterize small, solid nodules in low-dose CT images for combinations of current, voltage and pitch, for three CT scanner models. Methods: Lung CT images was acquired of a Data Spectrum anthropomorphic torso phantom with various combinations of pitch, tube current, and tube voltage; this phantom was used because acrylic beads of various sizes could be placed within the lung compartments to simulate nodules. The phantom was imaged on two 16-slice scanners and a 64-slice scanner. The acquisition parameters spanned a range of estimated CTDI levels; the CTDI estimates from the acquisition software were verified by measurement. Several experienced radiologists viewed the phantom lung CT images and noted nodule location, size and shape, as well as the acceptability of overall image quality. Results: Image quality for assessment of nodules was deemed unsatisfactory for all scanners at 80 kV (any tube current) and at 35 mA (any tube voltage). Tube current of 50 mA or more at 120 kV resulted in similar assessments from all three scanners. Physician-measured sphere diameters were closer to actual diameters for larger spheres, higher tube current, and higher kV. Pitch influenced size measurements less for larger spheres than for smaller spheres. CTDI was typically overestimated by the scanner software compared to measurement. Conclusion: Based on this survey of acquisition parameters, a low-dose CT protocol of 120 kV, 50 mA, and pitch of 1.4 is recommended to balance patient dose and acceptable image quality. For three models of scanners, this protocol resulted in estimated CTDIs from 2.93.6 mGy.

  17. Respiration-Correlated Image Guidance Is the Most Important Radiotherapy Motion Management Strategy for Most Lung Cancer Patients

    SciTech Connect (OSTI)

    Korreman, Stine, E-mail: korreman@ruc.dk [Department of Science, Systems and Models, Roskilde University, Roskilde (Denmark); Department of Radiation Oncology, The Finsen Centre, Rigshospitalet, Copenhagen (Denmark); Niels Bohr Institute, University of Copenhagen, Copenhagen (Denmark); Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison (United States); Persson, Gitte; Nygaard, Ditte [Department of Radiation Oncology, The Finsen Centre, Rigshospitalet, Copenhagen (Denmark); Brink, Carsten [Laboratory of Radiation Physics, Odense University Hospital, Odense (Denmark); Faculty of Health Sciences, University of Southern Denmark, Odense (Denmark); Juhler-Nottrup, Trine [Department of Oncology, Herlev Hospital, Copenhagen (Denmark)

    2012-07-15

    Purpose: The purpose of this study was to quantify the effects of four-dimensional computed tomography (4DCT), 4D image guidance (4D-IG), and beam gating on calculated treatment field margins in a lung cancer patient population. Materials and Methods: Images were acquired from 46 lung cancer patients participating in four separate protocols at three institutions in Europe and the United States. Seven patients were imaged using fluoroscopy, and 39 patients were imaged using 4DCT. The magnitude of respiratory tumor motion was measured. The required treatment field margins were calculated using a statistical recipe (van Herk M, et al. Int J Radiat Oncol Biol Phys 2000;474:1121-1135), with magnitudes of all uncertainties, except respiratory peak-to-peak displacement, the same for all patients, taken from literature. Required margins for respiratory motion management were calculated using the residual respiratory tumor motion for each patient for various motion management strategies. Margin reductions for respiration management were calculated using 4DCT, 4D-IG, and gated beam delivery. Results: The median tumor motion magnitude was 4.4 mm for the 46 patients (range 0-29.3 mm). This value corresponded to required treatment field margins of 13.7 to 36.3 mm (median 14.4 mm). The use of 4DCT, 4D-IG, and beam gating required margins that were reduced by 0 to 13.9 mm (median 0.5 mm), 3 to 5.2 mm (median 5.1 mm), and 0 to 7 mm (median 0.2 mm), respectively, to a total of 8.5 to 12.4 mm (median 8.6 mm). Conclusion: A respiratory management strategy for lung cancer radiotherapy including planning on 4DCT scans and daily image guidance provides a potential reduction of 37% to 47% in treatment field margins. The 4D image guidance strategy was the most effective strategy for >85% of the patients.

  18. Phase 1 Study of Dose Escalation in Hypofractionated Proton Beam Therapy for Non-Small Cell Lung Cancer

    SciTech Connect (OSTI)

    Gomez, Daniel R., E-mail: dgomez@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gillin, Michael [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liao, Zhongxing [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wei, Caimiao [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lin, Steven H.; Swanick, Cameron; Alvarado, Tina; Komaki, Ritsuko; Cox, James D.; Chang, Joe Y. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-07-15

    Background: Many patients with locally advanced non-small cell lung cancer (NSCLC) cannot undergo concurrent chemotherapy because of comorbidities or poor performance status. Hypofractionated radiation regimens, if tolerable, may provide an option to these patients for effective local control. Methods and Materials: Twenty-five patients were enrolled in a phase 1 dose-escalation trial of proton beam therapy (PBT) from September 2010 through July 2012. Eligible patients had histologically documented lung cancer, thymic tumors, carcinoid tumors, or metastatic thyroid tumors. Concurrent chemotherapy was not allowed, but concurrent treatment with biologic agents was. The dose-escalation schema comprised 15 fractions of 3 Gy(relative biological effectiveness [RBE])/fraction, 3.5 Gy(RBE)/fraction, or 4 Gy(RBE)/fraction. Dose constraints were derived from biologically equivalent doses of standard fractionated treatment. Results: The median follow-up time for patients alive at the time of analysis was 13 months (range, 8-28 months). Fifteen patients received treatment to hilar or mediastinal lymph nodes. Two patients experienced dose-limiting toxicity possibly related to treatment; 1 received 3.5-Gy(RBE) fractions and experienced an in-field tracheoesophageal fistula 9 months after PBT and 1 month after bevacizumab. The other patient received 4-Gy(RBE) fractions and was hospitalized for bacterial pneumonia/radiation pneumonitis 4 months after PBT. Conclusion: Hypofractionated PBT to the thorax delivered over 3 weeks was well tolerated even with significant doses to the lungs and mediastinal structures. Phase 2/3 trials are needed to compare the efficacy of this technique with standard treatment for locally advanced NSCLC.

  19. Assessment of interpatient heterogeneity in tumor radiosensitivity for nonsmall cell lung cancer using tumor-volume variation data

    SciTech Connect (OSTI)

    Chvetsov, Alexei V. Schwartz, Jeffrey L.; Mayr, Nina; Yartsev, Slav

    2014-06-15

    Purpose: In our previous work, the authors showed that a distribution of cell surviving fractionsS{sub 2} in a heterogeneous group of patients could be derived from tumor-volume variation curves during radiotherapy for head and neck cancer. In this research study, the authors show that this algorithm can be applied to other tumors, specifically in nonsmall cell lung cancer. This new application includes larger patient volumes and includes comparison of data sets obtained at independent institutions. Methods: Our analysis was based on two data sets of tumor-volume variation curves for heterogeneous groups of 17 patients treated for nonsmall cell lung cancer with conventional dose fractionation. The data sets were obtained previously at two independent institutions by using megavoltage computed tomography. Statistical distributions of cell surviving fractionsS{sub 2} and clearance half-lives of lethally damaged cells T{sub 1/2} have been reconstructed in each patient group by using a version of the two-level cell population model of tumor response and a simulated annealing algorithm. The reconstructed statistical distributions of the cell surviving fractions have been compared to the distributions measured using predictive assays in vitro. Results: Nonsmall cell lung cancer presents certain difficulties for modeling surviving fractions using tumor-volume variation curves because of relatively large fractional hypoxic volume, low gradient of tumor-volume response, and possible uncertainties due to breathing motion. Despite these difficulties, cell surviving fractionsS{sub 2} for nonsmall cell lung cancer derived from tumor-volume variation measured at different institutions have similar probability density functions (PDFs) with mean values of 0.30 and 0.43 and standard deviations of 0.13 and 0.18, respectively. The PDFs for cell surviving fractions S{sub 2} reconstructed from tumor volume variation agree with the PDF measured in vitro. Conclusions: The data obtained in this work, when taken together with the data obtained previously for head and neck cancer, suggests that the cell surviving fractionsS{sub 2} can be reconstructed from the tumor volume variation curves measured during radiotherapy with conventional fractionation. The proposed method can be used for treatment evaluation and adaptation.

  20. Viscoelastic Model for Lung Parenchyma for Multi-Scale Modeling of Respiratory System Phase I: Hypo-Elastic Model for CFD Implementation

    SciTech Connect (OSTI)

    Freed, Alan D.; Einstein, Daniel R.

    2011-04-14

    An isotropic constitutive model for the parenchyma of lung has been derived from the theory of hypo-elasticity. The intent is to use it to represent the mechanical response of this soft tissue in sophisticated, computational, fluid-dynamic models of the lung. This demands that the continuum model be accurate, yet simple and effcient. An objective algorithm for its numeric integration is provided. The response of the model is determined for several boundary-value problems whose experiments are used for material characterization. The effective elastic, bulk, and shear moduli, and Poissons ratio, as tangent functions, are also derived. The model is characterized against published experimental data for lung. A bridge between this continuum model and a dodecahedral model of alveolar geometry is investigated, with preliminary findings being reported.

  1. Expression of transforming growth factor alpha in plutonium-239-induced lung neoplasms in dogs: investigations of autocrine mechanisms of growth

    SciTech Connect (OSTI)

    Gillett, N.A.; Stegelmeier, B.L.; Chang, I.Y.; Kelly, G. )

    1991-06-01

    We have previously shown that 47% of radiation-induced lung neoplasms in dogs exhibit increased expression of epidermal growth factor receptor (EGFR). In this study, we investigated the expression of transforming growth factor alpha (TGF-alpha), a ligand for EGFR, to determine if an autocrine mechanism for growth stimulation was present in these tumors. As determined by immunohistochemistry, 59% (26/44) of the lung neoplasms examined had increased expression of TGF-alpha. Expression of TGF-alpha was not related to the etiology of the tumor, e.g., spontaneous or plutonium-induced; however, it was related to the phenotype of the tumor. Statistical analysis of the correlation of EGFR and TGF-alpha expression within the same tumor did not show a positive association; however, specific phenotypes did have statistically significant expression of EGFR or TGF-alpha, suggesting that overexpression of either the ligand or its receptor conferred a growth advantage to the neoplasm. Twenty-seven percent (32/117) of radiation-induced proliferative epithelial foci expressed TGF-alpha, and a portion of those foci (8/32) expressed both EGFR and TGF-alpha. This supports the hypothesis that these foci represent preneoplastic lesions, and suggests that those foci exhibiting increased expression of the growth factor or its receptor are at greater risk for progressing to neoplasia.

  2. Understanding the chemical properties of macerals and minerals in coal and its potential application for occupational lung disease prevention

    SciTech Connect (OSTI)

    Huang, X.; Finkelman, R.B.

    2008-07-01

    The objective of this review was to assess whether some chemical parameters in coal play a role in producing environmental health problems. Basic properties of coal - such as chemical forms of the organic materials, structure, compositions of minerals - vary from one coal mine region to another as well as from coals of different ranks. Most importantly, changes in chemical properties of coals due to exposure to air and humidity after mining - a dynamic process - significantly affect toxicity attributed to coal and environmental fate. Although coal is an extremely complex and heterogeneous material, the fundamental properties of coal responsible for environmental and adverse health problems are probably related to the same inducing components of coal. For instance, oxidation of pyrite (FeS{sub 2}) in the coal forms iron sulfate and sulfuric acid, which produces occupational lung diseases (e.g., pneumoconiosis) and other environmental problems (e.g., acid mine drainage and acid rain). Calcite (CaCO{sub 3}) contained in certain coals alters the end products of pyrite oxidation, which may make these coals less toxic to human inhalation and less hazardous to environmental pollution. Finally, knowledge gained on understanding of the chemical properties of coals is illustrated to apply for prediction of toxicity due to coal possibly before large-scale mining and prevention of occupational lung disease during mining.

  3. Development of a Rhesus Monkey Lung Geometry Model and Application to Particle Deposition in Comparison to Humans

    SciTech Connect (OSTI)

    Asgharian, Bahman; Price, Owen; McClellan, Gene; Corley, Richard A.; Einstein, Daniel R.; Jacob, Rick E.; Harkema, Jack R.; Carey, Stephen A.; Schelegle, Edward; Hyde, D.; Kimbell, Julia; Miller, Frederick J.

    2012-11-01

    The exposure-dose-response characterization of an inhalation hazard established in an animal species needs to be translated to an equivalent characterization in humans relative to comparable doses or exposure scenarios. Here, the first geometry model of the conducting airways for rhesus monkeys is developed based upon CT images of the conducting airways of a 6-month-old male, rhesus monkey. An algorithm was developed for adding the alveolar region airways using published rhesus morphometric data. The resultant lung geometry model can be used in mechanistic particle or gaseous dosimetry models. Such dosimetry models require estimates of the upper respiratory tract volume of the animal and the functional residual capacity, as well as of the tidal volume and breathing frequency of the animal. The relationship of these variables to rhesus monkeys of differing body weights was established by synthesizing and modeling published data as well as modeling pulmonary function measurements on 121 rhesus control animals. Deposition patterns of particles up to 10 ?m in size were examined for endotracheal and and up to 5 ?m for spontaneous breathing in infant and young adult monkeys and compared to those for humans. Deposition fraction of respirable size particles was found to be higher in the conducting airways of infant and young adult rhesus monkeys compared to humans. Due to the filtering effect of the conducting airways, pulmonary deposition in rhesus monkeys was lower than that in humans. Future research areas are identified that would either allow replacing assumptions or improving the newly developed lung model.

  4. CT reconstruction techniques for improved accuracy of lung CT airway measurement

    SciTech Connect (OSTI)

    Rodriguez, A.; Ranallo, F. N.; Judy, P. F.; Gierada, D. S.; Fain, S. B.

    2014-11-01

    Purpose: To determine the impact of constrained reconstruction techniques on quantitative CT (qCT) of the lung parenchyma and airways for low x-ray radiation dose. Methods: Measurement of small airways with qCT remains a challenge, especially for low x-ray dose protocols. Images of the COPDGene quality assurance phantom (CTP698, The Phantom Laboratory, Salem, NY) were obtained using a GE discovery CT750 HD scanner for helical scans at x-ray radiation dose-equivalents ranging from 1 to 4.12 mSv (12100 mA s currenttime product). Other parameters were 40 mm collimation, 0.984 pitch, 0.5 s rotation, and 0.625 mm thickness. The phantom was sandwiched between 7.5 cm thick water attenuating phantoms for a total length of 20 cm to better simulate the scatter conditions of patient scans. Image data sets were reconstructed using STANDARD (STD), DETAIL, BONE, and EDGE algorithms for filtered back projection (FBP), 100% adaptive statistical iterative reconstruction (ASIR), and Veo reconstructions. Reduced (half) display field of view (DFOV) was used to increase sampling across airway phantom structures. Inner diameter (ID), wall area percent (WA%), and wall thickness (WT) measurements of eight airway mimicking tubes in the phantom, including a 2.5 mm ID (42.6 WA%, 0.4 mm WT), 3 mm ID (49.0 WA%, 0.6 mm WT), and 6 mm ID (49.0 WA%, 1.2 mm WT) were performed with Airway Inspector (Surgical Planning Laboratory, Brigham and Womens Hospital, Boston, MA) using the phase congruency edge detection method. The average of individual measures at five central slices of the phantom was taken to reduce measurement error. Results: WA% measures were greatly overestimated while IDs were underestimated for the smaller airways, especially for reconstructions at full DFOV (36 cm) using the STD kernel, due to poor sampling and spatial resolution (0.7 mm pixel size). Despite low radiation dose, the ID of the 6 mm ID airway was consistently measured accurately for all methods other than STD FBP. Veo reconstructions showed slight improvement over STD FBP reconstructions (4%9% increase in accuracy). The most improved ID and WA% measures were for the smaller airways, especially for low dose scans reconstructed at half DFOV (18 cm) with the EDGE algorithm in combination with 100% ASIR to mitigate noise. Using the BONE + ASIR at half BONE technique, measures improved by a factor of 2 over STD FBP even at a quarter of the x-ray dose. Conclusions: The flexibility of ASIR in combination with higher frequency algorithms, such as BONE, provided the greatest accuracy for conventional and low x-ray dose relative to FBP. Veo provided more modest improvement in qCT measures, likely due to its compatibility only with the smoother STD kernel.

  5. Survival and Quality of Life After Stereotactic or 3D-Conformal Radiotherapy for Inoperable Early-Stage Lung Cancer

    SciTech Connect (OSTI)

    Widder, Joachim; Postmus, Douwe; Ubbels, Jan F.; Wiegman, Erwin M.; Langendijk, Johannes A.

    2011-11-15

    Purpose: To investigate survival and local recurrence after stereotactic ablative radiotherapy (SABR) or three-dimensional conformal radiotherapy (3D-CRT) administered for early-stage primary lung cancer and to investigate longitudinal changes of health-related quality of life (HRQOL) parameters after either treatment. Methods and Materials: Two prospective cohorts of inoperable patients with T1-2N0M0 primary lung tumors were analyzed. Patients received 70 Gy in 35 fractions with 3D-CRT or 60 Gy in three to eight fractions with SABR. Global quality of life (GQOL), physical functioning (PF), and patient-rated dyspnea were assessed using the respective dimensions of European Organization for Research and Treatment of Cancer Core Questionnaire-C30 and LC13. HRQOL was analyzed using multivariate linear mixed-effects modeling, survival and local control (LC) using the Kaplan-Meier method, Cox proportional hazards analysis, and Fine and Gray multivariate competing risk analysis as appropriate. Results: Overall survival (OS) was better after SABR compared with 3D-CRT with a HR of 2.6 (95% confidence interval [CI]: 1.5-4.8; p < 0.01). 3D-CRT conferred a subhazard ratio for LC of 5.0 (95% CI: 1.7-14.7; p < 0.01) compared with SABR. GQOL and PF were stable after SABR (p = 0.21 and p = 0.62, respectively). Dyspnea increased after SABR by 3.2 out of 100 points (95% CI: 1.0-5.3; p < 0.01), which is clinically insignificant. At 1 year, PF decreased by an excess of 8.7 out of 100 points (95% CI: 2.8-14.7; p < 0.01) after 3D-CRT compared with SABR. Conclusion: In this nonrandomized comparison of two prospective cohorts of medically inoperable patients with Stage I lung cancer, OS and LC were better after SABR. GQOL, PF, and patient-rated dyspnea were stable after SABR, whereas PF decreased after 3D-CRT approaching clinical significance already at 1 year.

  6. Use of 4-Dimensional Computed Tomography-Based Ventilation Imaging to Correlate Lung Dose and Function With Clinical Outcomes

    SciTech Connect (OSTI)

    Vinogradskiy, Yevgeniy, E-mail: yevgeniy.vinogradskiy@ucdenver.edu [Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado (United States)] [Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado (United States); Castillo, Richard [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Castillo, Edward [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States) [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Computational and Applied Mathematics, Rice University, Houston, Texas (United States); Tucker, Susan L. [Departments of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Departments of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liao, Zhongxing [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Guerrero, Thomas [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States) [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Computational and Applied Mathematics, Rice University, Houston, Texas (United States); Martel, Mary K. [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-06-01

    Purpose: Four-dimensional computed tomography (4DCT)-based ventilation is an emerging imaging modality that can be used in the thoracic treatment planning process. The clinical benefit of using ventilation images in radiation treatment plans remains to be tested. The purpose of the current work was to test the potential benefit of using ventilation in treatment planning by evaluating whether dose to highly ventilated regions of the lung resulted in increased incidence of clinical toxicity. Methods and Materials: Pretreatment 4DCT data were used to compute pretreatment ventilation images for 96 lung cancer patients. Ventilation images were calculated using 4DCT data, deformable image registration, and a density-change based algorithm. Dosevolume and ventilation-based dose function metrics were computed for each patient. The ability of the dosevolume and ventilation-based dosefunction metrics to predict for severe (grade 3+) radiation pneumonitis was assessed using logistic regression analysis, area under the curve (AUC) metrics, and bootstrap methods. Results: A specific patient example is presented that demonstrates how incorporating ventilation-based functional information can help separate patients with and without toxicity. The logistic regression significance values were all lower for the dosefunction metrics (range P=.093-.250) than for their dosevolume equivalents (range, P=.331-.580). The AUC values were all greater for the dosefunction metrics (range, 0.569-0.620) than for their dosevolume equivalents (range, 0.500-0.544). Bootstrap results revealed an improvement in model fit using dosefunction metrics compared to dosevolume metrics that approached significance (range, P=.118-.155). Conclusions: To our knowledge, this is the first study that attempts to correlate lung dose and 4DCT ventilation-based function to thoracic toxicity after radiation therapy. Although the results were not significant at the .05 level, our data suggests that incorporating ventilation-based functional imaging can improve prediction for radiation pneumonitis. We present an important first step toward validating the use of 4DCT-based ventilation imaging in thoracic treatment planning.

  7. Association Between White Blood Cell Count Following Radiation Therapy With Radiation Pneumonitis in Non-Small Cell Lung Cancer

    SciTech Connect (OSTI)

    Tang, Chad; Gomez, Daniel R. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wang, Hongmei [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou (China); Levy, Lawrence B. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Zhuang, Yan [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Xu, Ting; Nguyen, Quynh; Komaki, Ritsuko [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liao, Zhongxing, E-mail: zliao@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2014-02-01

    Purpose: Radiation pneumonitis (RP) is an inflammatory response to radiation therapy (RT). We assessed the association between RP and white blood cell (WBC) count, an established metric of systemic inflammation, after RT for non-small cell lung cancer. Methods and Materials: We retrospectively analyzed 366 patients with non-small cell lung cancer who received ?60 Gy as definitive therapy. The primary endpoint was whether WBC count after RT (defined as 2 weeks through 3 months after RT completion) was associated with grade ?3 or grade ?2 RP. Median lung volume receiving ?20 Gy (V{sub 20}) was 31%, and post-RT WBC counts ranged from 1.7 to 21.2 10{sup 3} WBCs/?L. Odds ratios (ORs) associating clinical variables and post-RT WBC counts with RP were calculated via logistic regression. A recursive-partitioning algorithm was used to define optimal post-RT WBC count cut points. Results: Post-RT WBC counts were significantly higher in patients with grade ?3 RP than without (P<.05). Optimal cut points for post-RT WBC count were found to be 7.4 and 8.0 10{sup 3}/?L for grade ?3 and ?2 RP, respectively. Univariate analysis revealed significant associations between post-RT WBC count and grade ?3 (n=46, OR=2.6, 95% confidence interval [CI] 1.4?4.9, P=.003) and grade ?2 RP (n=164, OR=2.0, 95% CI 1.2?3.4, P=.01). This association held in a stepwise multivariate regression. Of note, V{sub 20} was found to be significantly associated with grade ?2 RP (OR=2.2, 95% CI 1.2?3.4, P=.01) and trended toward significance for grade ?3 RP (OR=1.9, 95% CI 1.0-3.5, P=.06). Conclusions: Post-RT WBC counts were significantly and independently associated with RP and have potential utility as a diagnostic or predictive marker for this toxicity.

  8. A CAD system for nodule detection in low-dose lung CTs based on region growing and a new active contour model

    SciTech Connect (OSTI)

    Bellotti, R.; De Carlo, F.; Gargano, G.; Tangaro, S.; Cascio, D.; Catanzariti, E.; Cerello, P.; Cheran, S. C.; Delogu, P.; De Mitri, I.; Fulcheri, C.; Grosso, D.; Retico, A.; Squarcia, S.; Tommasi, E.; Golosio, Bruno

    2007-12-15

    A computer-aided detection (CAD) system for the selection of lung nodules in computer tomography (CT) images is presented. The system is based on region growing (RG) algorithms and a new active contour model (ACM), implementing a local convex hull, able to draw the correct contour of the lung parenchyma and to include the pleural nodules. The CAD consists of three steps: (1) the lung parenchymal volume is segmented by means of a RG algorithm; the pleural nodules are included through the new ACM technique; (2) a RG algorithm is iteratively applied to the previously segmented volume in order to detect the candidate nodules; (3) a double-threshold cut and a neural network are applied to reduce the false positives (FPs). After having set the parameters on a clinical CT, the system works on whole scans, without the need for any manual selection. The CT database was recorded at the Pisa center of the ITALUNG-CT trial, the first Italian randomized controlled trial for the screening of the lung cancer. The detection rate of the system is 88.5% with 6.6 FPs/CT on 15 CT scans (about 4700 sectional images) with 26 nodules: 15 internal and 11 pleural. A reduction to 2.47 FPs/CT is achieved at 80% efficiency.

  9. Effects of two Asian sand dusts transported from the dust source regions of Inner Mongolia and northeast China on murine lung eosinophilia

    SciTech Connect (OSTI)

    He, Miao; Ichinose, Takamichi; Song, Yuan; Yoshida, Yasuhiro; Arashidani, Keiichi; Yoshida, Seiichi; Liu, Boying; Nishikawa, Masataka; Takano, Hirohisa; and others

    2013-11-01

    The quality and quantity of toxic materials adsorbed onto Asian sand dust (ASD) are different based on dust source regions and passage routes. The aggravating effects of two ASDs (ASD1 and ASD2) transported from the source regions of Inner Mongolia and northeast China on lung eosinophilia were compared to clarify the role of toxic materials in ASD. The ASDs contained different amounts of lipopolysaccharides (LPS) and ?-glucan (ASD1 < ASD2) and SiO{sub 2} (ASD1 > ASD2). CD-1 mice were instilled intratracheally with ASD1, ASD2 and/or ovalbumin (OVA) four times at 2-week intervals. ASD1 and ASD2 enhanced eosinophil recruitment induced by OVA in the submucosa of the airway, with goblet cell proliferation in the bronchial epithelium. ASD1 and ASD2 synergistically increased OVA-induced eosinophil-relevant cytokines interleukin-5 (IL-5), IL-13 (ASD1 < ASD2) and chemokine eotaxin (ASD1 > ASD2) in bronchoalveolar lavage fluid. ASD2 aggravating effects on lung eosinophilia were greater than ASD1. The role of LPS and ?-glucan in ASD2 on the production of pro-inflammatory mediators was assessed using in vitro bone marrow-derived macrophages (BMDMs) from wild type, Toll-like receptor 2-deficient (TLR2 ?/?), TLR4 ?/?, and MyD88 ?/? mice (on Balb/c background). ASD2-stimulated TLR2 ?/? BMDMs enhanced IL-6, IL-12, TNF-?, MCP-1 and MIP-1? secretion compared with ASD2-stimulated TLR4 ?/? BMDMs. Protein expression from ASD2-stimulated MyD88 ?/? BMDM were very low or undetectable. The in vitro results indicate that lung eosinophilia caused by ASD is TLR4 dependent. Therefore, the aggravation of OVA-related lung eosinophilia by ASD may be dependent on toxic substances derived from microbes, such as LPS, rather than SiO{sub 2}. - Highlights: Asian sand dust (ASD) from the deserts of China causes serious respiratory problems. The aggravating effects of two ASDs on lung eosinophilia were compared. The ASDs contained different LPS and ?-glucan (ASD1 < ASD2) and SiO{sub 2} (ASD1 > ASD2). The ASD2 aggravating effects on lung eosinophilia were greater than ASD1. The aggravation of lung eosinophilia may be dependent on LPS in ASD, rather than SiO{sub 2}.

