skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: MO-FG-CAMPUS-TeP3-01: A Model of Baseline Shift to Improve Robustness of Proton Therapy Treatments of Moving Tumors

Abstract

Purpose: The shift in mean position of a moving tumor also known as “baseline shift”, has been modeled, in order to automatically generate uncertainty scenarios for the assessment and robust optimization of proton therapy treatments in lung cancer. Methods: An average CT scan and a Mid-Position CT scan (MidPCT) of the patient at the planning time are first generated from a 4D-CT data. The mean position of the tumor along the breathing cycle is represented by the GTV contour in the MidPCT. Several studies reported both systematic and random variations of the mean tumor position from fraction to fraction. Our model can simulate this baseline shift by generating a local deformation field that moves the tumor on all phases of the 4D-CT, without creating any non-physical artifact. The deformation field is comprised of normal and tangential components with respect to the lung wall in order to allow the tumor to slip within the lung instead of deforming the lung surface. The deformation field is eventually smoothed in order to enforce its continuity. Two 4D-CT series acquired at 1 week of interval were used to validate the model. Results: Based on the first 4D-CT set, the model was able to generatemore » a third 4D-CT that reproduced the 5.8 mm baseline-shift measured in the second 4D-CT. Water equivalent thickness (WET) of the voxels have been computed for the 3 average CTs. The root mean square deviation of the WET in the GTV is 0.34 mm between week 1 and week 2, and 0.08 mm between the simulated data and week 2. Conclusion: Our model can be used to automatically generate uncertainty scenarios for robustness analysis of a proton therapy plan. The generated scenarios can also feed a TPS equipped with a robust optimizer. Kevin Souris, Ana Barragan, and Dario Di Perri are financially supported by Televie Grants from F.R.S.-FNRS.« less

Authors:
; ; ; ;  [1];  [1];  [2]
  1. Universite catholique de Louvain, Brussels (Belgium)
  2. (Belgium)
Publication Date:
OSTI Identifier:
22653918
Resource Type:
Journal Article
Resource Relation:
Journal Name: Medical Physics; Journal Volume: 43; Journal Issue: 6; Other Information: (c) 2016 American Association of Physicists in Medicine; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 61 RADIATION PROTECTION AND DOSIMETRY; COMPUTERIZED TOMOGRAPHY; DEFORMATION; GENES; IMAGE PROCESSING; LUNGS; NEOPLASMS; PROTON BEAMS; RADIOTHERAPY; SIMULATION