  10. Epithelialmesenchymal transition during oncogenic transformation induced by hexavalent chromium involves reactive oxygen species-dependent mechanism in lung epithelial cells

    SciTech Connect (OSTI)

    Ding, Song-Ze; Yang, Yu-Xiu; Li, Xiu-Ling; Michelli-Rivera, Audrey; Han, Shuang-Yin; Wang, Lei; Pratheeshkumar, Poyil; Wang, Xin; Lu, Jian; Yin, Yuan-Qin; Budhraja, Amit; Hitron, Andrew J.

    2013-05-15

    Hexavalent chromium [Cr(VI)] is an important human carcinogen associated with pulmonary diseases and lung cancer. Exposure to Cr(VI) induces DNA damage, cell morphological change and malignant transformation in human lung epithelial cells. Despite extensive studies, the molecular mechanisms remain elusive, it is also not known if Cr(VI)-induced transformation might accompany with invasive properties to facilitate metastasis. We aimed to study Cr(VI)-induced epithelialmesenchymal transition (EMT) and invasion during oncogenic transformation in lung epithelial cells. The results showed that Cr(VI) at low doses represses E-cadherin mRNA and protein expression, enhances mesenchymal marker vimentin expression and transforms the epithelial cell into fibroblastoid morphology. Cr(VI) also increases cell invasion and promotes colony formation. Further studies indicated that Cr(VI) uses multiple mechanisms to repress E-cadherin expression, including activation of E-cadherin repressors such as Slug, ZEB1, KLF8 and enhancement the binding of HDAC1 in E-cadherin gene promoter, but DNA methylation is not responsible for the loss of E-cadherin. Catalase reduces Cr(VI)-induced E-cadherin and vimentin protein expression, attenuates cell invasion in matrigel and colony formation on soft agar. These results demonstrate that exposure to a common human carcinogen, Cr(VI), induces EMT and invasion during oncogenic transformation in lung epithelial cells and implicate in cancer metastasis and prevention. - Graphical abstract: Epithelialmesenchymal transition during oncogenic transformation induced by hexavalent chromium involves reactive oxygen species-dependent mechanisms in lung epithelial cells. - Highlights: We study if Cr(VI) might induce EMT and invasion in epithelial cells. Cr(VI) induces EMT by altering E-cadherin and vimentin expression. It also increases cell invasion and promotes oncogenic transformation. Catalase reduces Cr(VI)-induced EMT, invasion and transformation.

  11. Cellular morphometry of the bronchi of human and dog lungs. Annual progress report, April 1, 1992--March 31, 1993

    SciTech Connect (OSTI)

    Robbins, E.S.

    1992-09-01

    Quantitative data of the human bronchial epithelial cells at possible risk for malignant transformation in lung cancer is crucial for accurate radon dosimetry and risk analysis. The locations and other parameters of the nuclei which may be damaged by {alpha} particles must be determined and compared in different airway generations, among smokers, non-smokers and ex-smokers, between men and women and in people of different ages. This proposal includes extended morphometric studies on electron micrographs of human epithelium of defined airway generations and in parallel on electron micrographs of the dog bronchial lining. The second part of this proposal describes studies to quantitate the cycling bronchial epithelial population(s) using proliferation markers and immunocytochemistry on frozen and paraffin sections and similar labeling of isolated bronchial epithelial cells sorted flow cytometry.

  12. Radiobiologic comparison of helical tomotherapy, intensity modulated radiotherapy, and conformal radiotherapy in treating lung cancer accounting for secondary malignancy risks

    SciTech Connect (OSTI)

    Komisopoulos, Georgios; Mavroidis, Panayiotis; Rodriguez, Salvador; Stathakis, Sotirios; Papanikolaou, Nikos; Nikiforidis, Georgios C.; Sakellaropoulos, Georgios C.

    2014-01-01

    The aim of the present study is to examine the importance of using measures to predict the risk of inducing secondary malignancies in association with the clinical effectiveness of treatment plans in terms of tumor control and normal tissue complication probabilities. This is achieved by using radiobiologic parameters and measures, which may provide a closer association between clinical outcome and treatment delivery. Overall, 4 patients having been treated for lung cancer were examined. For each of them, 3 treatment plans were developed based on the helical tomotherapy (HT), multileaf collimator-based intensity modulated radiation therapy (IMRT), and 3-dimensional conformal radiation therapy (CRT) modalities. The different plans were evaluated using the complication-free tumor control probability (p{sub +}), the overall probability of injury (p{sub I}), the overall probability of control/benefit (p{sub B}), and the biologically effective uniform dose (D{sup }). These radiobiologic measures were used to develop dose-response curves (p-D{sup } diagram), which can help to evaluate different treatment plans when used in conjunction with standard dosimetric criteria. The risks for secondary malignancies in the heart and the contralateral lung were calculated for the 3 radiation modalities based on the corresponding dose-volume histograms (DVHs) of each patient. Regarding the overall evaluation of the different radiation modalities based on the p{sub +} index, the average values of the HT, IMRT, and CRT are 67.3%, 61.2%, and 68.2%, respectively. The corresponding average values of p{sub B} are 75.6%, 70.5%, and 71.0%, respectively, whereas the average values of p{sub I} are 8.3%, 9.3%, and 2.8%, respectively. Among the organs at risk (OARs), lungs show the highest probabilities for complications, which are 7.1%, 8.0%, and 1.3% for the HT, IMRT, and CRT modalities, respectively. Similarly, the biologically effective prescription doses (D{sub B}{sup }) for the HT, IMRT, and CRT modalities are 64.0, 60.9, and 60.8 Gy, respectively. Regarding the risk for secondary cancer, for the heart, the lowest average risk is produced by IMRT (0.10%) compared with the HT (0.17%) and CRT (0.12%) modalities, whereas the 3 radiation modalities show almost equivalent results regarding the contralateral lung (0.8% for HT, 0.9% for IMRT, and 0.9% for CRT). The use of radiobiologic parameters in the evaluation of different treatment plans and estimation of their expected clinical outcome is shown to provide very useful clinical information. The radiobiologic analysis of the response probabilities showed that different radiation modalities appear to be more effective in different patient geometries and target sizes and locations. Furthermore, there is not a clear pattern between the plans that appear to be more effective for the treatment and the risk of secondary malignancy. It seems that radiobiologically based treatment planning taking into account the risk of secondary cancer can be established as an effective clinical tool for a more clinically relevant treatment optimization.

  13. File:03ORBEasementsOnTrustAndNonTrustLand (2).pdf | Open Energy...

    Open Energy Info (EERE)

    file as it appeared at that time. DateTime Thumbnail Dimensions User Comment current 16:56, 10 December 2014 Thumbnail for version as of 16:56, 10 December 2014 1,275 1,650, 2...

  14. SU-F-BRD-05: Dosimetric Comparison of Protocol-Based SBRT Lung Treatment Modalities: Statistically Significant VMAT Advantages Over Fixed- Beam IMRT

    SciTech Connect (OSTI)

    Best, R; Harrell, A; Geesey, C; Libby, B; Wijesooriya, K

    2014-06-15

    Purpose: The purpose of this study is to inter-compare and find statistically significant differences between flattened field fixed-beam (FB) IMRT with flattening-filter free (FFF) volumetric modulated arc therapy (VMAT) for stereotactic body radiation therapy SBRT. Methods: SBRT plans using FB IMRT and FFF VMAT were generated for fifteen SBRT lung patients using 6 MV beams. For each patient, both IMRT and VMAT plans were created for comparison. Plans were generated utilizing RTOG 0915 (peripheral, 10 patients) and RTOG 0813 (medial, 5 patients) lung protocols. Target dose, critical structure dose, and treatment time were compared and tested for statistical significance. Parameters of interest included prescription isodose surface coverage, target dose heterogeneity, high dose spillage (location and volume), low dose spillage (location and volume), lung dose spillage, and critical structure maximum- and volumetric-dose limits. Results: For all criteria, we found equivalent or higher conformality with VMAT plans as well as reduced critical structure doses. Several differences passed a Student's t-test of significance: VMAT reduced the high dose spillage, evaluated with conformality index (CI), by an average of 9.4%15.1% (p=0.030) compared to IMRT. VMAT plans reduced the lung volume receiving 20 Gy by 16.2%15.0% (p=0.016) compared with IMRT. For the RTOG 0915 peripheral lesions, the volumes of lung receiving 12.4 Gy and 11.6 Gy were reduced by 27.0%13.8% and 27.5%12.6% (for both, p<0.001) in VMAT plans. Of the 26 protocol pass/fail criteria, VMAT plans were able to achieve an average of 0.20.7 (p=0.026) more constraints than the IMRT plans. Conclusions: FFF VMAT has dosimetric advantages over fixed beam IMRT for lung SBRT. Significant advantages included increased dose conformity, and reduced organs-at-risk doses. The overall improvements in terms of protocol pass/fail criteria were more modest and will require more patient data to establish difference trends of more statistical significance.

  15. Bacillus anthracis spores germinate extracellularly at air-liquid interface in an in vitro lung model under serum-free conditions

    SciTech Connect (OSTI)

    Powell, Joshua D.; Hutchison, Janine R.; Hess, Becky M.; Straub, Tim M.

    2015-07-30

    Aims: To better understand the parameters that govern spore dissemination after lung exposure using in vitro cell systems. Methods and Results: We evaluated the kinetics of uptake, germination and proliferation of B. anthracis Sterne spores in association with human primary lung epithelial cells, Calu-3, and A549 cell lines. We also analyzed the influence of various cell culture media formulations related to spore germination. Conclusions: We found negligible spore uptake by epithelial cells, but germination and proliferation of spores in the extracellular environment was evident, and was appreciably higher in A549 and Calu-3 cultures than in primary epithelial cells. Additionally, our results revealed spores in association with primary cells submerged in cell culture media germinated 1 h

  16. Bacillus anthracis spores germinate extracellularly at air-liquid interface in an in vitro lung model under serum-free conditions

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Powell, Joshua D.; Hutchison, Janine R.; Hess, Becky M.; Straub, Tim M.

    2015-07-30

    Aims: To better understand the parameters that govern spore dissemination after lung exposure using in vitro cell systems. Methods and Results: We evaluated the kinetics of uptake, germination and proliferation of B. anthracis Sterne spores in association with human primary lung epithelial cells, Calu-3, and A549 cell lines. We also analyzed the influence of various cell culture media formulations related to spore germination. Conclusions: We found negligible spore uptake by epithelial cells, but germination and proliferation of spores in the extracellular environment was evident, and was appreciably higher in A549 and Calu-3 cultures than in primary epithelial cells. Additionally, ourmore » results revealed spores in association with primary cells submerged in cell culture media germinated 1 h« less

  17. Precision Hypofractionated Radiation Therapy in Poor Performing Patients With Non-Small Cell Lung Cancer: Phase 1 Dose Escalation Trial

    SciTech Connect (OSTI)

    Westover, Kenneth D.; Loo, Billy W.; Gerber, David E.; Iyengar, Puneeth; Choy, Hak; Diehn, Maximilian; Hughes, Randy; Schiller, Joan; Dowell, Jonathan; Wardak, Zabi; Sher, David; Christie, Alana; Xie, Xian-Jin; Corona, Irma; Sharma, Akanksha; Wadsworth, Margaret E.; Timmerman, Robert

    2015-09-01

    Purpose: Treatment regimens for locally advanced non-small cell lung cancer (NSCLC) give suboptimal clinical outcomes. Technological advancements such as radiation therapy, the backbone of most treatment regimens, may enable more potent and effective therapies. The objective of this study was to escalate radiation therapy to a tumoricidal hypofractionated dose without exceeding the maximally tolerated dose (MTD) in patients with locally advanced NSCLC. Methods and Materials: Patients with stage II to IV or recurrent NSCLC and Eastern Cooperative Oncology Group performance status of 2 or greater and not candidates for surgical resection, stereotactic radiation, or concurrent chemoradiation were eligible. Highly conformal radiation therapy was given to treat intrathoracic disease in 15 fractions to a total of 50, 55, or 60 Gy. Results: Fifty-five patients were enrolled: 15 at the 50-Gy, 21 at the 55-Gy, and 19 at the 60-Gy dose levels. A 90-day follow-up was completed in each group without exceeding the MTD. With a median follow-up of 12.5 months, there were 93 grade ≥3 adverse events (AEs), including 39 deaths, although most AEs were considered related to factors other than radiation therapy. One patient from the 55- and 60-Gy dose groups developed grade ≥3 esophagitis, and 5, 4, and 4 patients in the respective dose groups experienced grade ≥3 dyspnea, but only 2 of these AEs were considered likely related to therapy. There was no association between fraction size and toxicity (P=.24). The median overall survival was 6 months with no significant differences between dose levels (P=.59). Conclusions: Precision hypofractionated radiation therapy consisting of 60 Gy in 15 fractions for locally advanced NSCLC is generally well tolerated. This treatment regimen could provide patients with poor performance status a potent alternative to chemoradiation. This study has implications for the cost effectiveness of lung cancer therapy. Additional studies of long-term safety and efficacy of this therapy are warranted.

  18. Over-expression of human endosulfatase-1 exacerbates cadmium-induced injury to transformed human lung cells in vitro

    SciTech Connect (OSTI)

    Zhang, Huiying; Department of Environmental and Molecular Toxicology, College of Agriculture and Life Sciences, NC State University, Raleigh, NC 27695 ; Newman, Donna R.; Bonner, James C.; Sannes, Philip L.

    2012-11-15

    Environmental exposure to cadmium is known to cause damage to alveolar epithelial cells of the lung, impair their capacity to repair, and result in permanent structural alterations. Cell surface heparan sulfate proteoglycans (HSPGs) can modulate cell responses to injury through their interactions with soluble effector molecules. These interactions are often sulfate specific, and the removal of sulfate groups from HS side chains could be expected to influence cellular injury, such as that caused by exposure to cadmium. The goal of this study was to define the role 6-O-sulfate plays in cellular responses to cadmium exposure in two pulmonary epithelial cancer cell lines (H292 and A549) and in normal human primary alveolar type II (hAT2) cells. Sulfate levels were modified by transduced transient over-expression of 6-O-endosulfatase (HSulf-1), a membrane-bound enzyme which specifically removes 6-O-sulfate groups from HSPG side chains. Results showed that cadmium decreased cell viability and activated apoptosis pathways at low concentrations in hAT2 cells but not in the cancer cells. HSulf-1 over-expression, on the contrary, decreased cell viability and activated apoptosis pathways in H292 and A549 cells but not in hAT2 cells. When combined with cadmium, HSulf-1 over-expression further decreased cell viability and exacerbated the activation of apoptosis pathways in the transformed cells but did not add to the toxicity in hAT2 cells. The finding that HSulf-1 sensitizes these cancer cells and intensifies the injury induced by cadmium suggests that 6-O-sulfate groups on HSPGs may play important roles in protection against certain environmental toxicants, such as heavy metals. -- Highlights: ? Primary human lung alveolar type 2 (hAT2) cells and H292 and A549 cells were used. ? Cadmium induced apoptosis in hAT2 cells but not in H292 or A549 cells. ? HSulf-1exacerbates apoptosis induced by cadmium in H292 and A549 but not hAT2 cells.

  19. SU-E-J-30: Benchmark Image-Based TCP Calculation for Evaluation of PTV Margins for Lung SBRT Patients

    SciTech Connect (OSTI)

    Li, M; Chetty, I; Zhong, H

    2014-06-01

    Purpose: Tumor control probability (TCP) calculated with accumulated radiation doses may help design appropriate treatment margins. Image registration errors, however, may compromise the calculated TCP. The purpose of this study is to develop benchmark CT images to quantify registration-induced errors in the accumulated doses and their corresponding TCP. Methods: 4DCT images were registered from end-inhale (EI) to end-exhale (EE) using a demons algorithm. The demons DVFs were corrected by an FEM model to get realistic deformation fields. The FEM DVFs were used to warp the EI images to create the FEM-simulated images. The two images combined with the FEM DVF formed a benchmark model. Maximum intensity projection (MIP) images, created from the EI and simulated images, were used to develop IMRT plans. Two plans with 3 and 5 mm margins were developed for each patient. With these plans, radiation doses were recalculated on the simulated images and warped back to the EI images using the FEM DVFs to get the accumulated doses. The Elastix software was used to register the FEM-simulated images to the EI images. TCPs calculated with the Elastix-accumulated doses were compared with those generated by the FEM to get the TCP error of the Elastix registrations. Results: For six lung patients, the mean Elastix registration error ranged from 0.93 to 1.98 mm. Their relative dose errors in PTV were between 0.28% and 6.8% for 3mm margin plans, and between 0.29% and 6.3% for 5mm-margin plans. As the PTV margin reduced from 5 to 3 mm, the mean TCP error of the Elastix-reconstructed doses increased from 2.0% to 2.9%, and the mean NTCP errors decreased from 1.2% to 1.1%. Conclusion: Patient-specific benchmark images can be used to evaluate the impact of registration errors on the computed TCPs, and may help select appropriate PTV margins for lung SBRT patients.

  20. Isotoxic Dose Escalation in the Treatment of Lung Cancer by Means of Heterogeneous Dose Distributions in the Presence of Respiratory Motion

    SciTech Connect (OSTI)

    Baker, Mariwan; Nielsen, Morten [Laboratory of Radiation Physics, Odense University Hospital, Odense (Denmark); Hansen, Olfred [Department of Oncology, Odense University Hospital, Odense (Denmark); Jahn, Jonas Westberg [Laboratory of Radiation Physics, Odense University Hospital, Odense (Denmark); Korreman, Stine [Department of Radiation Oncology, Copenhagen University Hospital, Copenhagen (Denmark); Brink, Carsten, E-mail: carsten.brink@ouh.regionsyddanmark.dk [Laboratory of Radiation Physics, Odense University Hospital, Odense (Denmark); Institute of Clinical Research, University of Southern Denmark, Odense (Denmark)

    2011-11-01

    Purpose: To test, in the presence of intrafractional respiration movement, a margin recipe valid for a homogeneous and conformal dose distribution and to test whether the use of smaller margins combined with heterogeneous dose distributions allows an isotoxic dose escalation when respiratory motion is considered. Methods and Materials: Twenty-three Stage II-III non-small-cell lung cancer patients underwent four-dimensional computed tomography scanning. The gross tumor volume and clinical target volume (CTV) were outlined in the mid-ventilation phase. The CTV-to-planning target volume (PTV) margin was calculated by use of a standard margin recipe and the patient-specific respiration pattern. Standard three-dimensional treatment plans were generated and recalculated on the remaining respiration phases. The planning was repeated for a CTV-to-PTV margin decreased by 2.5 and 5 mm relative to the initial margin in all directions. Time-averaged dose-volume histograms (four-dimensional dose-volume histograms) were calculated to evaluate the CTV-to-PTV margin. Finally, the dose was escalated in the plans with decreased PTV such that the mean lung dose (predictor of radiation-induced pneumonitis) was equal to mean lung dose in the plan by use of the initially calculated margin. Results: A reduction of the standard margin by 2.5 mm compared with the recipe resulted in too low of a minimum dose for some patients. A combination of dose escalation and use of heterogeneous dose distribution was able to increase the minimum dose to the target by approximately 10% and 20% for a CTV-to-PTV margin reduction of 2.5 mm and 5.0 mm, respectively. Conclusion: The margin recipe is valid for intrafractional respiration-induced tumor motions. It is possible to increase the dose to the target without increased mean lung dose with an inhomogeneous dose distribution.

  1. A preliminary regional PBPK model of lung metabolism for improving species dependent descriptions of 1,3-butadiene and its metabolites

    SciTech Connect (OSTI)

    Campbell, Jerry; Van Landingham, Cynthia; Crowell, Susan; Gentry, Robinan; Kaden, Debra; Fiebelkorn, Stacy; Loccisano, Anne; Clewell, Harvey

    2015-06-12

    1,3-Butadiene (BD), a volatile organic chemical (VOC), is used in synthetic rubber production and other industrial processes. It is detectable at low levels in ambient air as well as in tobacco smoke and gasoline vapors. Inhalation exposures to high concentrations of BD have been associated with lung cancer in both humans and experimental animals, although differences in species sensitivity have been observed. Metabolically active lung cells such as Pulmonary Type I and Type II epithelial cells and club cells (Clara cells)1 are potential targets of BD metabolite-induced toxicity. Metabolic capacities of these cells, their regional densities, and distributions vary throughout the respiratory tract as well as between species and cell types. Here we present a physiologically based pharmacokinetic (PBPK) model for BD that includes a regional model of lung metabolism, based on a previous model for styrene, to provide species-dependent descriptions of BD metabolism in the mouse, rat, and human. Since there are no in vivo data on BD pharmacokinetics in the human, the rat and mouse models were parameterized to the extent possible on the basis of in vitro metabolic data. Where it was necessary to use in vivo data, extrapolation from rat to mouse was performed to evaluate the level of uncertainty in the human model. A kidney compartment and description of downstream metabolism were also included in the model to allow for eventual use of available urinary and blood biomarker data in animals and humans to calibrate the model for estimation of BD exposures and internal metabolite levels. Results from simulated inhalation exposures to BD indicate that incorporation of differential lung region metabolism is important in describing species differences in pulmonary response and that these differences may have implications for risk assessments of human exposures to BD.

  2. A preliminary regional PBPK model of lung metabolism for improving species dependent descriptions of 1,3-butadiene and its metabolites

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Campbell, Jerry; Van Landingham, Cynthia; Crowell, Susan; Gentry, Robinan; Kaden, Debra; Fiebelkorn, Stacy; Loccisano, Anne; Clewell, Harvey

    2015-06-12

    1,3-Butadiene (BD), a volatile organic chemical (VOC), is used in synthetic rubber production and other industrial processes. It is detectable at low levels in ambient air as well as in tobacco smoke and gasoline vapors. Inhalation exposures to high concentrations of BD have been associated with lung cancer in both humans and experimental animals, although differences in species sensitivity have been observed. Metabolically active lung cells such as Pulmonary Type I and Type II epithelial cells and club cells (Clara cells)1 are potential targets of BD metabolite-induced toxicity. Metabolic capacities of these cells, their regional densities, and distributions vary throughoutmore » the respiratory tract as well as between species and cell types. Here we present a physiologically based pharmacokinetic (PBPK) model for BD that includes a regional model of lung metabolism, based on a previous model for styrene, to provide species-dependent descriptions of BD metabolism in the mouse, rat, and human. Since there are no in vivo data on BD pharmacokinetics in the human, the rat and mouse models were parameterized to the extent possible on the basis of in vitro metabolic data. Where it was necessary to use in vivo data, extrapolation from rat to mouse was performed to evaluate the level of uncertainty in the human model. A kidney compartment and description of downstream metabolism were also included in the model to allow for eventual use of available urinary and blood biomarker data in animals and humans to calibrate the model for estimation of BD exposures and internal metabolite levels. Results from simulated inhalation exposures to BD indicate that incorporation of differential lung region metabolism is important in describing species differences in pulmonary response and that these differences may have implications for risk assessments of human exposures to BD.« less

  3. Associations of symptoms related to isocyanate, ureaformol, and formophenolic exposures with respiratory symptoms and lung function in coal miners

    SciTech Connect (OSTI)

    Bertrand, J.P.; Simon, V.; Chau, N.

    2007-04-15

    The respiratory effects of diphenylmethane diisocyanate (MDI)-based resins and ureaformol- and formophenolic-based resins, used in coal mining, are unknown. This cross-sectional study of 354 miners evaluated respiratory health in miners with MDI-related symptoms (IS) and ureaformol/formophenolic-related symptoms (UFS). The protocol included clinical examination, chest radiograph, questionnaire on respiratory symptoms, smoking habit, job history, resin handling, and spirometry. Resin handling concerned 27.7% of the miners. IS affected 5.6%, and 1.4% also after work. UFS affected 22.6%, and 2.3% also after work. Wheezing affected 35.6%; chronic cough, expectoration, or bronchitis about 10%; dyspnea 5.4%; and asthma 2.8%. The miners with UFS had significantly more frequent chronic cough, expectoration, chronic bronchitis, dyspnea, and wheezing, whereas those with IS at and after work had markedly lower FVC, FEV1, MMEF, FEF50% and FEF25%. These findings raise the possibility of deleterious effects of exposures to MDI and ureaformol/ ormophenolic resins on respiratory health and lung function in coal miners during their working life.

  4. SU-E-T-606: A Novel Integrated VMAT/IMRT Technique For the Treatment of Non-Small Cell Lung Cancer

    SciTech Connect (OSTI)

    Zhao, N; Yang, R; Wang, J

    2014-06-01

    Purpose: To investigate a novel Integrated VMAT/IMRT technique which combines volumetric modulated arc therapy (VMAT) and intensity modulated radiation therapy (IMRT) for non-small cell lung cancer (NSCLC). Methods: 2 partial arcs VMAT, 5-field IMRT and Integrated VMAT/IMRT plans were created for 17 patients with NSCLC. The Integrated VMAT/IMRT technique consisted of 2 partial VMAT arcs and 5 IMRT fields. The dose distribution of planning target volume (PTV) and organs at risk (OARs) for Integrated VMAT/IMRT was compared with IMRT and VMAT. The monitor units (MUs) and treatment delivery time were also evaluated. For each plan, a dry run was performed to assess the dosimetric accuracy with MatriXX from IBA. Results: Integrated VMAT/IMRT significantly improved the target conformity and homogeneity. The V30 of normal lung for Integrated plans was significantly lower than IMRT plans (8.4% vs 9.2%; p<0.05). The V5 and mean lung dose (MLD) of normal lung for Integrated plans were 9.8% and 4.6% lower than VMAT plans (p<0.05). The maximum dose of spinal cord for Integrated plans was 4.9 Gy lower than IMRT plans (p<0.05). The mean delivery time of IMRT, VMAT and Integrated plans was 280 s, 114 s, and 327 s, respectively. The mean MUs needed for IMRT, VMAT and Integrated plans were 933, 512, and 737, respectively. The gamma pass rates were beyond 90% at the 3%/3 mm criteria when the gantry angles were set to 0 for pretreatment verification. Conclusion: Integrated VMAT/IMRT technique significantly reduced V5, V10 and MLD of normal lung compared with VMAT, and the irradiated volume of the OARs receiving medium to high dose with fewer MUs compared with IMRT. Integrated VMAT/IMRT technique can be a feasible radiotherapy technique with better plan quality and accurately delivered on the linear accelerator. Ruijie Yang was funded by the grant project: National Natural Science Foundation of China (No. 81071237). Other authors have no competing interest for this work.

  5. Comparative Effectiveness of 5 Treatment Strategies for Early-Stage Non-Small Cell Lung Cancer in the Elderly

    SciTech Connect (OSTI)

    Shirvani, Shervin M.; Jiang, Jing; Chang, Joe Y.; Welsh, James W.; Gomez, Daniel R.; Swisher, Stephen; Buchholz, Thomas A.; Smith, Benjamin D.

    2012-12-01

    Purpose: The incidence of early-stage non-small cell lung cancer (NSCLC) among older adults is expected to increase because of demographic trends and computed tomography-based screening; yet, optimal treatment in the elderly remains controversial. Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare cohort spanning 2001-2007, we compared survival outcomes associated with 5 strategies used in contemporary practice: lobectomy, sublobar resection, conventional radiation therapy, stereotactic ablative radiation therapy (SABR), and observation. Methods and Materials: Treatment strategy and covariates were determined in 10,923 patients aged {>=}66 years with stage IA-IB NSCLC. Cox regression, adjusted for patient and tumor factors, compared overall and disease-specific survival for the 5 strategies. In a second exploratory analysis, propensity-score matching was used for comparison of SABR with other options. Results: The median age was 75 years, and 29% had moderate to severe comorbidities. Treatment distribution was lobectomy (59%), sublobar resection (11.7%), conventional radiation (14.8%), observation (12.6%), and SABR (1.1%). In Cox regression analysis with a median follow-up time of 3.2 years, SABR was associated with the lowest risk of death within 6 months of diagnosis (hazard ratio [HR] 0.48; 95% confidence interval [CI] 0.38-0.63; referent is lobectomy). After 6 months, lobectomy was associated with the best overall and disease-specific survival. In the propensity-score matched analysis, survival after SABR was similar to that after lobectomy (HR 0.71; 95% CI 0.45-1.12; referent is SABR). Conventional radiation and observation were associated with poor outcomes in all analyses. Conclusions: In this population-based experience, lobectomy was associated with the best long-term outcomes in fit elderly patients with early-stage NSCLC. Exploratory analysis of SABR early adopters suggests efficacy comparable with that of surgery in select populations. Evaluation of these therapies in randomized trials is urgently needed.

  6. Brachial Plexopathy in Apical Non-Small Cell Lung Cancer Treated With Definitive Radiation: Dosimetric Analysis and Clinical Implications

    SciTech Connect (OSTI)

    Eblan, Michael J.; Corradetti, Michael N.; Lukens, J. Nicholas; Xanthopoulos, Eric; Mitra, Nandita; Christodouleas, John P.; Grover, Surbhi; Fernandes, Annemarie T.; Langer, Corey J.; Evans, Tracey L.; Stevenson, James; Rengan, Ramesh; Apisarnthanarax, Smith

    2013-01-01

    Purpose: Data are limited on the clinical significance of brachial plexopathy in patients with apical non-small cell lung cancers (NSCLC) treated with definitive radiation therapy. We report the rates of radiation-induced brachial plexopathy (RIBP) and tumor-related brachial plexopathy (TRBP) and associated dosimetric parameters in apical NSCLC patients. Methods and Materials: Charts of NSCLC patients with primary upper lobe or superiorly located nodal disease who received {>=}50 Gy of definitive conventionally fractionated radiation or chemoradiation were retrospectively reviewed for evidence of brachial plexopathy and categorized as RIBP, TRBP, or trauma-related. Dosimetric data were gathered on ipsilateral brachial plexuses (IBP) contoured according to Radiation Therapy Oncology Group atlas guidelines. Results: Eighty patients were identified with a median follow-up and survival time of 17.2 and 17.7 months, respectively. The median prescribed dose was 66.6 Gy (range, 50.4-84.0), and 71% of patients received concurrent chemotherapy. RIBP occurred in 5 patients with an estimated 3-year rate of 12% when accounting for competing risk of death. Seven patients developed TRBP (estimated 3-year rate of 13%), comprising 24% of patients who developed locoregional failures. Grade 3 brachial plexopathy was more common in patients who experienced TRBP than RIBP (57% vs 20%). No patient who received {<=}78 Gy to the IBP developed RIBP. On multivariable competing risk analysis, IBP V76 receiving {>=}1 cc, and primary tumor failure had the highest hazard ratios for developing RIBP and TRBP, respectively. Conclusions: RIBP is a relatively uncommon complication in patients with apical NSCLC tumors receiving definitive doses of radiation, while patients who develop primary tumor failures are at high risk for developing morbid TRBP. These findings suggest that the importance of primary tumor control with adequate doses of radiation outweigh the risk of RIBP in this population of patients.

  7. Use of Stereotactic Radiosurgery for Brain Metastases From Non-Small Cell Lung Cancer in the United States

    SciTech Connect (OSTI)

    Halasz, Lia M.; Weeks, Jane C.; Neville, Bridget A.; Taback, Nathan; Punglia, Rinaa S.

    2013-02-01

    Purpose: The indications for treatment of brain metastases from non-small cell lung cancer (NSCLC) with stereotactic radiosurgery (SRS) remain controversial. We studied patterns, predictors, and cost of SRS use in elderly patients with NSCLC. Methods and Materials: Using the Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database, we identified patients with NSCLC who were diagnosed with brain metastases between 2000 and 2007. Our cohort included patients treated with radiation therapy and not surgical resection as initial treatment for brain metastases. Results: We identified 7684 patients treated with radiation therapy within 2 months after brain metastases diagnosis, of whom 469 (6.1%) cases had billing codes for SRS. Annual SRS use increased from 3.0% in 2000 to 8.2% in 2005 and varied from 3.4% to 12.5% by specific SEER registry site. After controlling for clinical and sociodemographic characteristics, we found SRS use was significantly associated with increasing year of diagnosis, specific SEER registry, higher socioeconomic status, admission to a teaching hospital, no history of participation in low-income state buy-in programs (a proxy for Medicaid eligibility), no extracranial metastases, and longer intervals from NSCLC diagnosis. The average cost per patient associated with radiation therapy was 2.19 times greater for those who received SRS than for those who did not. Conclusions: The use of SRS in patients with metastatic NSCLC increased almost 3-fold from 2000 to 2005. In addition, we found significant variations in SRS use across SEER registries and socioeconomic quartiles. National practice patterns in this study suggested both a lack of consensus and an overall limited use of the approach among elderly patients before 2008.

  8. Role of curative radiotherapy in the treatment of lung cancer. [Clinical factors effecting efficacy and incidence of complications

    SciTech Connect (OSTI)

    Coy, P.; Kennelly, G.M.

    1980-02-15

    From 1963 to 1974, 141 patients with lung cancer were treated with curative intent in the A. Maxwell Evans Clinic in Vancouver. The clinical presentation, age and sex distribution, histology, and reasons for surgery not being carried out are examined. The results of this treatment are presented. An attempt has been made to isolate a group of patients who have a better prognosis so that treatment selection can be improved. Hemoptysis, cough, dyspnea, and incidental finding on routine chest x-ray were the most common manner of presentation. Thirty-four percent of the patients were over 70 years of age and 13% were women. The crude overall three- and five-year survival rates were 18 and 10% (19 and 9% in the men, 17 and 14% in the women). Patients presenting with dyspnea had a better survival than those presenting with cough and hemoptysis. Patients with lesions less than 3 cm in diameter had a 28% three-year survival, compared with 14% for lesions greater than 5 cm in diameter. The three- and five-year survival rates in patients over 70 years of age were 23 and 17% respectively. The response to treatment and the survival were better in the patients with squamous cell carcinoma. Twenty-two percent were alive at three years and 12% at five years as compared with 9 and 5% for other histologies. Fifty-four percent of the 35 patients with a complete response and with squamous cell carcinoma were alive at three years, compared with only 8% of the 12 patients with other histologies who showed a complete response.

  9. ATM Polymorphisms Predict Severe Radiation Pneumonitis in Patients With Non-Small Cell Lung Cancer Treated With Definitive Radiation Therapy

    SciTech Connect (OSTI)

    Xiong, Huihua; Liao, Zhongxing; Liu, Zhensheng; Xu, Ting; Wang, Qiming; Liu, Hongliang; Komaki, Ritsuko; Gomez, Daniel; Wang, Li-E; Wei, Qingyi

    2013-03-15

    Purpose: The ataxia telangiectasia mutated (ATM) gene mediates detection and repair of DNA damage. We investigated associations between ATM polymorphisms and severe radiation-induced pneumonitis (RP). Methods and Materials: We genotyped 3 potentially functional single nucleotide polymorphisms (SNPs) of ATM (rs1801516 [D1853N/5557G>A], rs189037 [-111G>A] and rs228590) in 362 patients with non-small cell lung cancer (NSCLC), who received definitive (chemo)radiation therapy. The cumulative severe RP probabilities by genotypes were evaluated using the Kaplan-Meier analysis. The associations between severe RP risk and genotypes were assessed by both logistic regression analysis and Cox proportional hazard model with time to event considered. Results: Of 362 patients (72.4% of non-Hispanic whites), 56 (15.5%) experienced grade ≥3 RP. Patients carrying ATM rs189037 AG/GG or rs228590 TT/CT genotypes or rs189037G/rs228590T/rs1801516G (G-T-G) haplotype had a lower risk of severe RP (rs189037: GG/AG vs AA, adjusted hazard ratio [HR] = 0.49, 95% confidence interval [CI], 0.29-0.83, P=.009; rs228590: TT/CT vs CC, HR=0.57, 95% CI, 0.33-0.97, P=.036; haplotype: G-T-G vs A-C-G, HR=0.52, 95% CI, 0.35-0.79, P=.002). Such positive findings remained in non-Hispanic whites. Conclusions: ATM polymorphisms may serve as biomarkers for susceptibility to severe RP in non-Hispanic whites. Large prospective studies are required to confirm our findings.

  10. SU-E-J-265: Practical Issues and Solutions in Reconstructing and Using 4DCT for Radiotherapy Planning of Lung Cancer

    SciTech Connect (OSTI)

    Lu, W; Feigenberg, S; Yi, B; Lasio, G; Prado, K; D'Souza, W

    2014-06-01

    Purpose: To report practical issues and solutions in reconstructing and using 4DCT to account for respiratory motion in radiotherapy planning. Methods: Quiet breathing 4DCT was used to account for respiratory motion for patients with lung or upper abdomen tumor. A planning CT and a 4DCT were acquired consecutively with a Philips Brilliance CT scanner and Varian RPM System. The projections were reconstructed into 10 phases. In Pinnacle RTP system, we contour a GTV in each phase and unite all 10 GTVs as ITV. The ITV is then mapped to the planning CT. We describe practical issues, their causes, our solutions and reasoning during this process. Results: In 6 months, 9 issues were reported for 8 patients with lung cancer. For two patients, part of the GTV (?50% and 10%) in planning CT fell outside the ITV in 4DCT. There was a 7 mm variation in first patient back position because less restricted immobilization had to be used. The second discrepancy was due to moderate variation in breathing amplitude. We extended the ITV to include the GTV since both variations may likely happen during treatment. A LUL tumor showed no motion due to a 10-s long no-breathing period. An RLL tumor appeared double due to an abnormally deeper breath at the tumor region. We repeated 4DCT reiterating the importance of quiet, regular breathing. One patient breathed too light to generate RPM signal. Two issues (no motion in lung, incomplete images in 90% phase) were due to incorrect tag positions. Two unexplainable errors disappeared when repeating reconstruction. In summary, 5 issues were patient-related and 4 were technique issues. Conclusion: Improving breathing regularity avoided large artifacts in 4DCT. One needs to closely monitor patient breathing. For uncontrollable variations, larger PTVs are necessary which requires appropriate communication between physics and the treating physician.

  11. Consideration of Dose Limits for Organs at Risk of Thoracic Radiotherapy: Atlas for Lung, Proximal Bronchial Tree, Esophagus, Spinal Cord, Ribs, and Brachial Plexus

    SciTech Connect (OSTI)

    Kong, Feng-Ming; Ritter, Timothy; Quint, Douglas J.; Senan, Suresh; Gaspar, Laurie E.; Komaki, Ritsuko U.; Hurkmans, Coen W.; Timmerman, Robert; Bezjak, Andrea; Bradley, Jeffrey D.; Movsas, Benjamin; Marsh, Lon; Okunieff, Paul; Choy, Hak; Curran, Walter J.

    2011-12-01

    Purpose: To review the dose limits and standardize the three-dimenional (3D) radiographic definition for the organs at risk (OARs) for thoracic radiotherapy (RT), including the lung, proximal bronchial tree, esophagus, spinal cord, ribs, and brachial plexus. Methods and Materials: The present study was performed by representatives from the Radiation Therapy Oncology Group, European Organization for Research and Treatment of Cancer, and Soutwestern Oncology Group lung cancer committees. The dosimetric constraints of major multicenter trials of 3D-conformal RT and stereotactic body RT were reviewed and the challenges of 3D delineation of these OARs described. Using knowledge of the human anatomy and 3D radiographic correlation, draft atlases were generated by a radiation oncologist, medical physicist, dosimetrist, and radiologist from the United States and reviewed by a radiation oncologist and medical physicist from Europe. The atlases were then critically reviewed, discussed, and edited by another 10 radiation oncologists. Results: Three-dimensional descriptions of the lung, proximal bronchial tree, esophagus, spinal cord, ribs, and brachial plexus are presented. Two computed tomography atlases were developed: one for the middle and lower thoracic OARs (except for the heart) and one focusing on the brachial plexus for a patient positioned supine with their arms up for thoracic RT. The dosimetric limits of the key OARs are discussed. Conclusions: We believe these atlases will allow us to define OARs with less variation and generate dosimetric data in a more consistent manner. This could help us study the effect of radiation on these OARs and guide high-quality clinical trials and individualized practice in 3D-conformal RT and stereotactic body RT.

  12. Critical dose and toxicity index of organs at risk in radiotherapy: Analyzing the calculated effects of modified dose fractionation in nonsmall cell lung cancer

    SciTech Connect (OSTI)

    Pedicini, Piernicola; Strigari, Lidia; Benassi, Marcello; Caivano, Rocchina; Fiorentino, Alba; Nappi, Antonio; Salvatore, Marco; Storto, Giovanni

    2014-04-01

    To increase the efficacy of radiotherapy for nonsmall cell lung cancer (NSCLC), many schemes of dose fractionation were assessed by a new toxicity index (I), which allows one to choose the fractionation schedules that produce less toxic treatments. Thirty-two patients affected by non resectable NSCLC were treated by standard 3-dimensional conformal radiotherapy (3DCRT) with a strategy of limited treated volume. Computed tomography datasets were employed to re plan by simultaneous integrated boost intensity-modulated radiotherapy (IMRT). The dose distributions from plans were used to test various schemes of dose fractionation, in 3DCRT as well as in IMRT, by transforming the dose-volume histogram (DVH) into a biological equivalent DVH (BDVH) and by varying the overall treatment time. The BDVHs were obtained through the toxicity index, which was defined for each of the organs at risk (OAR) by a linear quadratic model keeping an equivalent radiobiological effect on the target volume. The less toxic fractionation consisted in a severe/moderate hyper fractionation for the volume including the primary tumor and lymph nodes, followed by a hypofractionation for the reduced volume of the primary tumor. The 3DCRT and IMRT resulted, respectively, in 4.7% and 4.3% of dose sparing for the spinal cord, without significant changes for the combined-lungs toxicity (p < 0.001). Schedules with reduced overall treatment time (accelerated fractionations) led to a 12.5% dose sparing for the spinal cord (7.5% in IMRT), 8.3% dose sparing for V{sub 20} in the combined lungs (5.5% in IMRT), and also significant dose sparing for all the other OARs (p < 0.001). The toxicity index allows to choose fractionation schedules with reduced toxicity for all the OARs and equivalent radiobiological effect for the tumor in 3DCRT, as well as in IMRT, treatments of NSCLC.

  13. Functional Promoter Variant rs2868371 of HSPB1 Is Associated With Risk of Radiation Pneumonitis After Chemoradiation for Non-Small Cell Lung Cancer

    SciTech Connect (OSTI)

    Pang, Qingsong; Department of Radiation Oncology and Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin ; Wei, Qingyi; Xu, Ting; Yuan, Xianglin; Lopez Guerra, Jose Luis; Levy, Lawrence B.; Liu, Zhensheng; Gomez, Daniel R.; Zhuang, Yan; Wang, Li-E.; Mohan, Radhe; Komaki, Ritsuko; Liao, Zhongxing

    2013-04-01

    Purpose: To date, no biomarkers have been found to predict, before treatment, which patients will develop radiation pneumonitis (RP), a potentially fatal toxicity, after chemoradiation for lung cancer. We investigated potential associations between single nucleotide polymorphisms (SNPs) in HSPB1 and risk of RP after chemoradiation for non-small cell lung cancer (NSCLC). Methods and Materials: Subjects were patients with NSCLC treated with chemoradiation at 1 institution. The training data set comprised 146 patients treated from 1999 to July 2004; the validation data set was 125 patients treated from August 2004 to March 2010. We genotyped 2 functional SNPs of HSPB1 (rs2868370 and rs2868371) from all patients. We used Kaplan-Meier analysis to assess the risk of grade ≥2 or ≥3 RP in both data sets and a parametric log-logistic survival model to evaluate the association of HSPB1 genotypes with that risk. Results: Grade ≥3 RP was experienced by 13% of those with CG/GG and 29% of those with CC genotype of HSPB1 rs2868371 in the training data set (P=.028); corresponding rates in the validation data set were 2% CG/GG and 14% CC (P=.02). Univariate and multivariate analysis confirmed the association of CC of HSPB1 rs2868371 with higher risk of grade ≥3 RP than CG/GG after adjustment for sex, age, performance status, and lung mean dose. This association was validated both in the validation data set and with Harrell's C statistic. Conclusions: The CC genotype of HSPB1 rs2868371 was associated with severe RP after chemoradiation for NSCLC.

  14. Stereotactic Body Radiation Therapy Can Be Used Safely to Boost Residual Disease in Locally Advanced Non-Small Cell Lung Cancer: A Prospective Study

    SciTech Connect (OSTI)

    Feddock, Jonathan; Arnold, Susanne M.; Department of Medical Oncology, University of Kentucky, Lexington, Kentucky ; Shelton, Brent J.; Sinha, Partha; Conrad, Gary; Chen, Li; Rinehart, John; McGarry, Ronald C.

    2013-04-01

    Purpose: To report the results of a prospective, single-institution study evaluating the feasibility of conventional chemoradiation (CRT) followed by stereotactic body radiation therapy (SBRT) as a means of dose escalation for patients with stage II-III non-small cell lung cancer (NSCLC) with residual disease. Methods and Materials: Patients without metastatic disease and with radiologic evidence of limited residual disease (?5 cm) within the site of the primary tumor and good or complete nodal responses after standard CRT to a target dose of 60 Gy were considered eligible. The SBRT boost was done to achieve a total combined dose biological equivalent dose >100 Gy to the residual primary tumor, consisting of 10 Gy 2 fractions (20 Gy total) for peripheral tumors, and 6.5 Gy 3 fractions (19.5 Gy total) for medial tumors using the Radiation Therapy Oncology Group protocol 0813 definitions. The primary endpoint was the development of grade ?3 radiation pneumonitis (RP). Results: After a median follow-up of 13 months, 4 patients developed acute grade 3 RP, and 1 (2.9%) developed late and persistent grade 3 RP. No patients developed grade 4 or 5 RP. Mean lung dose, V2.5, V5, V10, and V20 values were calculated for the SBRT boost, and none were found to significantly predict for RP. Only advancing age (P=.0147), previous smoking status (P=.0505), and high CRT mean lung dose (P=.0295) were significantly associated with RP development. At the time of analysis, the actuarial local control rate at the primary tumor site was 82.9%, with only 6 patients demonstrating recurrence. Conclusions: Linear accelerator-based SBRT for dose escalation of limited residual NSCLC after definitive CRT was feasible and did not increase the risk for toxicity above that for standard radiation therapy.

  15. SU-F-BRD-09: Is It Sufficient to Use Only Low Density Tissue-Margin to Compensate Inter-Fractionation Setup Uncertainties in Lung Treatment?

    SciTech Connect (OSTI)

    Nie, K; Yue, N; Chen, T; Millevoi, R; Qin, S; Guo, J

    2014-06-15

    Purpose: In lung radiation treatment, PTV is formed with a margin around GTV (or CTV/ITV). Although GTV is most likely of water equivalent density, the PTV margin may be formed with the surrounding low-density tissues, which may lead to unreal dosimetric plan. This study is to evaluate whether the concern of dose calculation inside the PTV with only low density margin could be justified in lung treatment. Methods: Three SBRT cases were analyzed. The PTV from the original plan (Plan-O) was created with a 510 mm margin outside the ITV to incorporate setup errors and all mobility from 10 respiratory phases. Test plans were generated with the GTV shifted to the PTV edge to simulate the extreme situations with maximum setup uncertainties. Two representative positions as the very posterior-superior (Plan-PS) and anterior-inferior (Plan-AI) edge were considered. The virtual GTV was assigned a density of 1.0 g.cm?3 and surrounding lung, including the PTV margin, was defined as 0.25 g.cm?3. Also, additional plan with a 1mm tissue-margin instead of full lung-margin was created to evaluate whether a composite-margin (Plan-Comp) has a better approximation for dose calculation. All plans were generated on the average CT using Analytical Anisotropic Algorithm with heterogeneity correction on and all planning parameters/monitor unites remained unchanged. DVH analyses were performed for comparisons. Results: Despite the non-static dose distribution, the high-dose region synchronized with tumor positions. This might due to scatter conditions as greater doses were absorbed in the solid-tumor than in the surrounding low-density lungtissue. However, it still showed missing target coverage in general. Certain level of composite-margin might give better approximation for the dosecalculation. Conclusion: Our exploratory results suggest that with the lungmargin only, the planning dose of PTV might overestimate the coverage of the target during treatment. The significance of this overestimation might warrant further investigation.

  16. Reactive oxygen species produced by NADPH oxidase and mitochondrial dysfunction in lung after an acute exposure to Residual Oil Fly Ashes

    SciTech Connect (OSTI)

    Magnani, Natalia D.; Marchini, Timoteo; Vanasco, Virginia; Tasat, Deborah R.; Alvarez, Silvia; Evelson, Pablo

    2013-07-01

    Reactive O{sub 2} species production triggered by particulate matter (PM) exposure is able to initiate oxidative damage mechanisms, which are postulated as responsible for increased morbidity along with the aggravation of respiratory diseases. The aim of this work was to quantitatively analyse the major sources of reactive O{sub 2} species involved in lung O{sub 2} metabolism after an acute exposure to Residual Oil Fly Ashes (ROFAs). Mice were intranasally instilled with a ROFA suspension (1.0 mg/kg body weight), and lung samples were analysed 1 h after instillation. Tissue O{sub 2} consumption and NADPH oxidase (Nox) activity were evaluated in tissue homogenates. Mitochondrial respiration, respiratory chain complexes activity, H{sub 2}O{sub 2} and ATP production rates, mitochondrial membrane potential and oxidative damage markers were assessed in isolated mitochondria. ROFA exposure was found to be associated with 61% increased tissue O{sub 2} consumption, a 30% increase in Nox activity, a 33% increased state 3 mitochondrial O{sub 2} consumption and a mitochondrial complex II activity increased by 25%. During mitochondrial active respiration, mitochondrial depolarization and a 53% decreased ATP production rate were observed. Neither changes in H{sub 2}O{sub 2} production rate, nor oxidative damage in isolated mitochondria were observed after the instillation. After an acute ROFA exposure, increased tissue O{sub 2} consumption may account for an augmented Nox activity, causing an increased O{sub 2}{sup ?} production. The mitochondrial function modifications found may prevent oxidative damage within the organelle. These findings provide new insights to the understanding of the mechanisms involving reactive O{sub 2} species production in the lung triggered by ROFA exposure. - Highlights: Exposure to ROFA alters the oxidative metabolism in mice lung. The augmented Nox activity contributes to the high tissue O{sub 2} consumption. Exposure to ROFA produces alterations in mitochondrial function. ??{sub m} decrease in state 3 may be responsible for the decreased ATP production. Mild uncoupling prevents mitochondrial oxidative damage.

  17. Nitrative DNA damage induced by multi-walled carbon nanotube via endocytosis in human lung epithelial cells

    SciTech Connect (OSTI)

    Guo, Feiye; Ma, Ning; Horibe, Yoshiteru; Kawanishi, Shosuke; Murata, Mariko; Hiraku, Yusuke

    2012-04-15

    Carbon nanotube (CNT) has a promising usage in the field of material science for industrial purposes because of its unique physicochemical property. However, intraperitoneal administration of CNT was reported to cause mesothelioma in experimental animals. Chronic inflammation may contribute to carcinogenesis induced by fibrous materials. 8-Nitroguanine is a mutagenic DNA lesion formed during inflammation and may play a role in CNT-induced carcinogenesis. In this study, we examined 8-nitroguanine formation in A549 human lung alveolar epithelial cells treated with multi-walled CNT (MWCNT) by fluorescent immunocytochemistry. Both MWCNTs with diameter of 2030 nm (CNT20) and 4070 nm (CNT40) significantly induced 8-nitroguanine formation at 5 and 10 ?g/ml (p < 0.05), which persisted for 24 h, although there was no significant difference in DNA-damaging abilities of these MWCNTs. MWCNTs significantly induced the expression of inducible nitric oxide synthase (iNOS) for 24 h (p < 0.05). MWCNTs also significantly increased the level of nitrite, a hydrolysis product of oxidized NO, in the culture supernatant at 4 and 8 h (p < 0.05). MWCNT-induced 8-nitroguanine formation and iNOS expression were largely suppressed by inhibitors of iNOS (1400 W), nuclear factor-?B (Bay11-7082), actin polymerization (cytochalasin D), caveolae-mediated endocytosis (methyl-?-cyclodextrin, MBCD) and clathrin-mediated endocytosis (monodansylcadaverine, MDC). Electron microscopy revealed that MWCNT was mainly located in vesicular structures in the cytoplasm, and its cellular internalization was reduced by MBCD and MDC. These results suggest that MWCNT is internalized into cells via clathrin- and caveolae-mediated endocytosis, leading to inflammatory reactions including iNOS expression and resulting nitrative DNA damage, which may contribute to carcinogenesis. Highlights: ?Multi-walled carbon nanotube (MWCNT) caused DNA damage in A549 cells. ?MWCNT formed 8-nitroguanine, a DNA lesion associated with inflammatory response. ?MWCNT was internalized into cells via caveolin- and clathrin-mediated endocytosis. ?8-Nitroguanine formation and iNOS expression involved these types of endocytosis. ?Internalized MWCNT plays a key role in inflammatory response and DNA damage.

  18. Role of reactive oxygen species in arsenic-induced transformation of human lung bronchial epithelial (BEAS-2B) cells

    SciTech Connect (OSTI)

    Zhang, Zhuo; Pratheeshkumar, Poyil; Budhraja, Amit; Son, Young-Ok; Kim, Donghern; Shi, Xianglin

    2015-01-09

    Highlights: Short term exposure of cells to arsenic causes ROS generation. Chronical exposure of cells to arsenic causes malignant cell transformation. Inhibition of ROS generation reduces cell transformation by arsenic. Arsenic-transformed cells exhibit reduced capacity of generating ROS. Arsenic-transformed cells exhibit increased levels of antioxidants. - Abstract: Arsenic is an environmental carcinogen, its mechanisms of carcinogenesis remain to be investigated. Reactive oxygen species (ROS) are considered to be important. A previous study (Carpenter et al., 2011) has measured ROS level in human lung bronchial epithelial (BEAS-2B) cells and arsenic-transformed BEAS-2B cells and found that ROS levels were higher in transformed cells than that in parent normal cells. Based on these observations, the authors concluded that cell transformation induced by arsenic is mediated by increased cellular levels of ROS. This conclusion is problematic because this study only measured the basal ROS levels in transformed and parent cells and did not investigate the role of ROS in the process of arsenic-induced cell transformation. The levels of ROS in arsenic-transformed cells represent the result and not the cause of cell transformation. Thus question concerning whether ROS are important in arsenic-induced cell transformation remains to be answered. In the present study, we used expressions of catalase (antioxidant against H{sub 2}O{sub 2}) and superoxide dismutase 2 (SOD2, antioxidant against O{sub 2}{sup ?}) to decrease ROS level and investigated their role in the process of arsenic-induced cell transformation. Our results show that inhibition of ROS by antioxidant enzymes decreased arsenic-induced cell transformation, demonstrating that ROS are important in this process. We have also shown that in arsenic-transformed cells, ROS generation was lower and levels of antioxidants are higher than those in parent cells, in a disagreement with the previous report. The present study has also shown that the arsenic-transformed cells acquired apoptosis resistance. The inhibition of catalase to increase ROS level restored apoptosis capability of arsenic-transformed BEAS-2B cells, further showing that ROS levels are low in these cells. The apoptosis resistance due to the low ROS levels may increase cells proliferation, providing a favorable environment for tumorigenesis of arsenic-transformed cells.

  19. Early prediction of tumor recurrence based on CT texture changes after stereotactic ablative radiotherapy (SABR) for lung cancer

    SciTech Connect (OSTI)

    Mattonen, Sarah A.; Palma, David A.; Department of Oncology, The University of Western Ontario, London, Ontario N6A 4L6; Division of Radiation Oncology, London Regional Cancer Program, London, Ontario N6A 4L6 ; Haasbeek, Cornelis J. A.; Senan, Suresh; Ward, Aaron D.

    2014-03-15

    Purpose: Benign computed tomography (CT) changes due to radiation induced lung injury (RILI) are common following stereotactic ablative radiotherapy (SABR) and can be difficult to differentiate from tumor recurrence. The authors measured the ability of CT image texture analysis, compared to more traditional measures of response, to predict eventual cancer recurrence based on CT images acquired within 5 months of treatment. Methods: A total of 24 lesions from 22 patients treated with SABR were selected for this study: 13 with moderate to severe benign RILI, and 11 with recurrence. Three-dimensional (3D) consolidative and ground-glass opacity (GGO) changes were manually delineated on all follow-up CT scans. Two size measures of the consolidation regions (longest axial diameter and 3D volume) and nine appearance features of the GGO were calculated: 2 first-order features [mean density and standard deviation of density (first-order texture)], and 7 second-order texture features [energy, entropy, correlation, inverse difference moment (IDM), inertia, cluster shade, and cluster prominence]. For comparison, the corresponding response evaluation criteria in solid tumors measures were also taken for the consolidation regions. Prediction accuracy was determined using the area under the receiver operating characteristic curve (AUC) and two-fold cross validation (CV). Results: For this analysis, 46 diagnostic CT scans scheduled for approximately 3 and 6 months post-treatment were binned based on their recorded scan dates into 25 month and 58 month follow-up time ranges. At 25 months post-treatment, first-order texture, energy, and entropy provided AUCs of 0.790.81 using a linear classifier. On two-fold CV, first-order texture yielded 73% accuracy versus 76%77% with the second-order features. The size measures of the consolidative region, longest axial diameter and 3D volume, gave two-fold CV accuracies of 60% and 57%, and AUCs of 0.72 and 0.65, respectively. Conclusions: Texture measures of the GGO appearance following SABR demonstrated the ability to predict recurrence in individual patients within 5 months of SABR treatment. Appearance changes were also shown to be more accurately predictive of recurrence, as compared to size measures within the same time period. With further validation, these results could form the substrate for a clinically useful computer-aided diagnosis tool which could provide earlier salvage of patients with recurrence.

  20. Risk Factors for Brain Metastases in Locally Advanced Non-Small Cell Lung Cancer With Definitive Chest Radiation

    SciTech Connect (OSTI)

    Ji, Zhe; Bi, Nan; Wang, Jingbo; Hui, Zhouguang; Xiao, Zefen; Feng, Qinfu; Zhou, Zongmei; Chen, Dongfu; Lv, Jima; Liang, Jun; Fan, Chengcheng; Liu, Lipin; Wang, Luhua

    2014-06-01

    Purpose: We intended to identify risk factors that affect brain metastases (BM) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving definitive radiation therapy, which may guide the choice of selective prevention strategies. Methods and Materials: The characteristics of 346 patients with stage III NSCLC treated with thoracic radiation therapy from January 2008 to December 2010 in our institution were retrospectively reviewed. BM rates were analyzed by the Kaplan-Meier method. Multivariate Cox regression analysis was performed to determine independent risk factors for BM. Results: The median follow-up time was 48.3 months in surviving patients. A total of 74 patients (21.4%) experienced BM at the time of analysis, and for 40 (11.7%) of them, the brain was the first site of failure. The 1-year and 3-year brain metastasis rates were 15% and 28.1%, respectively. In univariate analysis, female sex, age ≤60 years, non-squamous cell carcinoma, T3-4, N3, >3 areas of lymph node metastasis, high lactate dehydrogenase and serum levels of tumor markers (CEA, NSE, CA125) before treatment were significantly associated with BM (P<.05). In multivariate analysis, age ≤60 years (P=.004, hazard ratio [HR] = 0.491), non-squamous cell carcinoma (P=.000, HR=3.726), NSE >18 ng/mL (P=.008, HR=1.968) and CA125 ≥ 35 U/mL (P=.002, HR=2.129) were independent risk factors for BM. For patients with 0, 1, 2, and 3 to 4 risk factors, the 3-year BM rates were 7.3%, 18.9%, 35.8%, and 70.3%, respectively (P<.001). Conclusions: Age ≤60 years, non-squamous cell carcinoma, serum NSE >18 ng/mL, and CA125 ≥ 35 U/mL were independent risk factors for brain metastasis. The possibilities of selectively using prophylactic cranial irradiation in higher-risk patients with LA-NSCLC should be further explored in the future.

  1. Predictors of Individual Tumor Local Control After Stereotactic Radiosurgery for Non-Small Cell Lung Cancer Brain Metastases

    SciTech Connect (OSTI)

    Garsa, Adam A.; Badiyan, Shahed N.; DeWees, Todd; Simpson, Joseph R.; Huang, Jiayi; Drzymala, Robert E.; Barani, Igor J.; Dowling, Joshua L.; Rich, Keith M.; Chicoine, Michael R.; Kim, Albert H.; Leuthardt, Eric C.; Robinson, Clifford G.

    2014-10-01

    Purpose: To evaluate local control rates and predictors of individual tumor local control for brain metastases from non-small cell lung cancer (NSCLC) treated with stereotactic radiosurgery (SRS). Methods and Materials: Between June 1998 and May 2011, 401 brain metastases in 228 patients were treated with Gamma Knife single-fraction SRS. Local failure was defined as an increase in lesion size after SRS. Local control was estimated using the Kaplan-Meier method. The Cox proportional hazards model was used for univariate and multivariate analysis. Receiver operating characteristic analysis was used to identify an optimal cutpoint for conformality index relative to local control. A P value <.05 was considered statistically significant. Results: Median age was 60 years (range, 27-84 years). There were 66 cerebellar metastases (16%) and 335 supratentorial metastases (84%). The median prescription dose was 20 Gy (range, 14-24 Gy). Median overall survival from time of SRS was 12.1 months. The estimated local control at 12 months was 74%. On multivariate analysis, cerebellar location (hazard ratio [HR] 1.94, P=.009), larger tumor volume (HR 1.09, P<.001), and lower conformality (HR 0.700, P=.044) were significant independent predictors of local failure. Conformality index cutpoints of 1.4-1.9 were predictive of local control, whereas a cutpoint of 1.75 was the most predictive (P=.001). The adjusted Kaplan-Meier 1-year local control for conformality index ≥1.75 was 84% versus 69% for conformality index <1.75, controlling for tumor volume and location. The 1-year adjusted local control for cerebellar lesions was 60%, compared with 77% for supratentorial lesions, controlling for tumor volume and conformality index. Conclusions: Cerebellar tumor location, lower conformality index, and larger tumor volume were significant independent predictors of local failure after SRS for brain metastases from NSCLC. These results warrant further investigation in a prospective setting.

  2. Stereotactic, Single-Dose Irradiation of Lung Tumors: A Comparison of Absolute Dose and Dose Distribution Between Pencil Beam and Monte Carlo Algorithms Based on Actual Patient CT Scans

    SciTech Connect (OSTI)

    Chen Huixiao; Lohr, Frank; Fritz, Peter; Wenz, Frederik; Dobler, Barbara; Lorenz, Friedlieb; Muehlnickel, Werner

    2010-11-01

    Purpose: Dose calculation based on pencil beam (PB) algorithms has its shortcomings predicting dose in tissue heterogeneities. The aim of this study was to compare dose distributions of clinically applied non-intensity-modulated radiotherapy 15-MV plans for stereotactic body radiotherapy between voxel Monte Carlo (XVMC) calculation and PB calculation for lung lesions. Methods and Materials: To validate XVMC, one treatment plan was verified in an inhomogeneous thorax phantom with EDR2 film (Eastman Kodak, Rochester, NY). Both measured and calculated (PB and XVMC) dose distributions were compared regarding profiles and isodoses. Then, 35 lung plans originally created for clinical treatment by PB calculation with the Eclipse planning system (Varian Medical Systems, Palo Alto, CA) were recalculated by XVMC (investigational implementation in PrecisePLAN [Elekta AB, Stockholm, Sweden]). Clinically relevant dose-volume parameters for target and lung tissue were compared and analyzed statistically. Results: The XVMC calculation agreed well with film measurements (<1% difference in lateral profile), whereas the deviation between PB calculation and film measurements was up to +15%. On analysis of 35 clinical cases, the mean dose, minimal dose and coverage dose value for 95% volume of gross tumor volume were 1.14 {+-} 1.72 Gy, 1.68 {+-} 1.47 Gy, and 1.24 {+-} 1.04 Gy lower by XVMC compared with PB, respectively (prescription dose, 30 Gy). The volume covered by the 9 Gy isodose of lung was 2.73% {+-} 3.12% higher when calculated by XVMC compared with PB. The largest differences were observed for small lesions circumferentially encompassed by lung tissue. Conclusions: Pencil beam dose calculation overestimates dose to the tumor and underestimates lung volumes exposed to a given dose consistently for 15-MV photons. The degree of difference between XVMC and PB is tumor size and location dependent. Therefore XVMC calculation is helpful to further optimize treatment planning.

  3. Poster Thur Eve 62: A Retrospective Assessment of the Prevalence and Dosimetric Effect of Lateral Electron Disequilibrium in a Population of Lung Cancer Patients Treated by Stereotactic Body Radiation Therapy

    SciTech Connect (OSTI)

    Disher, Brandon; Wade, Laura; Hajdok, George; Gaede, Stewart; Battista, Jerry J.; Palma, David

    2014-08-15

    Stereotactic Body Radiation Therapy (SBRT) is a treatment option for early stage non-small cell lung cancer (NSCLC). SBRT uses tightly conformed megavoltage (MV) x-ray beams to ablate the tumour. However, small MV x-ray fields may produce lateral electron disequilibrium (LED) within lung tissue, which can reduce the dose to tumour. The goal of this work is to estimate the prevalence of LED in NSCLC patients treated with SBRT, and determine dose effects for patients prone or averse to LED. Thirty NSCLC patients were randomly selected for analysis. 4-dimensional CT lung images were segmented into the right and left upper and lower lobes (RUL, RLL, LUL, LLL), and the right middle lobe. Dose calculations were performed using volume-modulated arc therapy in the Pinnacle{sup 3} TPS. Most tumours were located in the upper lobes (RUL 53%, LUL 27%) where density was significantly lower (RUL ?80846 HU vs. RLL ?74371 HU; LUL ?808 56 HU vs. LLL ?74670 HU; p<0.001). In general, the prevalence of LED increased with higher beam energy. Using 6MV photons, patients with a RUL tumour experienced moderate (81 %), and mild (19%) levels of LED. At 18MV, LED became more prominent with severe (50%) and moderate (50%) LED exhibited. Dosimetrically, for patients prone to LED, poorer target coverage (i.e. increased R100 by 20%) and improved lung sparing (i.e. reduced V20 by ?46%) was observed. The common location of lung cancers in the upper lobes, coupled with lower lung density, results in the potential occurrence of LED, which may underdose the tumour.

  4. Is Intermediate Radiation Dose Escalation With Concurrent Chemotherapy for Stage III NonSmall-Cell Lung Cancer Beneficial? A Multi-Institutional Propensity Score MatchedAnalysis

    SciTech Connect (OSTI)

    Rodrigues, George; Oberije, Cary; Senan, Suresh; Tsujino, Kayoko; Wiersma, Terry; Moreno-Jimenez, Marta; Kim, Tae Hyun; Marks, Lawrence B.; Rengan, Ramesh; De Petris, Luigi; Ramella, Sara; DeRuyck, Kim; De Dios, Nria Rodriguez; Warner, Andrew; Bradley, Jeffrey D.; Palma, David A.

    2015-01-01

    Purpose: The clinical benefits and risks of dose escalation (DE) for stage III nonsmall-cell lung cancer (NSCLC) remain uncertain despite the results from Radiation Therapy Oncology Group (RTOG) protocol 0617. There is significant heterogeneity of practice, with many clinicians prescribing intermediate dose levels between the 0617 study arms of 60 and 74Gy. This study investigated whether this strategy is associated with any survival benefits/risks by analyzing a large multi-institutional database. Methods and Materials: An individual patient database of stage III NSCLC patients treated with radical intent concurrent chemoradiation therapy was created (13 institutions, n=1274 patients). Patients were divided into 2 groups based on tumor Biological Effective Dose at 10 Gy (BED 10): those receiving standard dose (SD; n=552), consisting of 72Gy?BED 10?76.8Gy (eg 60-64Gy/30-32 fractions [fr]), and those receiving intermediate dose (ID; n=497), consisting of 76.8Gy64Gy/32 fr and <74Gy/37 fr), with lower-dose patients (n=225) excluded from consideration. Patients were then matched using propensity scores, leading to 2 matched groups of 196 patients. Outcomes were compared using various statistics including interquartile range (IQR), Kaplan-Meier curves, and adjusted Cox regression analysis. Results: Matched groups were found to be balanced except for N stage (more N3 disease in SD), median treatment year (SD in 2003; ID in 2007), platinum and taxane chemotherapy (SD in 28%; ID in 39%), and median follow-up (SD were 89months; ID were 40months). Median dose fractionation was 60Gy/30 fr in SD (BED 10 IQR: 72.0-75.5Gy) and 66Gy/33 fr (BED 10 IQR: 78.6-79.2Gy) in ID. Survival curves for SD and ID matched cohorts were statistically similar (P=.27); however, a nonstatistically significant trend toward better survival for ID was observed after 15months (median survival SD: 19.3months; ID: 21.0months). There was an increase in grades III to V lung toxicity associated with ID (13.0% vs 4.9%, respectively). Conclusions: No significant overall survival benefits were found with intermediate DE; however, more grade III or greater lung toxicity was observed. The separation of survival curves after 15months of follow-up suggests that a small overall survival improvement associated with intermediate DE cannot be excluded.

  5. SU-E-T-452: Impact of Respiratory Motion On Robustly-Optimized Intensity-Modulated Proton Therapy to Treat Lung Cancers

    SciTech Connect (OSTI)

    Liu, W; Schild, S; Bues, M [Mayo Clinic Arizona, Phoenix, AZ (United States); Liao, Z; Sahoo, N [MD Anderson Cancer Center, Houston, TX (United States); Park, P [Scottsdale, GA (United States); Li, H [M.D. Anderson Cancer Center, Houston, TX (United States); Li, Y [Varian Medical Systems, Houston, TX (United States); Li, X; Shen, J [Mayo Clinic Arizona, Phoenix, AA (United States); Anand, A [Mayo Clinic Arizona, Phoenix (United States); Dong, L [Scripps Proton Therapy Center, San Diego, CA (United States); Zhu, X; Mohan, R [UT MD Anderson Cancer Center, Houston, TX (United States)

    2014-06-01

    Purpose: We compared conventionally optimized intensity-modulated proton therapy (IMPT) treatment plans against the worst-case robustly optimized treatment plans for lung cancer. The comparison of the two IMPT optimization strategies focused on the resulting plans' ability to retain dose objectives under the influence of patient set-up, inherent proton range uncertainty, and dose perturbation caused by respiratory motion. Methods: For each of the 9 lung cancer cases two treatment plans were created accounting for treatment uncertainties in two different ways: the first used the conventional Method: delivery of prescribed dose to the planning target volume (PTV) that is geometrically expanded from the internal target volume (ITV). The second employed the worst-case robust optimization scheme that addressed set-up and range uncertainties through beamlet optimization. The plan optimality and plan robustness were calculated and compared. Furthermore, the effects on dose distributions of the changes in patient anatomy due to respiratory motion was investigated for both strategies by comparing the corresponding plan evaluation metrics at the end-inspiration and end-expiration phase and absolute differences between these phases. The mean plan evaluation metrics of the two groups were compared using two-sided paired t-tests. Results: Without respiratory motion considered, we affirmed that worst-case robust optimization is superior to PTV-based conventional optimization in terms of plan robustness and optimality. With respiratory motion considered, robust optimization still leads to more robust dose distributions to respiratory motion for targets and comparable or even better plan optimality [D95% ITV: 96.6% versus 96.1% (p=0.26), D5% - D95% ITV: 10.0% versus 12.3% (p=0.082), D1% spinal cord: 31.8% versus 36.5% (p =0.035)]. Conclusion: Worst-case robust optimization led to superior solutions for lung IMPT. Despite of the fact that robust optimization did not explicitly account for respiratory motion it produced motion-resistant treatment plans. However, further research is needed to incorporate respiratory motion into IMPT robust optimization.

  6. SU-E-T-131: Dosimetric Impact and Evaluation of Different Heterogenity Algorithm in Volumetric Modulated Arc Therapy Plan for Stereotactic Ablative Radiotherapy Lung Treatment with the Flattening Filter Free Beam

    SciTech Connect (OSTI)

    Chung, J; Kim, J; Lee, J; Kim, Y

    2014-06-01

    Purpose: The present study aimed to investigate the dosimetric impacts of the anisotropic analytic algorithm (AAA) and the Acuros XB (AXB) plan for lung stereotactic ablative radiation therapy using flattening filter-free (FFF) beam. We retrospectively analyzed 10 patients. Methods: We retrospectively analyzed 10 patients. The dosimetric parameters for the target and organs at risk (OARs) from the treatment plans calculated with these dose calculation algorithms were compared. The technical parameters, such as the computation times and the total monitor units (MUs), were also evaluated. Results: A comparison of DVHs from AXB and AAA showed that the AXB plan produced a high maximum PTV dose by average 4.40% with a statistical significance but slightly lower mean PTV dose by average 5.20% compared to the AAA plans. The maximum dose to the lung was slightly higher in the AXB compared to the AAA. For both algorithms, the values of V5, V10 and V20 for ipsilateral lung were higher in the AXB plan more than those of AAA. However, these parameters for contralateral lung were comparable. The differences of maximum dose for the spinal cord and heart were also small. The computation time of AXB was found fast with the relative difference of 13.7% than those of AAA. The average of monitor units (MUs) for all patients was higher in AXB plans than in the AAA plans. These results indicated that the difference between AXB and AAA are large in heterogeneous region with low density. Conclusion: The AXB provided the advantages such as the accuracy of calculations and the reduction of the computation time in lung stereotactic ablative radiotherapy (SABR) with using FFF beam, especially for VMAT planning. In dose calculation with the media of different density, therefore, the careful attention should be taken regarding the impacts of different heterogeneity correction algorithms. The authors report no conflicts of interest.

  7. Gelatin based on Power-gel.TM. as solders for Cr.sup.4+laser tissue welding and sealing of lung air leak and fistulas in organs

    DOE Patents [OSTI]

    Alfano, Robert R.; Tang, Jing; Evans, Jonathan M.; Ho, Peng Pei

    2006-04-25

    Laser tissue welding can be achieved using tunable Cr.sup.4+ lasers, semiconductor lasers and fiber lasers, where the weld strength follows the absorption spectrum of water. The use of gelatin and esterified gelatin as solders in conjunction with laser inducted tissue welding impart much stronger tensile and torque strengths than albumin solders. Selected NIR wavelength from the above lasers can improve welding and avoid thermal injury to tissue when used alone or with gelatin and esterified gelatin solders. These discoveries can be used to enhance laser tissue welding of tissues such as skin, mucous, bone, blood vessel, nerve, brain, liver, pancreas, spleen, kidney, lung, bronchus, respiratory track, urinary tract, gastrointestinal tract, or gynecologic tract and as a sealant for pulmonary air leaks and fistulas such as intestinal, rectal and urinary fistulas.

  8. Quantification of incidental mediastinal and hilar irradiation delivered during definitive stereotactic body radiation therapy for peripheral non-small cell lung cancer

    SciTech Connect (OSTI)

    Martin, Kate L.; Gomez, Jorge; Nazareth, Daryl P.; Warren, Graham W.; Singh, Anurag K.

    2012-07-01

    To determine the amount of incidental radiation dose received by the mediastinal and hilar nodes for patients with non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT). Fifty consecutive patients with NSCLC, treated using an SBRT technique, were identified. Of these patients, 38 had a prescription dose of 60 Gy in 20-Gy fractions and were eligible for analysis. For each patient, ipsilateral upper (level 2) and lower (level 4) paratracheal, and hilar (level 10) nodal regions were contoured on the planning computed tomography (CT) images. Using the clinical treatment plan, dose and volume calculations were performed retrospectively for each nodal region. SBRT to upper lobe tumors resulted in an average total ipsilateral mean dose of between 5.2 and 7.8 Gy for the most proximal paratracheal nodal stations (2R and 4R for right upper lobe lesions, 2L and 4L for left upper lobe lesions). SBRT to lower lobe tumors resulted in an average total ipsilateral mean dose of between 15.6 and 21.5 Gy for the most proximal hilar nodal stations (10R for right lower lobe lesions, 10 l for left lower lobe lesions). Doses to more distal nodes were substantially lower than 5 Gy. The often substantial incidental irradiation, delivered during SBRT for peripheral NSCLC of the lower lobes to the most proximal hilar lymph nodes may be therapeutic for low-volume, subclinical nodal disease. Treatment of peripheral upper lobe lung tumors delivers less incidental irradiation to the paratracheal lymph nodes with lower likelihood of therapeutic benefit.

  9. Clinically Meaningful Differences in Patient-Reported Outcomes With Amifostine in Combination With Chemoradiation for Locally Advanced Non-Small-Cell Lung Cancer: An Analysis of RTOG 9801

    SciTech Connect (OSTI)

    Sarna, Linda [University of California, Los Angeles, CA (United States)], E-mail: lsarna@sonnet.ucla.edu; Swann, Suzanne [Radiation Therapy Oncology Group, Philadelphia, PA (United States); Langer, Corey [Fox Chase Cancer Center, Philadelphia, PA (United States); Werner-Wasik, Maria [Thomas Jefferson University, Jefferson Medical College, Philadelphia, PA (United States); Nicolaou, Nicos [Fox Chase Cancer Center, Philadelphia, PA (United States); Komaki, Ritsuko [M.D. Anderson Cancer Center, Houston, TX (United States); Machtay, Mitchell [Thomas Jefferson University, Jefferson Medical College, Philadelphia, PA (United States); Byhardt, Roger [Medical College of Wisconsin, Milwaukee, WI (United States); Wasserman, Todd [Washington University, St. Louis, MO (United States); Movsas, Benjamin [Henry Ford Health System, Detroit, MI (United States)

    2008-12-01

    Purpose: The purpose of this study is to analyze changes in quality of life (QOL) and symptoms from pretreatment to 6 weeks posttreatment in a Phase III randomized study (Radiation Therapy Oncology Group 9801) of amifostine (AM) vs. no AM in patients with Stages II-III non-small-cell lung cancer receiving paclitaxel and carboplatin as induction and then concurrently with hyperfractionated radiation therapy (RT). Methods and Materials: One hundred thirty-eight patients with baseline and 6-week posttreatment QOL data were analyzed. There were no significant differences in baseline demographics between those who did and did not have QOL data. The QOL and symptoms were assessed by using the European Organization for Research and Treatment of Cancer (EORTC) Global QOL and Pain subscales and the EORTC-Lung Cancer-13 symptom tool. Clinically relevant changes in QOL were characterized by 10-point differences in individual scores pre/post treatment. A daily diary of patient-rated difficulty swallowing and a weekly physician-rated dysphagia log (using National Cancer Institute Common Toxicity Criteria) were completed during treatment. Weight loss was monitored. Differences in outcomes were examined according to smoking status, alcohol use, and sex. Results: Patients receiving AM reported significantly greater pain reduction after chemoradiation (34% vs. no AM, 21%), less difficulty swallowing during chemoradiation, and less weight loss than patients not receiving AM. However, physician-rated assessments of dysphagia were not significantly different by treatment arm. There were no other significant changes in QOL or symptoms according to treatment arm, smoking status, alcohol use, or sex. Conclusions: Patient evaluations of difficulty swallowing and pain suggest benefits from AM use that are distinct from clinician-rated assessments.

  10. Stereotactic Body Radiotherapy Versus Surgery for Medically Operable Stage I Non-Small-Cell Lung Cancer: A Markov Model-Based Decision Analysis

    SciTech Connect (OSTI)

    Louie, Alexander V.; Rodrigues, George; Palma, David A.; Cao, Jeffrey Q.; Yaremko, Brian P.; Malthaner, Richard; Mocanu, Joseph D.

    2011-11-15

    Purpose: To compare the quality-adjusted life expectancy and overall survival in patients with Stage I non-small-cell lung cancer (NSCLC) treated with either stereotactic body radiation therapy (SBRT) or surgery. Methods and Materials: We constructed a Markov model to describe health states after either SBRT or lobectomy for Stage I NSCLC for a 5-year time frame. We report various treatment strategy survival outcomes stratified by age, sex, and pack-year history of smoking, and compared these with an external outcome prediction tool (Adjuvant{exclamation_point} Online). Results: Overall survival, cancer-specific survival, and other causes of death as predicted by our model correlated closely with those predicted by the external prediction tool. Overall survival at 5 years as predicted by baseline analysis of our model is in favor of surgery, with a benefit ranging from 2.2% to 3.0% for all cohorts. Mean quality-adjusted life expectancy ranged from 3.28 to 3.78 years after surgery and from 3.35 to 3.87 years for SBRT. The utility threshold for preferring SBRT over surgery was 0.90. Outcomes were sensitive to quality of life, the proportion of local and regional recurrences treated with standard vs. palliative treatments, and the surgery- and SBRT-related mortalities. Conclusions: The role of SBRT in the medically operable patient is yet to be defined. Our model indicates that SBRT may offer comparable overall survival and quality-adjusted life expectancy as compared with surgical resection. Well-powered prospective studies comparing surgery vs. SBRT in early-stage lung cancer are warranted to further investigate the relative survival, quality of life, and cost characteristics of both treatment paradigms.

  11. Predictive Treatment Management: Incorporating a Predictive Tumor Response Model Into Robust Prospective Treatment Planning for Non-Small Cell Lung Cancer

    SciTech Connect (OSTI)

    Zhang, Pengpeng; Yorke, Ellen; Hu, Yu-Chi; Mageras, Gig; Rimner, Andreas; Deasy, Joseph O.

    2014-02-01

    Purpose: We hypothesized that a treatment planning technique that incorporates predicted lung tumor regression into optimization, predictive treatment planning (PTP), could allow dose escalation to the residual tumor while maintaining coverage of the initial target without increasing dose to surrounding organs at risk (OARs). Methods and Materials: We created a model to estimate the geometric presence of residual tumors after radiation therapy using planning computed tomography (CT) and weekly cone beam CT scans of 5 lung cancer patients. For planning purposes, we modeled the dynamic process of tumor shrinkage by morphing the original planning target volume (PTV{sub orig}) in 3 equispaced steps to the predicted residue (PTV{sub pred}). Patients were treated with a uniform prescription dose to PTV{sub orig}. By contrast, PTP optimization started with the same prescription dose to PTV{sub orig} but linearly increased the dose at each step, until reaching the highest dose achievable to PTV{sub pred} consistent with OAR limits. This method is compared with midcourse adaptive replanning. Results: Initial parenchymal gross tumor volume (GTV) ranged from 3.6 to 186.5 cm{sup 3}. On average, the primary GTV and PTV decreased by 39% and 27%, respectively, at the end of treatment. The PTP approach gave PTV{sub orig} at least the prescription dose, and it increased the mean dose of the true residual tumor by an average of 6.0 Gy above the adaptive approach. Conclusions: PTP, incorporating a tumor regression model from the start, represents a new approach to increase tumor dose without increasing toxicities, and reduce clinical workload compared with the adaptive approach, although model verification using per-patient midcourse imaging would be prudent.

  12. MAINE MULTIFAMILY BUILDING OWNERS TRUST IN EFFICIENCY | Department...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    ... marketing efforts by building relationships with statewide landlord associations, holding additional community events, providing webinars for building owners, and expanding online ...

  13. Cyberspace Policy Review: Assuring a Trusted and Resilient Information...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    The review team of government cybersecurity experts engaged and received input from a broad cross-section of industry, academia, the civil liberties and privacy communities, State ...

  14. Multi Platform Trusted Copy (MPTC) V 5.0

    Energy Science and Technology Software Center (OSTI)

    2005-03-01

    MPTC 5.0 reviews text files; Microsoft (MS) Word, PowerPoint, and Excel in the MS Office 2000, XP, and 2003 formats; MS Access in the XP and 2003 formats; and dxf CAD files for keywords supplied by the reviewer. Keywords are specified in a keyword file or entered via the GUI at review time so that each document review can be customized. In addition, MPTC detects embedded objects and removes Microsoft-documented metadata from the supported MSmore » Office file formats. After each review, a user can examine the review log for MPTC's findings. A file can be opened with its creating application from within MPTC for visual review and resolution of review failures. If MPTC pases the file file or the reviewer has resolved review failures, the reviewer can transfer the file to an unclassified, removable medium with the following caveats: MPTC prohibits the transfer of any file containing a hidden data stream. Compressed files and file archives cannot be transferred without first uncompressing or extracting the files. MPTC provides a detection mechanism for Java-based intelligent agents and rudimentary steganography detection capability. MPTC ensures that only the designated files are copied, moved, or deleted and confirms each operation after completion. MPTC records all transactions and user logon identities in encrypted review, transfer, and session log files. MPTC compiles with the DOE/NNSA two-person rule by requiring that the names of two reviewers be enetered prior to file transfer. The MPTC code is designed to accommodate additional review tools to enhance the effectiveness of the Authorized Derivative Classifier (ADC) or other authorized user and reduce the security risks associated with file transfers. Cross-plaform: Runs on Windows 2000, Windows XP, Red Hat Enterprise Linux Workstation, Fedora Core 2 and 3, Red Hat Linux 9, Solaris 8, and Solaris 9.« less

  15. Trusted materials using orthogonal testing. 2015 Annual report

    SciTech Connect (OSTI)

    Van Benthem, Mark

    2015-09-01

    The purpose of this project is to prove (or disprove) that a reasonable number of simple tests can be used to provide a unique data signature for materials, changes in which could serve as a harbinger of material deviation, prompting further evaluations. The routine tests are mutually orthogonal to any currently required materials specification tests.

  16. Meridian Trust Wind Farm II | Open Energy Information

    Open Energy Info (EERE)

    Energy Resources Developer Kenetech Windpower Energy Purchaser Southern California Edison Co Location San Gorgonio CA Coordinates 33.9095, -116.734 Show Map Loading map......

  17. Section 28 Trust Wind Farm | Open Energy Information

    Open Energy Info (EERE)

    Commercial Scale Wind Facility Status In Service Energy Purchaser Southern California Edison Co Location San Gorgonio CA Coordinates 33.9095, -116.734 Show Map Loading map......

  18. Meridian Trust Wind Farm I | Open Energy Information

    Open Energy Info (EERE)

    Energy Resources Developer Kenetech Windpower Energy Purchaser Southern California Edison Co Location San Gorgonio CA Coordinates 33.9095, -116.734 Show Map Loading map......

  19. Declaration of Trust 5.13.2013.pdf

    Energy Savers [EERE]

  20. Energy Trust of Oregon Inc | Open Energy Information

    Open Energy Info (EERE)

    Product: Gives grants for the implementation of efficiency improvements and renewable energy sources at a household and utility-scale level. Coordinates: 45.511795,...

  1. Efficiency Maine Trust - Energy Efficiency and Renewable Resource...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    their electric bill. Every six months, each utility must notify its customers of the existence and purpose of the fund, the means to contribute to the fund, and summaries of...

  2. Cyberspace Policy Review: Assuring a Trusted and Resilient Information...

    Energy Savers [EERE]

    new security innovation, and secure managed services. 38 appendix a: bibliography Accenture, "Secure Enterprise Network Consortium: Helping Provide Comprehensive Cyber Security...

  3. Black Pine Engineering Wins Clean Energy Trust Clean Energy Challenge...

    Office of Environmental Management (EM)

    ... Round Axiom Exergy's Refrigeration BatteryTM technology reduces the electricity load of a typical supermarket by shifting the bulk of refrigeration-related energy usage ...

  4. National Trust for Historic Preservation: America Saves! Energizing...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Energy Center of Wisconsin - Madison, WI - EnerPath - Rochester, NY - Ecology Action - Santa Cruz, CA - Community Power Works - Seattle, WA DOE Total Funding: 1,600,000 Cost...

  5. Sandia National Laboratories: Rad-Hard Electronics and Trusted...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    testing of electronic microsystems for both unclassified and classified integrated circuits. Application-Specific Integrated Circuits (ASICs) Sandia's Application-Specific...

  6. Black Pine Engineering Wins Clean Energy Trust Clean Energy Challenge

    Broader source: Energy.gov [DOE]

    Student team from Michigan State University takes top honors at the Eastern Midwest regional competition of the Energy Department’s National Clean Energy Business Plan Competition for its advanced turbomachinery system for geothermal power plants.

  7. Can We Trust GRB High Energy Correlations? (Journal Article)...

    Office of Scientific and Technical Information (OSTI)

    We show that several GRB correlations have common features indicative of an origin in selection effects. We focus on the possible origin of the Esub pk-Esub iso correlation in ...

  8. The effect of irregular breathing patterns on internal target volumes in four-dimensional CT and cone-beam CT images in the context of stereotactic lung radiotherapy

    SciTech Connect (OSTI)

    Clements, N.; Kron, T.; Roxby, P.; Franich, R.; Dunn, L.; Aarons, Y.; Chesson, B.; Siva, S.; Duplan, D.; Ball, D.

    2013-02-15

    Purpose: Stereotactic lung radiotherapy is complicated by tumor motion from patient respiration. Four-dimensional CT (4DCT) imaging is a motion compensation method used in treatment planning to generate a maximum intensity projection (MIP) internal target volume (ITV). Image guided radiotherapy during treatment may involve acquiring a volumetric cone-beam CT (CBCT) image and visually aligning the tumor to the planning 4DCT MIP ITV contour. Moving targets imaged with CBCT can appear blurred and currently there are no studies reporting on the effect that irregular breathing patterns have on CBCT volumes and their alignment to 4DCT MIP ITV contours. The objective of this work was therefore to image a phantom moving with irregular breathing patterns to determine whether any configurations resulted in errors in volume contouring or alignment. Methods: A Perspex thorax phantom was used to simulate a patient. Three wooden 'lung' inserts with embedded Perspex 'lesions' were moved up to 4 cm with computer-generated motion patterns, and up to 1 cm with patient-specific breathing patterns. The phantom was imaged on 4DCT and CBCT with the same acquisition settings used for stereotactic lung patients in the clinic and the volumes on all phantom images were contoured. This project assessed the volumes for qualitative and quantitative changes including volume, length of the volume, and errors in alignment between CBCT volumes and 4DCT MIP ITV contours. Results: When motion was introduced 4DCT and CBCT volumes were reduced by up to 20% and 30% and shortened by up to 7 and 11 mm, respectively, indicating that volume was being under-represented at the extremes of motion. Banding artifacts were present in 4DCT MIP images, while CBCT volumes were largely reduced in contrast. When variable amplitudes from patient traces were used and CBCT ITVs were compared to 4DCT MIP ITVs there was a distinct trend in reduced ITV with increasing amplitude that was not seen when compared to true ITVs. Breathing patterns with a rest period following expiration resulted in well-defined superior edges and were better aligned using an edge-to-edge alignment technique. In most cases, sinusoidal motion patterns resulted in the closest agreements to true values and the smallest misalignments. Conclusions: Strategies are needed to compensate for volume losses at the extremes of motion for both 4DCT MIP and CBCT images for larger and varied amplitudes, and for patterns with rest periods following expiration. Lesions moving greater than 2 cm would warrant larger treatment margins added to the 4DCT MIP ITV to account for the volume being under-represented at the extremes of motion. Lesions moving with a rest period following expiration would be better aligned using an edge-to-edge alignment technique. Sinusoidal patterns represented the ideal clinical scenario, reinforcing the importance of investigating clinically relevant motions and their effects on 4DCT MIP and CBCT volumes. Since most patients do not breathe sinusoidally this may lead to misinterpretation of previous studies using only sinusoidal motion.

  9. TU-F-17A-08: The Relative Accuracy of 4D Dose Accumulation for Lung Radiotherapy Using Rigid Dose Projection Versus Dose Recalculation On Every Breathing Phase

    SciTech Connect (OSTI)

    Lamb, J; Lee, C; Tee, S; Lee, P; Iwamoto, K; Low, D; Valdes, G; Robinson, C

    2014-06-15

    Purpose: To investigate the accuracy of 4D dose accumulation using projection of dose calculated on the end-exhalation, mid-ventilation, or average intensity breathing phase CT scan, versus dose accumulation performed using full Monte Carlo dose recalculation on every breathing phase. Methods: Radiotherapy plans were analyzed for 10 patients with stage I-II lung cancer planned using 4D-CT. SBRT plans were optimized using the dose calculated by a commercially-available Monte Carlo algorithm on the end-exhalation 4D-CT phase. 4D dose accumulations using deformable registration were performed with a commercially available tool that projected the planned dose onto every breathing phase without recalculation, as well as with a Monte Carlo recalculation of the dose on all breathing phases. The 3D planned dose (3D-EX), the 3D dose calculated on the average intensity image (3D-AVE), and the 4D accumulations of the dose calculated on the end-exhalation phase CT (4D-PR-EX), the mid-ventilation phase CT (4D-PR-MID), and the average intensity image (4D-PR-AVE), respectively, were compared against the accumulation of the Monte Carlo dose recalculated on every phase. Plan evaluation metrics relating to target volumes and critical structures relevant for lung SBRT were analyzed. Results: Plan evaluation metrics tabulated using 4D-PR-EX, 4D-PR-MID, and 4D-PR-AVE differed from those tabulated using Monte Carlo recalculation on every phase by an average of 0.140.70 Gy, - 0.110.51 Gy, and 0.000.62 Gy, respectively. Deviations of between 8 and 13 Gy were observed between the 4D-MC calculations and both 3D methods for the proximal bronchial trees of 3 patients. Conclusions: 4D dose accumulation using projection without re-calculation may be sufficiently accurate compared to 4D dose accumulated from Monte Carlo recalculation on every phase, depending on institutional protocols. Use of 4D dose accumulation should be considered when evaluating normal tissue complication probabilities as well as in clinical situations where target volumes are directly inferior to mobile critical structures.

  10. Radiosensitizing Effects of Ectopic miR-101 on Non-Small-Cell Lung Cancer Cells Depend on the Endogenous miR-101 Level

    SciTech Connect (OSTI)

    Chen, Susie; Wang Hongyan; Ng, Wooi Loon; Curran, Walter J.; Wang Ya

    2011-12-01

    Purpose: Previously, we showed that ectopic miR-101 could sensitize human tumor cells to radiation by targeting ATM and DNA-PK catalytic subunit (DNA-PKcs) to inhibit DNA repair, as the endogenous miR-101 levels are low in tumors in general. However, the heterogeneity of human cancers may result in an exception. The purpose of this study was to test the hypothesis that a few tumor cell lines with a high level of endogenous miR-101 would prove less response to ectopic miR-101. Methods and Materials: Fourteeen non-small-cell lung cancer (NSCLC) cell lines and one immortalized non-malignant lung epithelial cell line (NL20) were used for comparing endogenous miR-101 levels by real-time reverse transcription-polymerase chain reaction. Based on the different miR-101 levels, four cell lines with different miR-101 levels were chosen for transfection with a green fluorescent protein-lentiviral plasmid encoding miR-101. The target protein levels were measured by using Western blotting. The radiosensitizing effects of ectopic miR-101 on these NSCLC cell lines were determined by a clonogenic assay and xenograft mouse model. Results: The endogenous miR-101 level was similar or lower in 13 NSCLC cell lines but was 11-fold higher in one cell line (H157) than in NL20 cells. Although ectopic miR-101 efficiently decreased the ATM and DNA-PKcs levels and increased the radiosensitization level in H1299, H1975, and A549 cells, it did not change the levels of the miR-101 targets or radiosensitivity in H157 cells. Similar results were observed in xenograft mice. Conclusions: A small number of NSCLC cell lines could have a high level of endogenous miR-101. The ectopic miR-101 was able to radiosensitize most NSCLC cells, except for the NSCLC cell lines that had a much higher endogenous miR-101 level. These results suggest that when we choose one miRNA as a therapeutic tool, the endogenous level of the miRNA in each tumor should be considered.

  11. Effects of Respiratory Motion on Passively Scattered Proton Therapy Versus Intensity Modulated Photon Therapy for Stage III Lung Cancer: Are Proton Plans More Sensitive to Breathing Motion?

    SciTech Connect (OSTI)

    Matney, Jason; Park, Peter C. [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); The University of Texas Graduate School of Biomedical Sciences, Houston, Texas (United States); Bluett, Jaques [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Chen, Yi Pei [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); The University of Texas Graduate School of Biomedical Sciences, Houston, Texas (United States); Liu, Wei; Court, Laurence E. [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liao, Zhongxing [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Li, Heng [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mohan, Radhe, E-mail: rmohan@mdanderson.org [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-11-01

    Purpose: To quantify and compare the effects of respiratory motion on paired passively scattered proton therapy (PSPT) and intensity modulated photon therapy (IMRT) plans; and to establish the relationship between the magnitude of tumor motion and the respiratory-induced dose difference for both modalities. Methods and Materials: In a randomized clinical trial comparing PSPT and IMRT, radiation therapy plans have been designed according to common planning protocols. Four-dimensional (4D) dose was computed for PSPT and IMRT plans for a patient cohort with respiratory motion ranging from 3 to 17 mm. Image registration and dose accumulation were performed using grayscale-based deformable image registration algorithms. The dosevolume histogram (DVH) differences (4D-3D [3D = 3-dimensional]) were compared for PSPT and IMRT. Changes in 4D-3D dose were correlated to the magnitude of tumor respiratory motion. Results: The average 4D-3D dose to 95% of the internal target volume was close to zero, with 19 of 20 patients within 1% of prescribed dose for both modalities. The mean 4D-3D between the 2 modalities was not statistically significant (P<.05) for all dosevolume histogram indices (mean SD) except the lung V5 (PSPT: +1.1% 0.9%; IMRT: +0.4% 1.2%) and maximum cord dose (PSPT: +1.5 2.9 Gy; IMRT: 0.0 0.2 Gy). Changes in 4D-3D dose were correlated to tumor motion for only 2 indices: dose to 95% planning target volume, and heterogeneity index. Conclusions: With our current margin formalisms, target coverage was maintained in the presence of respiratory motion up to 17 mm for both PSPT and IMRT. Only 2 of 11 4D-3D indices (lung V5 and spinal cord maximum) were statistically distinguishable between PSPT and IMRT, contrary to the notion that proton therapy will be more susceptible to respiratory motion. Because of the lack of strong correlations with 4D-3D dose differences in PSPT and IMRT, the extent of tumor motion was not an adequate predictor of potential dosimetric error caused by breathing motion.

  12. Do Angiotensin-Converting Enzyme Inhibitors Reduce the Risk of Symptomatic Radiation Pneumonitis in Patients With Non-Small Cell Lung Cancer After Definitive Radiation Therapy? Analysis of a Single-Institution Database

    SciTech Connect (OSTI)

    Wang, Hongmei [Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, P.R. of China (China); Liao, Zhongxing, E-mail: zliao@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Zhuang, Yan; Xu, Ting; Nguyen, Quynh-Nhu; Levy, Lawrence B.; O'Reilly, Michael [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gold, Kathryn A. [Department of Thoracic Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gomez, Daniel R. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-12-01

    Purpose: Preclinical studies have suggested that angiotensin-converting enzyme inhibitors (ACEIs) can mitigate radiation-induced lung injury. We sought here to investigate possible associations between ACEI use and the risk of symptomatic radiation pneumonitis (RP) among patients undergoing radiation therapy (RT) for nonsmall cell lung cancer (NSCLC). Methods and Materials: We retrospectively identified patients who received definitive radiation therapy for stages I to III NSCLC between 2004 and 2010 at a single tertiary cancer center. Patients must have received a radiation dose of at least 60 Gy for a single primary lung tumor and have had imaging and dosimetric data available for analysis. RP was quantified according to Common Terminology Criteria for Adverse Events, version 3.0. A Cox proportional hazard model was used to assess potential associations between ACEI use and risk of symptomatic RP. Results: Of 413 patients analyzed, 65 were using ACEIs during RT. In univariate analysis, the rate of RP grade ?2 seemed lower in ACEI users than in nonusers (34% vs 46%), but this apparent difference was not statistically significant (P=.06). In multivariate analysis of all patients, ACEI use was not associated with the risk of symptomatic RP (hazard ratio [HR] = 0.66; P=.07) after adjustment for sex, smoking status, mean lung dose (MLD), and concurrent carboplatin and paclitaxel chemotherapy. Subgroup analysis showed that ACEI use did have a protective effect from RP grade ?2 among patients who received a low (?20-Gy) MLD (P<.01) or were male (P=.04). Conclusions: A trend toward reduction in symptomatic RP among patients taking ACEIs during RT for NSCLC was not statistically significant on univariate or multivariate analyses, although certain subgroups may benefit from use (ie, male patients and those receiving low MLD). The evidence at this point is insufficient to establish whether the use of ACEIs does or does not reduce the risk of RP.

  13. Prognostic Impact of Radiation Therapy to the Primary Tumor in Patients With Non-small Cell Lung Cancer and Oligometastasis at Diagnosis

    SciTech Connect (OSTI)

    Lopez Guerra, Jose Luis [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States) [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Radiation Oncology, Instituto Madrileno de Oncologia/Grupo IMO, Madrid (Spain); Gomez, Daniel, E-mail: dgomez@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Zhuang, Yan; Hong, David S. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Heymach, John V. [Department of Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Swisher, Stephen G. [Department of Thoracic Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Thoracic Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lin, Steven H.; Komaki, Ritsuko; Cox, James D.; Liao Zhongxing [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2012-09-01

    Purpose: We investigated prognostic factors associated with survival in patients with non-small cell lung cancer (NSCLC) and oligometastatic disease at diagnosis, particularly the influence of local treatment to the primary site on prognosis. Methods and Materials: From January 2000 through June 2011, 78 consecutive patients with oligometastatic NSCLC (<5 metastases) at diagnosis underwent definitive chemoradiation therapy ({>=}45 Gy) to the primary site. Forty-four of these patients also received definitive local treatment for the oligometastases. Survival outcomes were estimated using the Kaplan-Meier method, and risk factors were identified by univariate and multivariate analyses. Results: Univariate Cox proportional hazard analysis revealed better overall survival (OS) for those patients who received at least 63 Gy of radiation to the primary site (P=.002), received definitive local treatment for oligometastasis (P=.041), had a Karnofsky performance status (KPS) score >80 (P=.007), had a gross tumor volume {<=}124 cm{sup 3} (P=.002), had adenocarcinoma histology (P=.002), or had no history of respiratory disease (P=.016). On multivariate analysis, radiation dose, performance status, and tumor volume retained significance (P=.004, P=.006, and P<.001, respectively). The radiation dose also maintained significance when patients with and without brain metastases were analyzed separately. Conclusions: Tumor volume, KPS, and receipt of at least 63 Gy to the primary tumor are associated with improved OS in patients with oligometastatic NSCLC at diagnosis. Our results suggest that a subset of such patients may benefit from definitive local therapy.

  14. SU-E-T-481: Dosimetric Comparison of Acuros XB and Anisotropic Analytic Algorithm with Commercial Monte Carlo Based Dose Calculation Algorithm for Stereotactic Body Radiation Therapy of Lung Cancer

    SciTech Connect (OSTI)

    Cao, M; Tenn, S; Lee, C; Yang, Y; Lamb, J; Agazaryan, N; Lee, P; Low, D

    2014-06-01

    Purpose: To evaluate performance of three commercially available treatment planning systems for stereotactic body radiation therapy (SBRT) of lung cancer using the following algorithms: Boltzmann transport equation based algorithm (AcurosXB AXB), convolution based algorithm Anisotropic Analytic Algorithm (AAA); and Monte Carlo based algorithm (XVMC). Methods: A total of 10 patients with early stage non-small cell peripheral lung cancer were included. The initial clinical plans were generated using the XVMC based treatment planning system with a prescription of 54Gy in 3 fractions following RTOG0613 protocol. The plans were recalculated with the same beam parameters and monitor units using AAA and AXB algorithms. A calculation grid size of 2mm was used for all algorithms. The dose distribution, conformity, and dosimetric parameters for the targets and organs at risk (OAR) are compared between the algorithms. Results: The average PTV volume was 19.6mL (range 4.247.2mL). The volume of PTV covered by the prescribed dose (PTV-V100) were 93.972.00%, 95.072.07% and 95.102.97% for XVMC, AXB and AAA algorithms, respectively. There was no significant difference in high dose conformity index; however, XVMC predicted slightly higher values (p=0.04) for the ratio of 50% prescription isodose volume to PTV (R50%). The percentage volume of total lungs receiving dose >20Gy (LungV20Gy) were 4.032.26%, 3.862.22% and 3.852.21% for XVMC, AXB and AAA algorithms. Examination of dose volume histograms (DVH) revealed small differences in targets and OARs for most patients. However, the AAA algorithm was found to predict considerable higher PTV coverage compared with AXB and XVMC algorithms in two cases. The dose difference was found to be primarily located at the periphery region of the target. Conclusion: For clinical SBRT lung treatment planning, the dosimetric differences between three commercially available algorithms are generally small except at target periphery. XVMC and AXB algorithms are recommended for accurate dose estimation at tissue boundaries.

  15. AZD5438, an Inhibitor of Cdk1, 2, and 9, Enhances the Radiosensitivity of Non-Small Cell Lung Carcinoma Cells

    SciTech Connect (OSTI)

    Raghavan, Pavithra; Tumati, Vasu; Yu Lan; Chan, Norman; Tomimatsu, Nozomi; Burma, Sandeep; Simmons Comprehensive Cancer Center, Dallas, Texas ; Bristow, Robert G.; Saha, Debabrata; Simmons Comprehensive Cancer Center, Dallas, Texas

    2012-11-15

    Purpose: Radiation therapy (RT) is one of the primary modalities for treatment of non-small cell lung cancer (NSCLC). However, due to the intrinsic radiation resistance of these tumors, many patients experience RT failure, which leads to considerable tumor progression including regional lymph node and distant metastasis. This preclinical study evaluated the efficacy of a new-generation cyclin-dependent kinase (Cdk) inhibitor, AZD5438, as a radiosensitizer in several NSCLC models that are specifically resistant to conventional fractionated RT. Methods and Materials: The combined effect of ionizing radiation and AZD5438, a highly specific inhibitor of Cdk1, 2, and 9, was determined in vitro by surviving fraction, cell cycle distribution, apoptosis, DNA double-strand break (DSB) repair, and homologous recombination (HR) assays in 3 NSCLC cell lines (A549, H1299, and H460). For in vivo studies, human xenograft animal models in athymic nude mice were used. Results: Treatment of NSCLC cells with AZD5438 significantly augmented cellular radiosensitivity (dose enhancement ratio rangeing from 1.4 to 1.75). The degree of radiosensitization by AZD5438 was greater in radioresistant cell lines (A549 and H1299). Radiosensitivity was enhanced specifically through inhibition of Cdk1, prolonged G{sub 2}-M arrest, inhibition of HR, delayed DNA DSB repair, and increased apoptosis. Combined treatment with AZD5438 and irradiation also enhanced tumor growth delay, with an enhancement factor ranging from 1.2-1.7. Conclusions: This study supports the evaluation of newer generation Cdk inhibitors, such as AZD5438, as potent radiosensitizers in NSCLC models, especially in tumors that demonstrate variable intrinsic radiation responses.

  16. Impact of Weight Change During the Course of Concurrent Chemoradiation Therapy on Outcomes in Stage IIIB Non-Small Cell Lung Cancer Patients: Retrospective Analysis of 425 Patients

    SciTech Connect (OSTI)

    Topkan, Erkan; Parlak, Cem; Selek, Ugur

    2013-11-15

    Purpose: We retrospectively investigated the impact of weight change (WC) during concurrent chemoradiation therapy (C-CRT) on clinical outcomes of stage 3B non-small cell lung cancer (NSCLC) patients. Methods and Materials: A total of 425 patients treated with C-CRT were included. All patients received 60 to 66 Gy of thoracic radiation therapy concurrently with 1 to 3 cycles of platinum-based chemotherapy. Pre- and posttreatment weight measurements on first and last days of C-CRT were used for WC. Patients were divided into 2 groups: group 1 = weight loss (WL); group 2 = weight preservation/gain (WP) for comparative analyses. Results: Following C-CRT, 252 patients (59.3%) experienced WL, while 89 patients (20.9%) and 84 patients (19.8%) showed WP or WG. At median 24.2 months of follow-up, 142 patients (33.4%) were alive (84 WP [48.6%] and 58 WL [23.0%]), and 58 (13.6%) of them were free of disease progression (41 [23.7%] for WP and 17 [6.7%] for WL). Median overall survival (OS), locoregional progression-free survival (LRPFS), progression-free survival (PFS), and distant metastases-free survival (DMFS) for the entire population were 22.8, 14.4, 10.6, and 11.7 months, respectively. Intergroup comparisons between WP and WL cohorts revealed significantly superior OS, LRPFS, PFS, and DMFS in WP patients (P<.05 for each). On multivariate analyses, only WL and advanced T stage were associated with poor prognosis (P<.05). Conclusions: Present results in 425 stage 3B NSCLC patients demonstrated that WL during C-CRT is strongly associated with inferior survival outcomes compared to WP. This emerging finding might be useful by forming an encouraging basis for future investigations in facilitating a way to improve the outcomes of these patients experiencing WL during C-CRT.

  17. Gamma Knife Stereotactic Radiosurgery as Salvage Therapy After Failure of Whole-Brain Radiotherapy in Patients With Small-Cell Lung Cancer

    SciTech Connect (OSTI)

    Harris, Sunit; Chan, Michael D.; Lovato, James F.; Ellis, Thomas L.; Tatter, Stephen B.; Bourland, J. Daniel; Munley, Michael T.; Guzman, Allan F. de; Shaw, Edward G.; Urbanic, James J.; McMullen, Kevin P.

    2012-05-01

    Purpose: Radiosurgery has been successfully used in selected cases to avoid repeat whole-brain irradiation (WBI) in patients with multiple brain metastases of most solid tumor histological findings. Few data are available for the use of radiosurgery for small-cell lung cancer (SCLC). Methods and Materials: Between November 1999 and June 2009, 51 patients with SCLC and previous WBI and new brain metastases were treated with GammaKnife stereotactic radiosurgery (GKSRS). A median dose of 18 Gy (range, 10-24 Gy) was prescribed to the margin of each metastasis. Patients were followed with serial imaging. Patient electronic records were reviewed to determine disease-related factors and clinical outcomes after GKSRS. Local and distant brain failure rates, overall survival, and likelihood of neurologic death were determined based on imaging results. The Kaplan-Meier method was used to determine survival and local and distant brain control. Cox proportional hazard regression was performed to determine strength of association between disease-related factors and survival. Results: Median survival time for the entire cohort was 5.9 months. Local control rates at 1 and 2 years were 57% and 34%, respectively. Distant brain failure rates at 1 and 2 years were 58% and 75%, respectively. Fifty-three percent of patients ultimately died of neurologic death. On multivariate analysis, patients with stable (hazard ratio [HR] = 2.89) or progressive (HR = 6.98) extracranial disease (ECD) had worse overall survival than patients without evidence of ECD (p = 0.00002). Concurrent chemotherapy improved local control (HR = 89; p = 0.006). Conclusions: GKSRS represents a feasible salvage option in patients with SCLC and brain metastases for whom previous WBI has failed. The status of patients' ECD is a dominant factor predictive of overall survival. Local control may be inferior to that seen with other cancer histological results, although the use of concurrent chemotherapy may help to improve this.

  18. HSPB1 Gene Polymorphisms Predict Risk of Mortality for US Patients After Radio(chemo)therapy for Non-Small Cell Lung Cancer

    SciTech Connect (OSTI)

    Xu Ting; Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas ; Wei Qingyi; Lopez Guerra, Jose Luis; Department of Radiation Oncology, Instituto Madrileno de Oncologia Wang Lie; Liu Zhensheng; Gomez, Daniel; O'Reilly, Michael; Lin, Steven Hsesheng; Zhuang Yan; Levy, Lawrence B.; Mohan, Radhe; Zhou Honghao; Liao Zhongxing

    2012-10-01

    Purpose: We investigated potential associations between single-nucleotide polymorphisms (SNPs) in the heat shock protein beta-1 (HSPB1) gene and overall survival in US patients with non-small cell lung cancer (NSCLC). Methods and Materials: Using available genomic DNA samples from 224 patients with NSCLC treated with definitive radio(chemo)therapy, we genotyped 2 SNPs of HSPB1 (NCBI SNP nos. rs2868370 and rs2868371). We used both Kaplan-Meier cumulative probability and Cox proportional hazards analyses to evaluate the effect of HSPB1 genotypes on survival. Results: Our cohort consisted of 117 men and 107 women, mostly white (79.5%), with a median age of 70 years. The median radiation dose was 66 Gy (range, 63-87.5 Gy), and 183 patients (82%) received concurrent platinum-based chemotherapy. The most common genotype of the rs2868371 SNP was CC (61%). Univariate and multivariate analyses showed that this genotype was associated with poorer survival than CG and GG genotypes (univariate hazard ratio [HR] = 1.39, 95% confidence interval [CI], 1.02-1.90; P=.037; multivariate HR = 1.39; 95% CI, 1.01-1.92; P=.045). Conclusions: Our results showed that the CC genotype of HSPB1 rs2868371 was associated with poorer overall survival in patients with NSCLC after radio(chemo)therapy, findings that contradict those of a previous study of Chinese patients. Validation of our findings with larger numbers of similar patients is needed, as are mechanical and clinical studies to determine the mechanism underlying these associations.

  19. Factors Affecting the Risk of Brain Metastasis in Small Cell Lung Cancer With Surgery: Is Prophylactic Cranial Irradiation Necessary for Stage I-III Disease?

    SciTech Connect (OSTI)

    Gong Linlin; Wang, Q.I.; Zhao Lujun; Yuan Zhiyong; Li Ruijian; Wang Ping

    2013-01-01

    Purpose: The use of prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC) with surgical resection has not been fully identified. This study undertook to assess the factors affecting the risk of brain metastases in patients with stage I-III SCLC after surgical resection. The implications of PCI treatment for these patients are discussed. Methods and Materials: One hundred twenty-six patients treated with surgical resection for stage I-III SCLC from January 1998-December 2009 were retrospectively analyzed to elucidate the risk factors of brain metastases. Log-rank test and Cox regression model were used to determine the risk factors of brain metastases. Results: The median survival time for this patient population was 34 months, and the 5-year overall survival rate was 34.9%. For the whole group, 23.0% (29/126) of the patients had evidence of metastases to brain. Pathologic stage not only correlated with overall survival but also significantly affected the risk of brain metastases. The 5-year survival rates for patients with pathologic stages I, II, and III were 54.8%, 35.6%, and 14.1%, respectively (P=.001). The frequency of brain metastases in patients with pathologic stages I, II, and III were 6.25% (2/32), 28.2% (11/39), and 29.1% (16/55) (P=.026), respectively. A significant difference in brain metastases between patients with complete resection and incomplete resection was also observed (20.5% vs 42.9%, P=.028). The frequency of brain metastases was not found to be correlated with age, sex, pathologic type, induction chemotherapy, adjuvant chemotherapy, or adjuvant radiation therapy. Conclusions: Stage I SCLC patients with complete resection had a low incidence of brain metastases and a favorable survival rate. Stage II-III disease had a higher incidence of brain metastases. Thus, PCI might have a role for stage II-III disease but not for stage I disease.

  20. Activation of protein kinase B (PKB/Akt) and risk of lung cancer among rural women in India who cook with biomass fuel

    SciTech Connect (OSTI)

    Roychoudhury, Sanghita; Mondal, Nandan Kumar; Mukherjee, Sayali; Dutta, Anindita; Siddique, Shabana; Ray, Manas Ranjan

    2012-02-15

    The impact of indoor air pollution (IAP) from biomass fuel burning on the risk of carcinogenesis in the airways has been investigated in 187 pre-menopausal women (median age 34 years) from eastern India who cooked exclusively with biomass and 155 age-matched control women from same locality who cooked with cleaner fuel liquefied petroleum gas. Compared with control, Papanicolau-stained sputum samples showed 3-times higher prevalence of metaplasia and 7-times higher prevalence of dysplasia in airway epithelial cell (AEC) of biomass users. Immunocytochemistry showed up-regulation of phosphorylated Akt (p-Akt{sup ser473} and p-Akt{sup thr308}) proteins in AEC of biomass users, especially in metaplastic and dysplastic cells. Compared with LPG users, biomass-using women showed marked rise in reactive oxygen species (ROS) generation and depletion of antioxidant enzyme, superoxide dismutase (SOD) indicating oxidative stress. There were 25 times more particulate pollutants (PM{sub 10} and PM{sub 2.5}), 72% more nitrogen dioxide and 4-times more particulate-laden benzo(a)pyrene, but no change in sulfur dioxide in indoor air of biomass-using households, and high performance liquid chromatography estimated 6-fold rise in the concentration of benzene metabolite trans,trans-muconic acid (t,t-MA) in urine of biomass users. Metaplasia and dysplasia, p-Akt expression and ROS generation were positively associated with PM and t,t-MA levels. It appears that cumulative exposure to biomass smoke increases the risk of lung carcinogenesis via oxidative stress-mediated activation of Akt signal transduction pathway. -- Highlights: ? Carcinogenesis in airway cells was examined in biomass and LPG using women. ? Metaplasia and dysplasia of epithelial cells were more prevalent in biomass users. ? Change in airway cytology was associated with oxidative stress and Akt activation. ? Biomass users had greater exposure to respirable PM, B(a)P and benzene. ? Cooking with biomass increases cancer risk in the airways via Akt activation.

  1. Does Response to Induction Chemotherapy Predict Survival for Locally Advanced Non-Small-Cell Lung Cancer? Secondary Analysis of RTOG 8804/8808

    SciTech Connect (OSTI)

    McAleer, Mary Frances; Moughan, Jennifer M.S.; Byhardt, Roger W.; Cox, James D.; Sause, William T.; Komaki, Ritsuko

    2010-03-01

    Purpose: Induction chemotherapy (ICT) improves survival compared with radiotherapy (RT) alone in locally advanced non-small-cell lung cancer (LANSCLC) patients with good prognostic factors. Concurrent chemoradiotherapy (CCRT) is superior to ICT followed by RT. The question arises whether ICT response predicts the outcome of patients subsequently treated with CCRT or RT. Methods and Materials: Between 1988 and 1992, 194 LANSCLC patients were treated prospectively with ICT (two cycles of vinblastine and cisplatin) and then CCRT (cisplatin plus 63 Gy for 7 weeks) in the Radiation Therapy Oncology Group 8804 trial (n = 30) or ICT and then RT (60 Gy/6 wk) on Radiation Therapy Oncology Group 8808 trial (n = 164). Of the 194 patients, 183 were evaluable and 141 had undergone a postinduction assessment. The overall survival (OS) of those with complete remission (CR) or partial remission (PR) was compared with that of patients with stable disease (SD) or progressive disease (PD) after ICT. Results: Of the 141 patients, 6, 30, 99, and 6 had CR, PR, SD, and PD, respectively. The log-rank test showed a significant difference (p <0.0001) in OS when the response groups were compared (CR/PR vs. SD/PD). On univariate and multivariate analyses, a trend was seen toward a response to ICT with OS (p = 0.097 and p = 0.06, respectively). A squamous histologic type was associated with worse OS on univariate and multivariate analyses (p = 0.031 and p = 0.018, respectively). SD/PD plus a squamous histologic type had a hazard ratio of 2.25 vs. CR/PR plus a nonsquamous histologic type (p = 0.007) on covariate analysis. Conclusion: The response to ICT was associated with a significant survival difference when the response groups were compared. A response to ICT showed a trend toward, but was not predictive of, improved OS in LANSCLC patients. Patients with SD/PD after ICT and a squamous histologic type had the poorest OS. These data suggest that patients with squamous LANSCLC might benefit from immediate RT or CCRT.

  2. The Impact of Extent and Location of Mediastinal Lymph Node Involvement on Survival in Stage III Non-Small Cell Lung Cancer Patients Treated With Definitive Radiotherapy

    SciTech Connect (OSTI)

    Fernandes, Annemarie T.; Mitra, Nandita; Xanthopoulos, Eric; Evans, Tracey; Stevenson, James; Langer, Corey; Kucharczuk, John C.; Lin, Lilie; Rengan, Ramesh

    2012-05-01

    Purpose: Several surgical series have identified subcarinal, contralateral, and multilevel nodal involvement as predictors of poor overall survival in patients with Stage III non-small-cell lung cancer (NSCLC) treated with definitive resection. This retrospective study evaluates the impact of extent and location of mediastinal lymph node (LN) involvement on survival in patients with Stage III NSCLC treated with definitive radiotherapy. Methods and Materials: We analyzed 106 consecutive patients with T1-4 N2-3 Stage III NSCLC treated with definitive radiotherapy at University of Pennsylvania between January 2003 and February 2009. For this analysis, mediastinal LN stations were divided into four mutually exclusive groups: supraclavicular, ipsilateral mediastinum, contralateral mediastinum, and subcarinal. Patients' conditions were then analyzed according to the extent of involvement and location of mediastinal LN stations. Results: The majority (88%) of patients received sequential or concurrent chemotherapy. The median follow-up time for survivors was 32.6 months. By multivariable Cox modeling, chemotherapy use (hazard ratio [HR]: 0.21 [95% confidence interval (CI): 0.07-0.63]) was associated with improved overall survival. Increasing primary tumor [18F]-fluoro-2-deoxy-glucose avidity (HR: 1.11 [CI: 1.06-1.19]), and subcarinal involvement (HR: 2.29 [CI: 1.11-4.73]) were significant negative predictors of overall survival. On univariate analysis, contralateral nodal involvement (HR: 0.70 [CI: 0.33-1.47]), supraclavicular nodal involvement (HR: 0.78 [CI: 0.38-1.67]), multilevel nodal involvement (HR: 0.97 [CI: 0.58-1.61]), and tumor size (HR: 1.04 [CI: 0.94-1.14]) did not predict for overall survival. Patients with subcarinal involvement also had lower rates of 2-year nodal control (51.2% vs. 74.9%, p = 0.047) and 2-year distant control (28.4% vs. 61.2%, p = 0.043). Conclusions: These data suggest that the factors that determine oncologic outcome in Stage III NSCLC patients treated with definitive radiotherapy are distinct from those observed in patients who undergo surgical resection. The ultimate efficacy of radiation in locally advanced NSCLC is dependent on the intrinsic biology of the tumor.

  3. Phase II Study of Accelerated High-Dose Radiotherapy With Concurrent Chemotherapy for Patients With Limited Small-Cell Lung Cancer: Radiation Therapy Oncology Group Protocol 0239

    SciTech Connect (OSTI)

    Komaki, Ritsuko; Paulus, Rebecca; Ettinger, David S.; Videtic, Gregory M.M.; Bradley, Jeffrey D.; Glisson, Bonnie S.; Sause, William T.; Curran, Walter J.; Choy, Hak

    2012-07-15

    Purpose: To investigate whether high-dose thoracic radiation given twice daily during cisplatin-etoposide chemotherapy for limited small-cell lung cancer (LSCLC) improves survival, acute esophagitis, and local control rates relative to findings from Intergroup trial 0096 (47%, 27%, and 64%). Patients and Methods: Patients were accrued over a 3-year period from 22 US and Canadian institutions. Patients with LSCLC and good performance status were given thoracic radiation to 61.2 Gy over 5 weeks (daily 1.8-Gy fractions on days 1-22, then twice-daily 1.8-Gy fractions on days 23-33). Cisplatin (60 mg/m{sup 2} IV) was given on day 1 and etoposide (120 mg/m{sup 2} IV) on days 1-3 and days 22-24, followed by 2 cycles of cisplatin plus etoposide alone. Patients who achieved complete response were offered prophylactic cranial irradiation. Endpoints included overall and progression-free survival; severe esophagitis (Common Toxicity Criteria v 2.0) and treatment-related fatalities; response (Response Evaluation Criteria in Solid Tumors); and local control. Results: Seventy-two patients were accrued from June 2003 through May 2006; 71 were evaluable (median age 63 years; 52% female; 58% Zubrod 0). Median survival time was 19 months; at 2 years, the overall survival rate was 36.6% (95% confidence interval [CI] 25.6%-47.7%), and progression-free survival 19.7% (95% CI 11.4%-29.6%). Thirteen patients (18%) experienced severe acute esophagitis, and 2 (3%) died of treatment-related causes; 41% achieved complete response, 39% partial response, 10% stable disease, and 6% progressive disease. The local control rate was 73%. Forty-three patients (61%) received prophylactic cranial irradiation. Conclusions: The overall survival rate did not reach the projected goal; however, rates of esophagitis were lower, and local control higher, than projected. This treatment strategy is now one of three arms of a prospective trial of chemoradiation for LSCLC (Radiation Therapy Oncology Group 0538/Cancer and Leukemia Group B 30610).

  4. Modeling the Risk of Radiation-Induced Acute Esophagitis for Combined Washington University and RTOG Trial 93-11 Lung Cancer Patients

    SciTech Connect (OSTI)

    Huang, Ellen X.; Bradley, Jeffrey D.; El Naqa, Issam [Department of Radiation Oncology, Washington University School of Medicine, St Louis, MO (United States); Hope, Andrew J.; Lindsay, Patricia E. [Princess Margaret Hospital, Toronto, ON (Canada); Bosch, Walter R.; Matthews, John W. [Department of Radiation Oncology, Washington University School of Medicine, St Louis, MO (United States); Sause, William T. [Department of Radiation Oncology, LDS Hospital, Salt Lake City, UT (United States); Graham, Mary V. [Department of Radiation Oncology, Phelps County Regional Hospital, Rolla, MO (United States); Deasy, Joseph O., E-mail: deasyj@mskcc.org [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

    2012-04-01

    Purpose: To construct a maximally predictive model of the risk of severe acute esophagitis (AE) for patients who receive definitive radiation therapy (RT) for non-small-cell lung cancer. Methods and Materials: The dataset includes Washington University and RTOG 93-11 clinical trial data (events/patients: 120/374, WUSTL = 101/237, RTOG9311 = 19/137). Statistical model building was performed based on dosimetric and clinical parameters (patient age, sex, weight loss, pretreatment chemotherapy, concurrent chemotherapy, fraction size). A wide range of dose-volume parameters were extracted from dearchived treatment plans, including Dx, Vx, MOHx (mean of hottest x% volume), MOCx (mean of coldest x% volume), and gEUD (generalized equivalent uniform dose) values. Results: The most significant single parameters for predicting acute esophagitis (RTOG Grade 2 or greater) were MOH85, mean esophagus dose (MED), and V30. A superior-inferior weighted dose-center position was derived but not found to be significant. Fraction size was found to be significant on univariate logistic analysis (Spearman R = 0.421, p < 0.00001) but not multivariate logistic modeling. Cross-validation model building was used to determine that an optimal model size needed only two parameters (MOH85 and concurrent chemotherapy, robustly selected on bootstrap model-rebuilding). Mean esophagus dose (MED) is preferred instead of MOH85, as it gives nearly the same statistical performance and is easier to compute. AE risk is given as a logistic function of (0.0688 Asterisk-Operator MED+1.50 Asterisk-Operator ConChemo-3.13), where MED is in Gy and ConChemo is either 1 (yes) if concurrent chemotherapy was given, or 0 (no). This model correlates to the observed risk of AE with a Spearman coefficient of 0.629 (p < 0.000001). Conclusions: Multivariate statistical model building with cross-validation suggests that a two-variable logistic model based on mean dose and the use of concurrent chemotherapy robustly predicts acute esophagitis risk in combined-data WUSTL and RTOG 93-11 trial datasets.

  5. Poster Thur Eve 10: Partial kV CBCT, complete kV CBCT and EPID in breast treatment: a dose comparison study for skin, breasts, heart and lungs

    SciTech Connect (OSTI)

    Roussin, E; Archambault, L K; Wierzbicki, W

    2014-08-15

    The advantages of kilovoltage cone beam CT (kV CBCT) imaging over electronic portal imaging device (EPID) such as accurate 3D anatomy, soft tissue visualization, fast rigid registration and enhanced precision on patient positioning has lead to its increasing use in clinics. The benefits of this imaging technique are at the cost of increasing the dose to healthy surrounding organs. Our center has moved toward the use of daily partial rotation kV CBCT to restrict the dose to healthy tissues. This study aims to better quantify radiation doses from different image-guidance techniques such as tangential EPID, complete and partial kV CBCT for breast treatments. Cross-calibrated ionization chambers and kV calibrated Gafchromic films were used to measure the dose to the heart, lungs, breasts and skin. It was found that performing partial kV CBCT decreases the heart dose by about 36%, the lungs dose by 31%, the contralateral breast dose by 41% and the ipsilateral breast dose by 43% when compared to a full rotation CBCT. The skin dose measured for a full rotation CBCT was about 0.8 cGy for the contralateral breast and about 0.3 cGy for the ipsilateral breast. The study is still ongoing and results on skin doses for partial rotation kV CBCT as well as for tangential EPID images are upcoming.

  6. Kids with disabilities inspire a musical instrument

    ScienceCinema (OSTI)

    Daily, Dan; Pfeifer, Kent

    2014-02-10

    The Midiwing is a musical instrument that unites music and computer technology for those who lack the experience, physical ability, or maturity to play music with traditional instruments. To create the instrument, Dan Daily, Director of Musicode Innovations, reworked and recoded Musical Instrument Digital Interface (MIDI) technology and introduced ergonomic design. He applied to the New Mexico Small Business Assistance (NMSBA) Program to receive help when he discovered the microcontroller he used was being phased out. Daily and Kent Pfeifer, an engineer at Sandia National Laboratories and musician himself, partnered to create a new state-of-the-art design.

  7. ANNUAL ACCOMPLISHMENT PLAN UPDATE FOR DISABLED VETERANS

    National Nuclear Security Administration (NNSA)

    ... The OLI established several new internal opportunities for employees, one of which is Fusion Forums in which employees at all levels of the organization are invited to an hour-long ...

  8. Semi Monthly Rates for Supplemental Disability

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    for your age and waiting period. 50 year old employee who is making 102,000 and is choosing a 30-day waiting period. Divide 102,000 by 12 to get 8,500 per month. 8,500 x...

  9. Kids with disabilities inspire a musical instrument

    SciTech Connect (OSTI)

    Daily, Dan; Pfeifer, Kent

    2013-11-21

    The Midiwing is a musical instrument that unites music and computer technology for those who lack the experience, physical ability, or maturity to play music with traditional instruments. To create the instrument, Dan Daily, Director of Musicode Innovations, reworked and recoded Musical Instrument Digital Interface (MIDI) technology and introduced ergonomic design. He applied to the New Mexico Small Business Assistance (NMSBA) Program to receive help when he discovered the microcontroller he used was being phased out. Daily and Kent Pfeifer, an engineer at Sandia National Laboratories and musician himself, partnered to create a new state-of-the-art design.

  10. ANNUAL ACCOMPLISHMENT PLAN UPDATE FOR DISABLED VETERANS

    National Nuclear Security Administration (NNSA)

    specific training and development needs. o Agency Oversight The NNSA Office of Human Capital Management developed new communication strategies for announcing Human Capital...

  11. Careers & the disABLED Career Expo

    Broader source: Energy.gov [DOE]

    Location: Ronald Reagan Bldg, Washington, DCAttendees:  Terri Sosa (Science)POC:  Donna FriendWebsite: http://bit.ly/1tlHhNr

  12. ANNUAL ACCOMPLISHMENT PLAN UPDATE FOR DISABLED VETERANS

    National Nuclear Security Administration (NNSA)

    3 Accomplishment Report Table of Contents October 2013 U.S. Department of Energy National Nuclear Security Administration FY 2013 NNSA DVAAP Report 1 Table of Contents * Plan Certification .........................................................................................Page 3 * Agency DVAAP Executive Summary................................................................. Page 4 * Organizational

  13. Rebate Program Serves Alaskans with Disabilities | Department...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    "So the idea was to come up with a program that worked and had minimal administrative costs, so most of the money would go to the rebates," said Cary Bolling, an Energy Specialist ...

  14. ANNUAL ACCOMPLISHMENT PLAN UPDATE FOR DISABLED VETERANS

    National Nuclear Security Administration (NNSA)

    throughout FY 2015. Efforts are also underway within NNSA to update and enhance marketing materials targeted towards the hiring of Veterans. o Promote and Develop One of the...

  15. Tumor Volume Combined With Number of Positive Lymph Node Stations Is a More Important Prognostic Factor Than TNM Stage for Survival of Non-Small-Cell Lung Cancer Patients Treated With (Chemo)radiotherapy

    SciTech Connect (OSTI)

    Dehing-Oberije, Cary [Department of Radiotherapy, University Hospital Maastricht, University Maastricht, MAASTRO Clinic, Research Institute Growth and Development (GROW), Maastricht (Netherlands)], E-mail: cary.dehing@maastro.nl; Ruysscher, Dirk de; Weide, Hiska van der [Department of Radiotherapy, University Hospital Maastricht, University Maastricht, MAASTRO Clinic, Research Institute Growth and Development (GROW), Maastricht (Netherlands); Hochstenbag, Monique [Department of Pulmonology, University Hospital Maastricht, Maastricht (Netherlands); Bootsma, Gerben [Department of Pulmonology, Atrium Medical Centre, Heerlen (Netherlands); Geraedts, Wiel [Department of Pulmonology, Maasland Hospital, Sittard (Netherlands); Pitz, Cordula [Department of Pulmonology, Laurentius Hospital, Roermond (Netherlands); Simons, Jean [Department of Pulmonology, Sint Jans Hospital, Weert (Netherlands); Teule, Jaap [Department of Nuclear Medicine, University Hospital Maastricht, Maastricht (Netherlands); Rahmy, Ali [Department of Nuclear Medicine, Atrium Medical Centre, Heerlen (Netherlands); Thimister, Paul [Department of Nuclear Medicine, Maasland Hospital, Sittard (Netherlands); Steck, Harald [Siemens Medical Solutions, Malvern, PA (United States); Lambin, Philippe [Department of Radiotherapy, University Hospital Maastricht, University Maastricht, MAASTRO Clinic, Research Institute Growth and Development (GROW), Maastricht (Netherlands)

    2008-03-15

    Purpose: The current tumor, node, metastasis system needs refinement to improve its ability to predict survival of patients with non-small-cell lung cancer (NSCLC) treated with (chemo)radiation. In this study, we investigated the prognostic value of tumor volume and N status, assessed by using fluorodeoxyglucose-positron emission tomography (PET). Patients and Methods: Clinical data from 270 consecutive patients with inoperable NSCLC Stages I-IIIB treated radically with (chemo)radiation were collected retrospectively. Diagnostic imaging was performed using either integrated PET-computed tomography or computed tomography and PET separately. The Kaplan-Meier method, as well as Cox regression, was used to analyze data. Results: Univariate survival analysis showed that number of positive lymph node stations (PLNSs), as well as N stage on PET, was associated significantly with survival. The final multivariate Cox model consisted of number of PLNSs, gross tumor volume (i.e., volume of the primary tumor plus lymph nodes), sex, World Health Organization performance status, and equivalent radiation dose corrected for time; N stage was no longer significant. Conclusions: Number of PLNSs, assessed by means of fluorodeoxyglucose-PET, was a significant factor for survival of patients with inoperable NSCLC treated with (chemo)radiation. Risk stratification for this group of patients should be based on gross tumor volume, number of PLNSs, sex, World Health Organization performance status, and equivalent radiation dose corrected for time.

  16. A Phase 3 Trial of Whole Brain Radiation Therapy and Stereotactic Radiosurgery Alone Versus WBRT and SRS With Temozolomide or Erlotinib for Non-Small Cell Lung Cancer and 1 to 3 Brain Metastases: Radiation Therapy Oncology Group 0320

    SciTech Connect (OSTI)

    Sperduto, Paul W.; Wang, Meihua; Robins, H. Ian; Schell, Michael C.; Werner-Wasik, Maria; Komaki, Ritsuko; Souhami, Luis; Buyyounouski, Mark K.; Khuntia, Deepak; Demas, William; Shah, Sunjay A.; Nedzi, Lucien A.; Perry, Gad; Suh, John H.; Mehta, Minesh P.

    2013-04-01

    Background: A phase 3 Radiation Therapy Oncology Group (RTOG) study subset analysis demonstrated improved overall survival (OS) with the addition of stereotactic radiosurgery (SRS) to whole brain radiation therapy (WBRT) in non-small cell lung cancer (NSCLC) patients with 1 to 3 brain metastases. Because temozolomide (TMZ) and erlotinib (ETN) cross the blood-brain barrier and have documented activity in NSCLC, a phase 3 study was designed to test whether these drugs would improve the OS associated with WBRT + SRS. Methods and Materials: NSCLC patients with 1 to 3 brain metastases were randomized to receive WBRT (2.5 Gy 15 to 37.5 Gy) and SRS alone, versus WBRT + SRS + TMZ (75 mg/m{sup 2}/day 21 days) or ETN (150 mg/day). ETN (150 mg/day) or TMZ (150-200 mg/m{sup 2}/day 5 days/month) could be continued for as long as 6 months after WBRT + SRS. The primary endpoint was OS. Results: After 126 patients were enrolled, the study closed because of accrual limitations. The median survival times (MST) for WBRT + SRS, WBRT + SRS + TMZ, and WBRT + SRS + ETN were qualitatively different (13.4, 6.3, and 6.1 months, respectively), although the differences were not statistically significant. Time to central nervous system progression and performance status at 6 months were better in the WBRT + SRS arm. Grade 3 to 5 toxicity was 11%, 41%, and 49% in arms 1, 2, and 3, respectively (P<.001). Conclusion: The addition of TMZ or ETN to WBRT + SRS in NSCLC patients with 1 to 3 brain metastases did not improve survival and possibly had a deleterious effect. Because the analysis is underpowered, these data suggest but do not prove that increased toxicity was the cause of inferior survival in the drug arms.

  17. Functional Polymorphisms of Base Excision Repair Genes XRCC1 and APEX1 Predict Risk of Radiation Pneumonitis in Patients With Non-Small Cell Lung Cancer Treated With Definitive Radiation Therapy

    SciTech Connect (OSTI)

    Yin Ming; Liao Zhongxing; Liu Zhensheng; Wang, Li-E; Gomez, Daniel; Komaki, Ritsuko; Wei Qingyi

    2011-11-01

    Purpose: To explore whether functional single nucleotide polymorphisms (SNPs) of base-excision repair genes are predictors of radiation treatment-related pneumonitis (RP), we investigated associations between functional SNPs of ADPRT, APEX1, and XRCC1 and RP development. Methods and Materials: We genotyped SNPs of ADPRT (rs1136410 [V762A]), XRCC1 (rs1799782 [R194W], rs25489 [R280H], and rs25487 [Q399R]), and APEX1 (rs1130409 [D148E]) in 165 patients with non-small cell lung cancer (NSCLC) who received definitive chemoradiation therapy. Results were assessed by both Logistic and Cox regression models for RP risk. Kaplan-Meier curves were generated for the cumulative RP probability by the genotypes. Results: We found that SNPs of XRCC1 Q399R and APEX1 D148E each had a significant effect on the development of Grade {>=}2 RP (XRCC1: AA vs. GG, adjusted hazard ratio [HR] = 0.48, 95% confidence interval [CI], 0.24-0.97; APEX1: GG vs. TT, adjusted HR = 3.61, 95% CI, 1.64-7.93) in an allele-dose response manner (Trend tests: p = 0.040 and 0.001, respectively). The number of the combined protective XRCC1 A and APEX1 T alleles (from 0 to 4) also showed a significant trend of predicting RP risk (p = 0.001). Conclusions: SNPs of the base-excision repair genes may be biomarkers for susceptibility to RP. Larger prospective studies are needed to validate our findings.

  18. Definitive Chemoradiation Therapy Following Surgical Resection or Radiosurgery Plus Whole-Brain Radiation Therapy in Non-Small Cell Lung Cancer Patients With Synchronous Solitary Brain Metastasis: A Curative Approach

    SciTech Connect (OSTI)

    Parlak, Cem; Mertsoylu, Hüseyin; Güler, Ozan Cem; Onal, Cem; Topkan, Erkan

    2014-03-15

    Purpose/Objectives: The aim of this study was to evaluate the impact of definitive thoracic chemoradiation therapy following surgery or stereotactic radiosurgery (SRS) and whole-brain radiation therapy (WBRT) on the outcomes of patients with non-small cell lung cancer (NSCLC) with synchronous solitary brain metastasis (SSBM). Methods and Materials: A total of 63 NSCLC patients with SSBM were retrospectively evaluated. Patients were staged using positron emission tomography-computed tomography in addition to conventional staging tools. Thoracic radiation therapy (TRT) with a total dose of 66 Gy in 2 Gy fractions was delivered along with 2 cycles of cisplatin-based chemotherapy following either surgery plus 30 Gy of WBRT (n=33) or SRS plus 30 Gy of WBRT (n=30) for BM. Results: Overall, the treatment was well tolerated. All patients received planned TRT, and 57 patients (90.5%) were also able to receive 2 cycles of chemotherapy. At a median follow-up of 25.3 months (7.1-52.1 months), the median months of overall, locoregional progression-free, neurological progression-free, and progression-free survival were 28.6, 17.7, 26.4, and 14.6, respectively. Both univariate and multivariate analyses revealed that patients with a T1-T2 thoracic disease burden (P=.001), a nodal stage of N0-N1 (P=.003), and no weight loss (P=.008) exhibited superior survival. Conclusions: In the present series, surgical and radiosurgical treatments directed toward SSBM in NSCLC patients were equally effective. The similarities between the present survival outcomes and those reported in other studies for locally advanced NSCLC patients indicate the potentially curative role of definitive chemoradiation therapy for highly selected patients with SSBM.

  19. Risk of Hippocampal Metastases in Small Cell Lung Cancer Patients at Presentation and After Cranial Irradiation: A Safety Profile Study for Hippocampal Sparing During Prophylactic or Therapeutic Cranial Irradiation

    SciTech Connect (OSTI)

    Kundapur, Vijayananda; Ellchuk, Tasha; Ahmed, Shahid; Gondi, Vinai

    2015-03-15

    Purpose: Neurocognitive impairment (NI) in patients with small cell lung cancer (SCLC) after whole brain radiation treatment (WBRT) is a significant cause of morbidity. Hippocampal avoidance (HA) during WBRT may mitigate or prevent NI in such patients. However, this has not been tested in SCLC patients. The estimated risk of metastases in the HA region (HM) in patients with SCLC at diagnosis or after WBRT is unknown. Our study aimed to determine the risk of HM in patients with SCLC and to assess correlated clinical factors. Methods and Materials: Patients with SCLC who experienced brain metastases (BM) at presentation (de novo) or after WBRT treated at the Saskatoon Cancer Centre between 2005 and 2012 were studied. Relevant neuroimaging was independently reviewed by a neuroradiologist. HM was defined as metastases within 5 mm of the hippocampus. Logistic regression analysis was performed to assess correlation between various clinical variables and HM. Results: Seventy eligible patients were identified. Of 59 patients presenting with de novo BM, 3 patients (5%, 95% confidence interval [CI]: 0%-10.7%) had HM. Collectively there were 359 (range, 1-33) de novo BM with 3 (0.8%, 95% CI: 0%-1.7%) HM deposits. Twenty patients experienced progression of metastatic disease in the brain after WBRT. Of the 20 patients, only 1 patient (5%, 95% CI: 0%-14.5%) experienced HM. On logistic regression, no factors significantly correlated with HM. Conclusion: The overall incidence of HM before or after WBRT in SCLC patients is low, providing preliminary support for the safety of HA during planned clinical trials of HA-WBRT for SCLC.

  20. Higher Biologically Effective Dose of Radiotherapy Is Associated With Improved Outcomes for Locally Advanced Non-Small Cell Lung Carcinoma Treated With Chemoradiation: An Analysis of the Radiation Therapy Oncology Group

    SciTech Connect (OSTI)

    Machtay, Mitchell; Movsas, Benjamin; Paulus, Rebecca; Gore, Elizabeth M.; Komaki, Ritsuko; Albain, Kathy; Sause, William T.; Curran, Walter J.

    2012-01-01

    Purpose: Patients treated with chemoradiotherapy for locally advanced non-small-cell lung carcinoma (LA-NSCLC) were analyzed for local-regional failure (LRF) and overall survival (OS) with respect to radiotherapy dose intensity. Methods and Materials: This study combined data from seven Radiation Therapy Oncology Group (RTOG) trials in which chemoradiotherapy was used for LA-NSCLC: RTOG 88-08 (chemoradiation arm only), 90-15, 91-06, 92-04, 93-09 (nonoperative arm only), 94-10, and 98-01. The radiotherapeutic biologically effective dose (BED) received by each individual patient was calculated, as was the overall treatment time-adjusted BED (tBED) using standard formulae. Heterogeneity testing was done with chi-squared statistics, and weighted pooled hazard ratio estimates were used. Cox and Fine and Gray's proportional hazard models were used for OS and LRF, respectively, to test the associations between BED and tBED adjusted for other covariates. Results: A total of 1,356 patients were analyzed for BED (1,348 for tBED). The 2-year and 5-year OS rates were 38% and 15%, respectively. The 2-year and 5-year LRF rates were 46% and 52%, respectively. The BED (and tBED) were highly significantly associated with both OS and LRF, with or without adjustment for other covariates on multivariate analysis (p < 0.0001). A 1-Gy BED increase in radiotherapy dose intensity was statistically significantly associated with approximately 4% relative improvement in survival; this is another way of expressing the finding that the pool-adjusted hazard ratio for survival as a function of BED was 0.96. Similarly, a 1-Gy tBED increase in radiotherapy dose intensity was statistically significantly associated with approximately 3% relative improvement in local-regional control; this is another way of expressing the finding that the pool-adjusted hazard ratio as a function of tBED was 0.97. Conclusions: Higher radiotherapy dose intensity is associated with improved local-regional control and survival in the setting of chemoradiotherapy.

  1. Workplace Charging Challenge Partner: American Lung Association...

    Office of Environmental Management (EM)

    The ALAC houses the Denver and Southern Colorado Clean Cities program, which focuses on the use of alternative fuels and petroleum reduction strategies, like plug-in electric ...

  2. Lung injury in dimethyl sulfate poisoning

    SciTech Connect (OSTI)

    Ip, M.; Wong, K.L.; Wong, K.F.; So, S.Y.

    1989-02-01

    Two manual laborers were exposed to dimethyl sulfate during work and sustained mucosal injury to the eyes and respiratory tract. In one of them, noncardiogenic pulmonary edema occurred and improved with high-dose methylprednisolone. On follow-up for 10 months, this patient developed persistent productive cough with no evidence of bronchiectasis or bronchial hyperreactivity.

  3. Utah R850-27 Geothermal Steam | Open Energy Information

    Open Energy Info (EERE)

    in Utah outlining the authority for the Utah School and Institutional Trust Lands Administration (UTLA) to administer trust land in the state, including the leasing of trust land...

  4. Operational Plan and Desktop Reference- Disability Employment Program

    Broader source: Energy.gov [DOE]

    DOE hiring increased during Recovery Act years and returned to normal rates during FY11 and FY12. This, combined with budgetary impacts resulted in a larger than normal reduction of total hires...

  5. SNL Phuysician's Certificate of Disability; SF 4560-G

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    work date has expired. Please note, while input from employee's personal health care provider is considered in making the determination on the return to work date, the...

  6. Sweet spot: Disabling antibiotic-resistant bacteria | Argonne...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Justin H.S. Breaux at (630) 252-5823 or media@anl.gov. Connect Find an Argonne expert by subject. Follow Argonne on Twitter, Facebook, Google+ and LinkedIn. For inquiries on...

  7. KPaul A Service Disabled Veteran-Owned Small Business

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    at other federal laboratories, Ann invited KPaul to attend Sandia's Economic Impact Summit in January 2011. The summit, which provided a forum to highlight the role...

  8. Application for Presidential Permit OE Docket No. PP-371 Northern Pass: Comments from The Weeks Lancaster Trust

    Broader source: Energy.gov [DOE]

    Application from Northern Pass to construct, operate and maintain electric transmission facilities at the U.S, - Canada Border.

  9. Pretreatment [{sup 18}F]-fluoro-2-deoxy-glucose Positron Emission Tomography Maximum Standardized Uptake Value as Predictor of Distant Metastasis in Early-Stage Non-Small Cell Lung Cancer Treated With Definitive Radiation Therapy: Rethinking the Role of Positron Emission Tomography in Personalizing Treatment Based on Risk Status

    SciTech Connect (OSTI)

    Nair, Vimoj J.; MacRae, Robert; Sirisegaram, Abby; Pantarotto, Jason R.

    2014-02-01

    Purpose: The aim of this study was to determine whether the preradiation maximum standardized uptake value (SUV{sub max}) of the primary tumor for [{sup 18}F]-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) has a prognostic significance in patients with Stage T1 or T2N0 non-small cell lung cancer (NSCLC) treated with curative radiation therapy, whether conventional or stereotactic body radiation therapy (SBRT). Methods and Materials: Between January 2007 and December 2011, a total of 163 patients (180 tumors) with medically inoperable histologically proven Stage T1 or T2N0 NSCLC and treated with radiation therapy (both conventional and SBRT) were entered in a research ethics board approved database. All patients received pretreatment FDG-PET / computed tomography (CT) at 1 institution with consistent acquisition technique. The medical records and radiologic images of these patients were analyzed. Results: The overall survival at 2 years and 3 years for the whole group was 76% and 67%, respectively. The mean and median SUV{sub max} were 8.1 and 7, respectively. Progression-free survival at 2 years with SUV{sub max} <7 was better than that of the patients with tumor SUV{sub max} ?7 (67% vs 51%; P=.0096). Tumors with SUV{sub max} ?7 were associated with a worse regional recurrence-free survival and distant metastasis-free survival. In the multivariate analysis, SUV{sub max} ?7 was an independent prognostic factor for distant metastasis-free survival. Conclusion: In early-stage NSCLC managed with radiation alone, patients with SUV{sub max} ?7 on FDG-PET / CT scan have poorer outcomes and high risk of progression, possibly because of aggressive biology. There is a potential role for adjuvant therapies for these high-risk patients with intent to improve outcomes.

  10. Ulcerative colitis and steroid-responsive, diffuse interstitial lung disease

    SciTech Connect (OSTI)

    Balestra, D.J.; Balestra, S.T.; Wasson, J.H.

    1988-07-01

    The authors describe a patient with ulcerative colitis and extracolonic manifestations in whom diffuse interstitial pulmonary disease developed that was responsive to glucocorticoid therapy one year after total proctocolectomy. The patient presented in December 1983 with a subacute course marked by cough and progressive exertional dyspnea, abnormal chest examination results, and a chest roentgenogram that revealed diffuse interstitital and alveolar infiltrates. A transbronchial biopsy specimen revealed a polymorphic interstitial infiltrate, mild interstitial fibrosis without apparent intraluminal fibrosis, and no vasculitis, granulomas, or significant eosinophilic infiltration. Within one week of the initiation of daily high-dose steroid therapy, the patient's symptoms dramatically improved; chest roentgenogram and forced vital capacity (60%) improved at a slower rate. All three measures deteriorated when alternate-day prednisone therapy was started but once again improved until the patient was totally asymptomatic, chest roentgenograms were normal, and forced vital capacity was 80% of the predicted value 2 1/2 years later.

  11. States Department of Energy's National Nuclear Security Administration...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Attack Trust Anchors as a Fail-Safe Example of trust anchor technology implemented on a COTS HMI and PLC to create a trusted ModBus communication Figure 2 For More Information:...

  12. Oregon Trust Agreement Planning Project : Potential Mitigations to the Impacts on Oregon Wildlife Resources Associated with Relevant Mainstem Columbia River and Willamette River Hydroelectric Projects.

    SciTech Connect (OSTI)

    United States. Bonneville Power Administration.

    1993-10-01

    A coalition of the Oregon wildlife agencies and tribes (the Oregon Wildlife Mitigation Coalition) have forged a cooperative effort to promote wildlife mitigation from losses to Oregon wildlife resources associated with the four mainstream Columbia River and the eight Willamette River Basin hydroelectric projects. This coalition formed a Joint Advisory Committee, made up of technical representatives from all of the tribes and agencies, to develop this report. The goal was to create a list of potential mitigation opportunities by priority, and to attempt to determine the costs of mitigating the wildlife losses. The information and analysis was completed for all projects in Oregon, but was gathered separately for the Lower Columbia and Willamette Basin projects. The coalition developed a procedure to gather information on potential mitigation projects and opportunities. All tribes, agencies and interested parties were contacted in an attempt to evaluate all proposed or potential mitigation. A database was developed and minimum criteria were established for opportunities to be considered. These criteria included the location of the mitigation site within a defined area, as well as other criteria established by the Northwest Power Planning Council. Costs were established for general habitats within the mitigation area, based on estimates from certified appraisers. An analysis of the cost effectiveness of various types of mitigation projects was completed. Estimates of operation and maintenance costs were also developed. The report outlines strategies for gathering mitigation potentials, evaluating them, determining their costs, and attempting to move towards their implementation.

  13. Santa Fe New Mexican: For cybersecurity, in quantum encryption...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    For cybersecurity, in quantum encryption we trust Santa Fe New Mexican: For cybersecurity, in quantum encryption we trust Los Alamos physicists developed a quantum random number...

  14. RAPID/Roadmap/3-UT-e | Open Energy Information

    Open Energy Info (EERE)

    Lease (Utah Trust Lands) (3-UT-e) The Utah School and Institutional Trust Lands Administration (UTLA) administers the sale, exchange, and lease of state school and institutional...

  15. Abandoned Uranium Mine Technical Services and Cleanup Industry...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Abandoned Uranium Mine Technical Services and Cleanup Industry Day In January 2015, the United States (U.S.) and the Anadarko Litigation Trust ("Litigation Trust") entered into a...

  16. ORSSAB Member Greg Paulus Served His Country, Helped People with Disabilities

    Broader source: Energy.gov [DOE]

    ORSSAB member Greg Paulus is a Top Gun. He earned that distinction flying F4 fighters for the Air Force.

  17. DIRECT COSTS OF DISABLING WORKPLACE INJURIES GROW 2.5 PERCENT

    Broader source: Energy.gov [DOE]

    April 7, 2003 Annual Liberty Mutual Workplace Safety Index Shows Direct Costs of the Three Leading Causes of Workplace Incidents Grew Significantly Faster...

  18. Voluntary Self-Identification of Disability Form CC-305 OMB Control...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    HIVAIDS * Multiple sclerosis (MS) * Impairments requiring the use of a wheelchair * Diabetes * Epilepsy * Schizophrenia * Muscular dystrophy * Missing limbs or partially missing...

  19. Careers and disAbled DC Career Expo | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    10:00AM to 3:00PM EST Ronald Reagan Building, 1300 Pennsylvania Ave., NW, Washington, DC 20004 POC: Donna Friend More Info Careers & Internships The White House USA.gov Energy.gov...

  20. POLICY GUIDANCE MEMORANDUM #32A Schedule A Appointments of Persons...

    Office of Environmental Management (EM)

    2A Schedule A Appointments of Persons with Disabilities and Appointments for Disabled Veterans POLICY GUIDANCE MEMORANDUM 32A Schedule A Appointments of Persons with Disabilities...

  1. SU-F-BRE-07: Experimental Validation of a Lung SBRT Technique...

    Office of Scientific and Technical Information (OSTI)

    an increasing number of clinics, including our center which recently treated its first patient. In order to validate this technique, the 3D dose distribution of the SBRT plan was...

  2. Lung Toxicity and Mutagenicity of Emissions From Heavy-Duty Compressed...

    Broader source: Energy.gov (indexed) [DOE]

    5 Diesel Engine Emissions Reduction (DEER) Conference Presentations and Posters PDF icon 2005deermauderly.pdf More Documents & Publications Relationship Between Composition and ...

  3. Comparison of direct exposure of human lung cells to modern engine...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Relationship Between Composition and Toxicity of Engine Emissions Comparative Toxicity of Combined Particle and Semi-Volatile Organic Fractioins of Gasoline and Diesel Emissions

  4. Tax Credits, Rebates & Savings | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Renewable Energy Trust Fund The renewable energy fund, known as the Massachusetts Renewable Energy Trust Fund, is supported by a non-bypassable surcharge of 0.0005 per...

  5. Tax Credits, Rebates & Savings | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Trust Fund The renewable energy fund, known as the Massachusetts Renewable Energy Trust Fund, is supported by a non-bypassable surcharge of 0.0005 per kilowatt-hour (0.5 mill...

  6. Tax Credits, Rebates & Savings | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Energy Trust Fund The renewable energy fund, known as the Massachusetts Renewable Energy Trust Fund, is supported by a non-bypassable surcharge of 0.0005 per kilowatt-hour (0.5...

  7. RAPID/Roadmap/3-OR-b | Open Energy Information

    Open Energy Info (EERE)

    Hydropower Solar Tools Contribute Contact Us Easements on Trust and Non-Trust Land (3-OR-b) An easement of this kind may be used for encroachments and transmission lines....

  8. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Hydroelectric (Small), Anaerobic Digestion, Fuel Cells using Renewable Fuels, Other Distributed Generation Technologies Efficiency Maine Trust- Energy Efficiency and...

  9. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Tribal Government, Agricultural, Low Income Residential Savings Category: Solar Photovoltaics, Wind (All), Wind (Small), Hydroelectric (Small) Efficiency Maine Trust In...

  10. Tax Credits, Rebates & Savings | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Tribal Government, Agricultural, Low Income Residential Savings Category: Solar Photovoltaics, Wind (All), Wind (Small), Hydroelectric (Small) Efficiency Maine Trust-...

  11. LED Lighting: Just the Facts, Please!

    Broader source: Energy.gov [DOE]

    Now there's another arsenal in the toolbox to help consumers find LED lights they can trust: the Lighting Facts™ label.

  12. Energizing Communities

    Broader source: Energy.gov [DOE]

    Presents Energize New York's tactics for building trust with community leaders and developing key relationships through social media platforms.

  13. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Equipment, Data Center Equipment, LED Lighting, Commercial Refrigeration Equipment Industrial and Agricultural Production Efficiency Program Energy Trust of Oregon offers...

  14. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Personal Computing Equipment, Reflective Roofs, Commercial Refrigeration Equipment Industrial and Agricultural Production Efficiency Program Energy Trust of Oregon offers...

  15. Tax Credits, Rebates & Savings | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Controls, Personal Computing Equipment, LED Lighting, Commercial Refrigeration Equipment Industrial and Agricultural Production Efficiency Program Energy Trust of Oregon offers...

  16. Tax Credits, Rebates & Savings | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Computing Equipment, Reflective Roofs, LED Lighting, Commercial Refrigeration Equipment Industrial and Agricultural Production Efficiency Program Energy Trust of Oregon offers...

  17. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Thermal Electric, Solar Photovoltaics, Wind (All), Biomass, Hydroelectric, Municipal Solid Waste, Tidal, Wave, Wind (Small), Hydroelectric (Small) Efficiency Maine Trust-...

  18. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    & Savings Tax Credits, Rebates & Savings Efficiency Maine Trust- Energy Efficiency and Renewable Resource Fund Funding Sources Eligibility: Commercial, Local Government,...

  19. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Other Distributed Generation Technologies Efficiency Maine Trust- Energy Efficiency and Renewable Resource Fund Funding Sources Eligibility: Commercial, Local Government,...

  20. T-706: Microsoft Fraudulent Digital Certificate Issued by DigiNotar

    Broader source: Energy.gov [DOE]

    Fraudulent Digital Certificate Issued by DigiNotar, a Certification Authority Present in the Trusted Root Certification Authorities

  1. Innovation Ecosystems Spur Rapid Growth for Startups, Entrepreneurs |

    Office of Environmental Management (EM)

    Department of Energy Innovation Ecosystems Spur Rapid Growth for Startups, Entrepreneurs Innovation Ecosystems Spur Rapid Growth for Startups, Entrepreneurs September 14, 2011 - 4:22pm Addthis Rich Earley, CEO of Clean Urban Energy presents at Clean Energy Trust's Clean Energy Challenge in March 2011 | Courtesy of Clean Energy Trust Rich Earley, CEO of Clean Urban Energy presents at Clean Energy Trust's Clean Energy Challenge in March 2011 | Courtesy of Clean Energy Trust Sarah Jane Maxted

  2. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Water Heater, Commercial Refrigeration Equipment Industrial and Agricultural Production Efficiency Program Energy Trust of Oregon offers the Industrial and Agricultural...

  3. POLICY GUIDANCE MEMORANDUM #32A Schedule A Appointments of Persons with

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Disabilities and Appointments for Disabled Veterans | Department of Energy 2A Schedule A Appointments of Persons with Disabilities and Appointments for Disabled Veterans POLICY GUIDANCE MEMORANDUM #32A Schedule A Appointments of Persons with Disabilities and Appointments for Disabled Veterans Establishes policy and procedures that ensure Schedule A appointments and appointments for disabled veterans are in support of mission accomplishments and are in accordance with merit system principles,

  4. Viscoelastic Model for Lung Parenchyma for Multi-Scale Modeling of Respiratory System, Phase II: Dodecahedral Micro-Model

    SciTech Connect (OSTI)

    Freed, Alan D.; Einstein, Daniel R.; Carson, James P.; Jacob, Rick E.

    2012-03-01

    In the first year of this contractual effort a hypo-elastic constitutive model was developed and shown to have great potential in modeling the elastic response of parenchyma. This model resides at the macroscopic level of the continuum. In this, the second year of our support, an isotropic dodecahedron is employed as an alveolar model. This is a microscopic model for parenchyma. A hopeful outcome is that the linkage between these two scales of modeling will be a source of insight and inspiration that will aid us in the final year's activity: creating a viscoelastic model for parenchyma.

  5. EV Community Readiness projects: American Lung Association of the Southwest (CO); Oregon Business Development Department (OR, WA)

    Broader source: Energy.gov [DOE]

    2013 DOE Hydrogen and Fuel Cells Program and Vehicle Technologies Program Annual Merit Review and Peer Evaluation Meeting

  6. DETERMINATION OF IN-VITRO LUNG SOLUBILITY AND INTAKE-TO-DOSE CONVERSION FACTOR FOR TRITIATED LANTHANUM NICKEL ALUMINUM ALLOY

    SciTech Connect (OSTI)

    Farfan, E.; Labone, T.; Staack, G.; Cheng, Y.; Zhou, Y.; Varallo, T.

    2011-11-11

    A sample of tritiated lanthanum nickel aluminum alloy (LaNi4.25Al0.75 or LANA.75) similar to that used at the Savannah River Site Tritium Facilities was analyzed to estimate the particle size distribution of this metal tritide powder and the rate, at which this material dissolves in the human respiratory tract after it is inhaled. This information is used to calculate the committed effective dose received by a worker after inhaling the material. These doses, which were calculated using the same methodology given in the DOE Tritium Handbook, are presented as inhalation intake-to-dose conversion factors (DCF). The DCF for this metal tritide is less than the DCF for tritiated water and radiation worker bioassay programs designed for tritiated water are adequate to monitor for intakes of this material.

  7. SU-E-J-79: Internal Tumor Volume Motion and Volume Size Assessment Using 4D CT Lung Data

    SciTech Connect (OSTI)

    Jurkovic, I; Stathakis, S; Li, Y; Patel, A; Vincent, J; Papanikolaou, N; Mavroidis, P

    2014-06-01

    Purpose: To assess internal tumor volume change through breathing cycle and associated tumor motion using the 4DCT data. Methods: Respiration induced volume change through breathing cycle and associated motion was analyzed for nine patients that were scanned during the different respiratory phases. The examined datasets were the maximum and average intensity projections (MIP and AIP) and the 10 phases of the respiratory cycle. The internal target volume (ITV) was delineated on each of the phases and the planning target volume (PTV) was then created by adding setup margins to the ITV. Tumor motion through the phases was assessed using the acquired 4DCT dataset, which was then used to determine if the margins used for the ITV creation successfully encompassed the tumor in three dimensions. Results: Results showed that GTV motion along the superior inferior axes was the largest in all the cases independent of the tumor location and/or size or the use of abdomen compression. The extent of the tumor motion was found to be connected with the size of the GTV. The smallest GTVs exhibited largest motion vector independent of the tumor location. The motion vector size varied through the phases depending on the tumor size and location and it was smallest for phases 20 and 30. The smaller the volume of the delineated GTV, the greater its volume difference through the different respiratory phases was. The average GTV volume change was largest for the phases 60 and 70. Conclusion: Even if GTV is delineated using both AIP and MIP datasets, its motion extent will exceed the used margins especially for the very small GTV volumes. When the GTV size is less than 10 cc it is recommended to use fusion of the GTVs through all the phases to create the planning ITV.

  8. POLICY GUIDANCE MEMORANDUM #33 - Requirements for DOE Delegated...

    Office of Environmental Management (EM)

    POLICY GUIDANCE MEMORANDUM 32A Schedule A Appointments of Persons with Disabilities and Appointments for Disabled Veterans POLICY GUIDANCE MEMORANDUM 31 - Procedures...

  9. WORKFORCE DIVERSITY TOWN HALL

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    ... and Executive Order 13078 of March 13, 1998 (Increasing Employment of Adults With Disabilities), sought to tap the skills of the millions of Americans living with disabilities. ...

  10. Secretary Jewell Announces Approval of Second Utility-Scale Solar Energy

    Energy Savers [EERE]

    Project on American Indian Trust Land | Department of Energy Secretary Jewell Announces Approval of Second Utility-Scale Solar Energy Project on American Indian Trust Land Secretary Jewell Announces Approval of Second Utility-Scale Solar Energy Project on American Indian Trust Land May 8, 2014 - 4:41pm Addthis As part of the Obama Administration's efforts to build strong and prosperous tribal communities and the Climate Action Plan to cut carbon pollution and create clean energy jobs,

  11. National Electricity Delivery Division

    Office of Environmental Management (EM)

    (DOE) Office of Electricity Delivery and Energy Reliability (OE) National Electricity Delivery Division Julie Ann Smith, PhD September 24, 2015 The Federal Indian Trust Responsibility is a legal obligation under which the United States has charged itself with moral obligations of the highest responsibility and trust toward American Indian tribes. (Seminole Nation v. United States, 1942; Cherokee Nation v. Georgia, 1831). "When the trust responsibility is acknowledged and upheld by the

  12. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Biomass Tax Credits, Rebates & Savings Tax Credits, Rebates & Savings Sustainable Energy Trust Fund The SETF is financed by a non-bypassable surcharge on the electric and...

  13. NW Natural (Gas)- Residential Energy Efficiency Rebate Program

    Broader source: Energy.gov [DOE]

    Energy Trust of Oregon administers energy efficiency rebate programs for both residential and commercial customers of NW Natural in Washington. Interested customers can see the program website...

  14. ORISE: Spokesperson Training

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    events. ORISE's spokesperson training covers: Trust and credibility Verbal and nonverbal communication Message development Working with the media News conference management...

  15. Tax Credits, Rebates & Savings | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Industrial and Agricultural Production Efficiency Program Energy Trust of Oregon offers the Industrial and Agricultural Production Efficiency Program to customers of Portland...

  16. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Tax Credits, Rebates & Savings Tax Credits, Rebates & Savings Industrial and Agricultural Production Efficiency Program Energy Trust of Oregon offers the Industrial and...

  17. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Tax Credits, Rebates & Savings Tax Credits, Rebates & Savings Sustainable Energy Trust Fund The SETF is financed by a non-bypassable surcharge on the electric and...

  18. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    State Government, Low Income Residential, Institutional Savings Category: Solar Photovoltaics Efficiency Maine Trust In 2009, the Act Regarding Maine's Energy Future...

  19. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Credits, Rebates & Savings Tax Credits, Rebates & Savings Efficiency Maine Trust- Energy Efficiency and Renewable Resource Fund Funding Sources Eligibility: Commercial, Local...

  20. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Utilities Savings Category: Geothermal Electric, Solar Thermal Electric, Solar Photovoltaics, Wind (All), Biomass, Wind (Small) Sustainable Energy Trust Fund The SETF is...

  1. Tax Credits, Rebates & Savings | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Trust Fund Renewable-energy projects eligible for RERTF support include wind energy, solar-thermal energy, photovoltaics, dedicated crops grown for energy production and...

  2. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Cooperative Utilities Savings Category: Geothermal Electric, Solar Thermal Electric, Solar Photovoltaics, Wind (All), Biomass, Wind (Small) Sustainable Energy Trust Fund The...

  3. Tax Credits, Rebates & Savings | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Trust Fund Renewable-energy projects eligible for RERTF support include wind energy, solar-thermal energy, photovoltaics, dedicated crops grown for energy production and organic...

  4. Colorado's 1st congressional district: Energy Resources | Open...

    Open Energy Info (EERE)

    LLC BrightPhase Energy C Lock Technology Clean Energy Innovation Center Colorado Governor s Energy Office Colorado State Bank and Trust Conergy, Inc. Continuum Partners Crimson...

  5. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Electric, Solar Photovoltaics, Wind (All), Biomass, Hydroelectric, Municipal Solid Waste, Tidal, Wave, Wind (Small), Hydroelectric (Small) Sustainable Energy Trust Fund The SETF is...

  6. Tax Credits, Rebates & Savings | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Electric, Solar Photovoltaics, Wind (All), Biomass, Hydroelectric, Municipal Solid Waste, Tidal, Wave, Wind (Small), Hydroelectric (Small) Energy Trust of Oregon Of the funds...

  7. Project Reports for Forest County Potawatomi Community- 2010 Project

    Broader source: Energy.gov [DOE]

    The Forest County Potawatomi Community (FCPC) will implement energy efficiency improvements in revitalizing its historic Milwaukee inner-city trust property.

  8. Montana - Instructions for Application for Utilities Across State...

    Open Energy Info (EERE)

    Lands Jump to: navigation, search OpenEI Reference LibraryAdd to library General: Montana - Instructions for Application for Utilities Across State Trust Lands Abstract This...

  9. 90-day Interim Report on Shale Gas Production - Secretary of...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    whether both current and future production can be done in an environmentally sound fashion that meets the needs of public trust. This 90-day report presents recommendations...

  10. Guidelines for Home Energy Professionals Project: Benefits for...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    instill industry value and trust. Travel across markets to find work and differentiate skills to gain a job with employers that value nationally recognized, transferrable Home...

  11. Tax Credits, Rebates & Savings | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Hydroelectric (Small), Anaerobic Digestion, Fuel Cells using Renewable Fuels Renewable Energy Trust Fund The renewable energy fund, known as the Massachusetts Renewable Energy...

  12. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Yes; specific technologies not identified Tax Credits, Rebates & Savings Tax Credits, Rebates & Savings Sustainable Energy Trust Fund The SETF is financed by a non-bypassable...

  13. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Yes; specific technologies not identified Tax Credits, Rebates & Savings Tax Credits, Rebates & Savings Efficiency Maine Trust- Energy Efficiency and Renewable Resource Fund...

  14. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Yes; specific technologies not identified Tax Credits, Rebates & Savings Tax Credits, Rebates & Savings Efficiency Maine Trust In 2009, the Act Regarding Maine's Energy Future...

  15. Technology Application R&D

    Broader source: Energy.gov [DOE]

    Technology application R&D projects monitor SSL technology advances and provide laboratory and field evaluations of emerging products. Impartial, trusted analysis from DOE identifies and...

  16. Biogas and Biomass to Energy Grant Program

    Broader source: Energy.gov [DOE]

    The Renewable Energy Resources Program (RERP) promotes the development of renewable energy in Illinois. This program is funded by the Renewable Energy Resources Trust Fund (RERTF)-- the state's...

  17. Tax Credits, Rebates & Savings | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Whole Building, CustomOthers pending approval, Other EE, Food Service Equipment, Data Center Equipment, Commercial Refrigeration Equipment Energy Trust of Oregon Of the...

  18. Tax Credits, Rebates & Savings | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    CustomOthers pending approval, Food Service Equipment, Commercial Cooking Equipment, Data Center Equipment, Commercial Refrigeration Equipment Energy Trust of Oregon Of the...

  19. Tax Credits, Rebates & Savings | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Energy Resources Trust Fund Renewable-energy projects eligible for RERTF support include wind energy, solar-thermal energy, photovoltaics, dedicated crops grown for energy...

  20. DOE Policy 141.1: Management of Cultural Resources (DOE, 2001...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    to raise the level of awareness and accountability among DOE contractors concerning the importance of the Department's cultural resource-related legal and trust responsibilities. ...

  1. Tax Credits, Rebates & Savings | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    NW Natural (Gas)- Business Energy Efficiency Rebate Program Energy Trust of Oregon administers energy efficiency rebate programs for both residential and commercial customers of NW...

  2. Tax Credits, Rebates & Savings | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    NW Natural (Gas)- Residential Energy Efficiency Rebate Program Energy Trust of Oregon administers energy efficiency rebate programs for both residential and commercial customers of...

  3. DOE Zero Energy Ready Home Second Production Builder Round Table

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    ... Branding and Messaging * Write a press release on the round table, listing attendees * ... that will be trusted more than builder marketing efforts DOE will continue leveraging a ...

  4. Tax Credits, Rebates & Savings | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Resources Trust Fund Renewable-energy projects eligible for RERTF support include wind energy, solar-thermal energy, photovoltaics, dedicated crops grown for energy production...

  5. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Clothes Washers Tax Credits, Rebates & Savings Tax Credits, Rebates & Savings Energy Trust of Oregon Of the funds collected by the electric utilities, 56.7% must be allocated...

  6. RCW 79.13 Land Leases | Open Energy Information

    Open Energy Info (EERE)

    RCW 79.13 Land LeasesLegal Abstract Washington statute governing the administration of land leases for state trust lands. Published NA Year Signed or Took Effect...

  7. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    ControlsSensors Tax Credits, Rebates & Savings Tax Credits, Rebates & Savings Energy Trust of Oregon Of the funds collected by the electric utilities, 56.7% must be...

  8. RAPID/Roadmap/3-NM-e | Open Energy Information

    Open Energy Info (EERE)

    Business Lease), developers pursuing geothermal projects on state trust lands where the temperature of the extractable resource is less than 250 degrees Fahrenheit may apply for...

  9. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Insulation, Windows, Roofs, CustomOthers pending approval, Other EE, Wind (Small), Personal Computing Equipment, Tankless Water Heater Energy Trust of Oregon Of the funds...

  10. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Solar Water Heat Tax Credits, Rebates & Savings Tax Credits, Rebates & Savings Sustainable Energy Trust Fund The SETF is financed by a non-bypassable surcharge on the electric...

  11. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Cooperative Utilities Tax Credits, Rebates & Savings Tax Credits, Rebates & Savings Energy Trust of Oregon Of the funds collected by the electric utilities, 56.7% must be...

  12. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Municipal Utilities Tax Credits, Rebates & Savings Tax Credits, Rebates & Savings Energy Trust of Oregon Of the funds collected by the electric utilities, 56.7% must be...

  13. Tax Credits, Rebates & Savings | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Hydroelectric (Small), Geothermal Direct-Use, Other Distributed Generation Technologies Industrial and Agricultural Production Efficiency Program Energy Trust of Oregon offers...

  14. Tax Credits, Rebates & Savings | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    DuctAir sealing, Motors, Motor VFDs, Agricultural Equipment, Food Service Equipment Industrial and Agricultural Production Efficiency Program Energy Trust of Oregon offers...

  15. Tax Credits, Rebates & Savings | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    approval, Other EE, Wind (Small), Personal Computing Equipment, Tankless Water Heater Industrial and Agricultural Production Efficiency Program Energy Trust of Oregon offers...

  16. Tax Credits, Rebates & Savings | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Equipment, CustomOthers pending approval, Other EE, Commercial Refrigeration Equipment Industrial and Agricultural Production Efficiency Program Energy Trust of Oregon offers...

  17. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    pending approval, Other EE, Fuel Cells using Renewable Fuels, Tankless Water Heater Industrial and Agricultural Production Efficiency Program Energy Trust of Oregon offers...

  18. Tax Credits, Rebates & Savings | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Reflective Roofs, LED Lighting, Tankless Water Heater, Commercial Refrigeration Equipment Industrial and Agricultural Production Efficiency Program Energy Trust of Oregon offers...

  19. Tax Credits, Rebates & Savings | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Doors, Siding, Roofs, Comprehensive MeasuresWhole Building, Other EE, Reflective Roofs Industrial and Agricultural Production Efficiency Program Energy Trust of Oregon offers...

  20. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    SystemsBuilding Controls, Motor VFDs, Agricultural Equipment, Other EE, LED Lighting Industrial and Agricultural Production Efficiency Program Energy Trust of Oregon offers...

  1. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    approval, Wind (Small), Geothermal Direct-Use, Other Distributed Generation Technologies Industrial and Agricultural Production Efficiency Program Energy Trust of Oregon offers...

  2. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Center Equipment, LED Lighting, Tankless Water Heater, Commercial Refrigeration Equipment Industrial and Agricultural Production Efficiency Program Energy Trust of Oregon offers...

  3. Tax Credits, Rebates & Savings | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Data Center Equipment, Reflective Roofs, LED Lighting, Commercial Refrigeration Equipment Industrial and Agricultural Production Efficiency Program Energy Trust of Oregon offers...

  4. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Pumps, CaulkingWeather-stripping, DuctAir sealing, Building Insulation, Windows, Doors Industrial and Agricultural Production Efficiency Program Energy Trust of Oregon offers...

  5. Tax Credits, Rebates & Savings | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Equipment, Comprehensive MeasuresWhole Building, Other EE, Reflective Roofs Industrial and Agricultural Production Efficiency Program Energy Trust of Oregon offers...

  6. Tax Credits, Rebates & Savings | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Siding, Roofs, Comprehensive MeasuresWhole Building, Other EE, Tankless Water Heater Industrial and Agricultural Production Efficiency Program Energy Trust of Oregon offers...

  7. Tax Credits, Rebates & Savings | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Agricultural Savings Category: Agricultural Equipment, CustomOthers pending approval Industrial and Agricultural Production Efficiency Program Energy Trust of Oregon offers...

  8. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Windows, Doors, Siding, Roofs, Comprehensive MeasuresWhole Building, Other EE Industrial and Agricultural Production Efficiency Program Energy Trust of Oregon offers...

  9. Tax Credits, Rebates & Savings | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Building Insulation, Windows, Siding, Roofs, Motors, CustomOthers pending approval Industrial and Agricultural Production Efficiency Program Energy Trust of Oregon offers...

  10. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Water Heaters, Heat Pumps, Energy Mgmt. SystemsBuilding Controls, Motors, Other EE Industrial and Agricultural Production Efficiency Program Energy Trust of Oregon offers...

  11. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Siding Tax Credits, Rebates & Savings Tax Credits, Rebates & Savings Industrial and Agricultural Production Efficiency Program Energy Trust of Oregon offers the Industrial and...

  12. Pueblo of Jemez- 2002 Project

    Broader source: Energy.gov [DOE]

    The Pueblo of Jemez is conducting a feasibility study to determine the potential for development of geothermal resources on Jemez Tribal Trust Lands.

  13. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Photovoltaics Tax Credits, Rebates & Savings Tax Credits, Rebates & Savings Sustainable Energy Trust Fund The SETF is financed by a non-bypassable surcharge on the electric and...

  14. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Electric, Solar Thermal Electric, Solar Photovoltaics, Wind (All), Biomass, Wind (Small) Sustainable Energy Trust Fund The SETF is financed by a non-bypassable surcharge on the...

  15. Project Reports for Pueblo of Jemez- 2002 Project

    Broader source: Energy.gov [DOE]

    The Pueblo of Jemez is conducting a feasibility study to determine the potential for development of geothermal resources on Jemez Tribal Trust Lands.

  16. Risk Identification and Assessment

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    can be easily and quickly corrected with little effect on people, mission, assets, finances, or stakeholder trust.|A benefit with little or no improvement of operations or...

  17. Streamflow

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Help BPA Home > Power > Modified Streamflows Rain drop OUR VISION "BPA is a trusted steward of the Columbia River Power System. We provide maximum power and environmental value...

  18. RAPID/Roadmap/12-WA-b | Open Energy Information

    Open Energy Info (EERE)

    Geothermal Hydropower Solar Tools Contribute Contact Us State Trust Lands Habitat Conservation Plan Compliance (12-WA-b) The State of Washington has a Habitat Conservation Plan...

  19. Newport Beach, California: Energy Resources | Open Energy Information

    Open Energy Info (EERE)

    LLC GCube Inland Energy Inc International Solar Consulting Nautilus Renewables Quercus Trust David Gelbaum Private investor References US Census Bureau Incorporated...

  20. Report: U.S. Military Accelerates Deployment of Clean Energy...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    is accelerating across military installations operated by the U.S. Department of Defense, according to a report released January 16 by The Pew Charitable Trusts. 'Power...

  1. Natural Gas Weekly Update, Printer-Friendly Version

    Annual Energy Outlook [U.S. Energy Information Administration (EIA)]

    oil and gas resources will be necessary even as efficiency improvements reduce demand and renewable sources become more available. In order to retain public trust environmentally...

  2. Tax Credits, Rebates & Savings | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    identified, Hydroelectric (Small), Anaerobic Digestion, Fuel Cells using Renewable Fuels Renewable Energy Trust Fund The renewable energy fund, known as the Massachusetts...

  3. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    (Small), Fuel Cells using Renewable Fuels Efficiency Maine Trust- Energy Efficiency and Renewable Resource Fund Funding Sources Eligibility: Commercial, Local Government,...

  4. Natural Gas Weekly Update

    Gasoline and Diesel Fuel Update (EIA)

    oil and gas resources will be necessary even as efficiency improvements reduce demand and renewable sources become more available. In order to retain public trust environmentally...

  5. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Digestion, Fuel Cells using Renewable Fuels Efficiency Maine Trust- Energy Efficiency and Renewable Resource Fund Funding Sources Eligibility: Commercial, Local Government,...

  6. Tax Credits, Rebates & Savings | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    technologies not identified, Wind (Small), Anaerobic Digestion, Fuel Cells using Renewable Fuels Energy Trust of Oregon Of the funds collected by the electric utilities, 56.7%...

  7. Tax Credits, Rebates & Savings | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    technologies not identified, Anaerobic Digestion, Fuel Cells using Renewable Fuels Renewable Energy Trust Fund The renewable energy fund, known as the Massachusetts Renewable...

  8. DOE Issues Agency Information Collection Extension for OE-417...

    Broader source: Energy.gov (indexed) [DOE]

    the U.S. Trust Territories) so that the Government may help prevent the physical or virtual disruption of the operation of any critical infrastructure. Comments regarding this...

  9. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Residential Tax Credits, Rebates & Savings Tax Credits, Rebates & Savings Energy Trust of Oregon Of the funds collected by the electric utilities, 56.7% must be allocated...

  10. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Tax Credits, Rebates & Savings Tax Credits, Rebates & Savings Sustainable Energy Trust Fund The SETF is financed by a non-bypassable surcharge on the electric and natural...

  11. UTU-086781 | Open Energy Information

    Open Energy Info (EERE)

    Field Office none provided Surface Manager BUREAU OF LAND MGMT Lessee 1 STANDARD STEAM TRUST LLC Lessee 2 none provided Effective Date 1312019 Expire Date Held By Production...

  12. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Water Heaters Tax Credits, Rebates & Savings Tax Credits, Rebates & Savings Energy Trust of Oregon Of the funds collected by the electric utilities, 56.7% must be allocated...

  13. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Utility Tax Credits, Rebates & Savings Tax Credits, Rebates & Savings Energy Trust of Oregon Of the funds collected by the electric utilities, 56.7% must be allocated...

  14. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Utilities Tax Credits, Rebates & Savings Tax Credits, Rebates & Savings Energy Trust of Oregon Of the funds collected by the electric utilities, 56.7% must be allocated...

  15. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Sensors Tax Credits, Rebates & Savings Tax Credits, Rebates & Savings Energy Trust of Oregon Of the funds collected by the electric utilities, 56.7% must be allocated...

  16. Tax Credits, Rebates & Savings | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    Efficiency Maine Trust- Renewable Resource Fund The PUC adopted rules requiring the state's utilities to offer customers the option of supporting the fund by checking off a...

  17. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Tax Credits, Rebates & Savings Tax Credits, Rebates & Savings Energy Efficiency Trust Fund Additional funds may be accumulated through non-compliance fees as part of the...

  18. Newdale Geothermal Project | Open Energy Information

    Open Energy Info (EERE)

    Geothermal Area Geothermal Region Geothermal Project Profile Developer Standard Steam Trust Project Type Hydrothermal GEA Development Phase Phase I - Resource Procurement and...

  19. Mary's River Geothermal Project | Open Energy Information

    Open Energy Info (EERE)

    Geothermal Area Geothermal Region Geothermal Project Profile Developer Standard Steam Trust Project Type Hydrothermal GEA Development Phase Phase I - Resource Procurement and...

  20. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Lighting Tax Credits, Rebates & Savings Tax Credits, Rebates & Savings Energy Trust of Oregon Of the funds collected by the electric utilities, 56.7% must be allocated towards...

  1. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Heat recovery Tax Credits, Rebates & Savings Tax Credits, Rebates & Savings Energy Trust of Oregon Of the funds collected by the electric utilities, 56.7% must be allocated...

  2. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Freezers Tax Credits, Rebates & Savings Tax Credits, Rebates & Savings Energy Trust of Oregon Of the funds collected by the electric utilities, 56.7% must be allocated...

  3. UTU-086778 | Open Energy Information

    Open Energy Info (EERE)

    Field Office none provided Surface Manager BUREAU OF LAND MGMT Lessee 1 STANDARD STEAM TRUST LLC Lessee 2 none provided Effective Date 1312019 Expire Date Held By Production...

  4. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Equipment Tax Credits, Rebates & Savings Tax Credits, Rebates & Savings Energy Trust of Oregon Of the funds collected by the electric utilities, 56.7% must be allocated...

  5. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Windows Tax Credits, Rebates & Savings Tax Credits, Rebates & Savings Energy Trust of Oregon Of the funds collected by the electric utilities, 56.7% must be allocated towards...

  6. Tirumala Tirupati Devasthanams TTD | Open Energy Information

    Open Energy Info (EERE)

    (TTD) Place: Andhra Pradesh, India Sector: Wind energy Product: This is an independant trust that manages the Tirumala Venkateswara Temple at Tirumala and owner of wind farm....

  7. NVN-077481 | Open Energy Information

    Open Energy Info (EERE)

    Field Office none provided Surface Manager BUREAU OF LAND MGMT Lessee 1 WILMINGTON TRUST CO TRUSTEE Lessee 2 none provided Effective Date 812005 Expire Date Held By...

  8. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Boilers Tax Credits, Rebates & Savings Tax Credits, Rebates & Savings Energy Trust of Oregon Of the funds collected by the electric utilities, 56.7% must be allocated towards...

  9. NVN-083967 | Open Energy Information

    Open Energy Info (EERE)

    Field Office none provided Surface Manager BUREAU OF LAND MGMT Lessee 1 WILMINGTON TRUST CO TRUSTEE Lessee 2 none provided Effective Date 8142007 Expire Date Held By...

  10. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Furnaces Tax Credits, Rebates & Savings Tax Credits, Rebates & Savings Energy Trust of Oregon Of the funds collected by the electric utilities, 56.7% must be allocated towards...

  11. UTU-086779 | Open Energy Information

    Open Energy Info (EERE)

    Field Office none provided Surface Manager BUREAU OF LAND MGMT Lessee 1 STANDARD STEAM TRUST LLC Lessee 2 none provided Effective Date 12192008 Expire Date Held By Production...

  12. UTU-086780 | Open Energy Information

    Open Energy Info (EERE)

    Field Office none provided Surface Manager BUREAU OF LAND MGMT Lessee 1 STANDARD STEAM TRUST LLC Lessee 2 none provided Effective Date 192009 Expire Date Held By Production...

  13. Mary's River SW Geothermal Project | Open Energy Information

    Open Energy Info (EERE)

    Geothermal Area Geothermal Region Geothermal Project Profile Developer Standard Steam Trust Project Type Hydrothermal GEA Development Phase Phase I - Resource Procurement and...

  14. Snake River Plain Geothermal Project | Open Energy Information

    Open Energy Info (EERE)

    Geothermal Area Geothermal Region Geothermal Project Profile Developer Standard Steam Trust Project Type Hydrothermal GEA Development Phase Phase I - Resource Procurement and...

  15. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    using Renewable Fuels Tax Credits, Rebates & Savings Tax Credits, Rebates & Savings Energy Trust of Oregon Of the funds collected by the electric utilities, 56.7% must be...

  16. Commercial Energy Efficiency Rebate for Existing Buildings

    Broader source: Energy.gov [DOE]

    Business customers retrofitting existing buildings through measures not covered under the standard incentive program can still receive financial assistance from Energy Trust through the custom...

  17. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Residential Tax Credits, Rebates & Savings Tax Credits, Rebates & Savings Sustainable Energy Trust Fund The SETF is financed by a non-bypassable surcharge on the electric and...

  18. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Cooperative Utilities Tax Credits, Rebates & Savings Tax Credits, Rebates & Savings Sustainable Energy Trust Fund The SETF is financed by a non-bypassable surcharge on the...

  19. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Institutional Tax Credits, Rebates & Savings Tax Credits, Rebates & Savings Sustainable Energy Trust Fund The SETF is financed by a non-bypassable surcharge on the electric and...

  20. Tax Credits, Rebates & Savings | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Cells using Non-Renewable Fuels, Landfill Gas, Heat recovery, Anaerobic Digestion, Fuel Cells using Renewable Fuels, Microturbines Energy Trust of Oregon Of the funds collected by...