Citation Formats

Souris, K, Barragan Montero, A, Di Perri, D, Geets, X, Lee, J, Sterpin, E, and KU Leuven, Leuven. MO-FG-CAMPUS-TeP3-01: A Model of Baseline Shift to Improve Robustness of Proton Therapy Treatments of Moving Tumors. United States: N. p., 2016. Web. doi:10.1118/1.4957381.
Souris, K, Barragan Montero, A, Di Perri, D, Geets, X, Lee, J, Sterpin, E, & KU Leuven, Leuven. MO-FG-CAMPUS-TeP3-01: A Model of Baseline Shift to Improve Robustness of Proton Therapy Treatments of Moving Tumors. United States. doi:10.1118/1.4957381.
Souris, K, Barragan Montero, A, Di Perri, D, Geets, X, Lee, J, Sterpin, E, and KU Leuven, Leuven. 2016. "MO-FG-CAMPUS-TeP3-01: A Model of Baseline Shift to Improve Robustness of Proton Therapy Treatments of Moving Tumors". United States. doi:10.1118/1.4957381.
@article{osti_22653918,
title = {MO-FG-CAMPUS-TeP3-01: A Model of Baseline Shift to Improve Robustness of Proton Therapy Treatments of Moving Tumors},
author = {Souris, K and Barragan Montero, A and Di Perri, D and Geets, X and Lee, J and Sterpin, E and KU Leuven, Leuven},
abstractNote = {Purpose: The shift in mean position of a moving tumor also known as “baseline shift”, has been modeled, in order to automatically generate uncertainty scenarios for the assessment and robust optimization of proton therapy treatments in lung cancer. Methods: An average CT scan and a Mid-Position CT scan (MidPCT) of the patient at the planning time are first generated from a 4D-CT data. The mean position of the tumor along the breathing cycle is represented by the GTV contour in the MidPCT. Several studies reported both systematic and random variations of the mean tumor position from fraction to fraction. Our model can simulate this baseline shift by generating a local deformation field that moves the tumor on all phases of the 4D-CT, without creating any non-physical artifact. The deformation field is comprised of normal and tangential components with respect to the lung wall in order to allow the tumor to slip within the lung instead of deforming the lung surface. The deformation field is eventually smoothed in order to enforce its continuity. Two 4D-CT series acquired at 1 week of interval were used to validate the model. Results: Based on the first 4D-CT set, the model was able to generate a third 4D-CT that reproduced the 5.8 mm baseline-shift measured in the second 4D-CT. Water equivalent thickness (WET) of the voxels have been computed for the 3 average CTs. The root mean square deviation of the WET in the GTV is 0.34 mm between week 1 and week 2, and 0.08 mm between the simulated data and week 2. Conclusion: Our model can be used to automatically generate uncertainty scenarios for robustness analysis of a proton therapy plan. The generated scenarios can also feed a TPS equipped with a robust optimizer. Kevin Souris, Ana Barragan, and Dario Di Perri are financially supported by Televie Grants from F.R.S.-FNRS.},
doi = {10.1118/1.4957381},
journal = {Medical Physics},
number = 6,
volume = 43,
place = {United States},
year = 2016,
month = 6
}
  • Purpose: Dose-weighted linear energy transfer (dLET) has been shown to be useful for the analysis of late effects in proton therapy. This study presents the results of the testing of the dLET concept for intensity modulated proton therapy (IMPT) with a discrete spot scanning beam system without use of an aperture or compensator (AC). Methods: IMPT (no AC) and broad beams (BB) with (AC) were simulated in the TOPAS and FLUKA code systems. Information from the independently tested Monte Carlo Damage Simulation (MCDS) was integrated into the FLUKA code systems to account for spatial variations in the RBE for protonsmore » and other light ions using an endpoint of DNA double strand break (DSB) induction. Results: The proton spectra for IMPT beams at the depths beyond the distal edge contain a tail of high energy protons up to 100 MeV. The integral from the tail is compatible with the number of 5–8 MeV protons at the tip of the Bragg peak (BP). The dose averaged energy (dEav) decreases to 7 MeV at the tip of (BP) and then increases to about 15 MeV beyond the distal edge. Neutrons produced in the nozzle are two orders of magnitude higher for BB with AC than for IMPT in low energy part of the spectra. The dLET values beyond of the distal edge of the BP are 5 times larger for the IMPT than for BB with the AC. Contrarily, negligible differences are seen in the RBE estimates for IMPT and BB with AC beyond the distal edge of the BP. Conclusion: The analysis of late effects in IMPT with a spot scanning and double scattering or scanning techniques with AC may requires both dLET and RBE as quantitative parameters to characterize effects beyond the distal edge of the BP.« less
  • Purpose: Validate implementation of a published RBE model for DSB induction (RBEDSB) in several general purpose Monte Carlo (MC) code systems and the RayStation™ treatment planning system (TPS). For protons and other light ions, DSB induction is a critical initiating molecular event that correlates well with the RBE for cell survival. Methods: An efficient algorithm to incorporate information on proton and light ion RBEDSB from the independently tested Monte Carlo Damage Simulation (MCDS) has now been integrated into MCNP (Stewart et al. PMB 60, 8249–8274, 2015), FLUKA, TOPAS and a research build of the RayStation™ TPS. To cross-validate the RBEDSBmore » model implementation LET distributions, depth-dose and lateral (dose and RBEDSB) profiles for monodirectional monoenergetic (100 to 200 MeV) protons incident on a water phantom are compared. The effects of recoil and secondary ion production ({sub 2}H{sub +}, {sub 3}H{sub +}, {sub 3}He{sub 2+}, {sub 4}He{sub 2+}), spot size (3 and 10 mm), and transport physics on beam profiles and RBEDSB are examined. Results: Depth-dose and RBEDSB profiles among all of the MC models are in excellent agreement using a 1 mm distance criterion (width of a voxel). For a 100 MeV proton beam (10 mm spot), RBEDSB = 1.2 ± 0.03 (− 2–3%) at the tip of the Bragg peak and increases to 1.59 ± 0.3 two mm distal to the Bragg peak. RBEDSB tends to decrease as the kinetic energy of the incident proton increases. Conclusion: The model for proton RBEDSB has been accurately implemented into FLUKA, MCNP, TOPAS and the RayStation™TPS. The transport of secondary light ions (Z > 1) has a significant impact on RBEDSB, especially distal to the Bragg peak, although light ions have a small effect on (dosexRBEDSB) profiles. The ability to incorporate spatial variations in proton RBE within a TPS creates new opportunities to individualize treatment plans and increase the therapeutic ratio. Dr. Erik Traneus is employed full-time as a Research Scientist at RaySearch Laboratories. The research build of the RayStation used in the study was made available to the University of Washington free of charge. RaySearch Laboratories did not provide any monetary support for the reported studies.« less
  • Purpose: Introducing Monte Carlo based dose calculation algorithms into proton therapy planning systems (TPS) leads to improved accuracy. However accurate modelling of the proton pencil beam impinging the patient is necessary. Current approaches rely on measurement-driven reconstruction of phase-space and spectrum properties, typically constrained to analytical model functions. In this study a detailed Monte Carlo model of the complete cyclotron-based delivery system was created with the aim of providing more representative beam properties at treatment position. Methods: A model of the Varian Probeam proton system from the cyclotron exit to isocenter was constructed in the TOPAS Monte Carlo framework. Themore » beam evolution through apertures and magnetic elements was validated using Transport/Turtle calculations and additionally against measurements from the Probeam™ system at Scripps Proton Therapy Center (SPTC) in San Diego, CA. A voxelized water phantom at isocenter allowed for comparison of the dose-depth curve from the Probeam model with that of a corresponding Gaussian beam over the entire energy range (70–240 MeV). Measurements of relative beam fluence cross-profiles and depth-dose curves at and around isocenter were also compared to the MC results. Results: The simulated TOPAS beam envelope was found to agree with both the Transport/Turtle and measurements to within 5% for most of the beamline. The MC predicted energy spectrum at isocenter was found to deviate increasingly from Gaussian at energies below 160 MeV. The corresponding effects on the depth dose curve agreed well with measurements. Conclusion: Given the flexibility of TOPAS and available details of the delivery system, an accurate characterization of a proton pencil beam at isocenter is possible. Incorporation of the MC derived properties of the proton pencil beam can eliminate analytical approximations and ultimately increase treatment plan accuracy and quality. Both authors are employees of Varian Medical Systems.« less
  • Purpose: To measure the increase in in vitro radiosensitivity for A549 lung carcinoma cells due to gold nanoparticle (GNP) radiation dose enhancement in both traditional monolayer and three dimensional (3D) cell culture models. Methods: A γH2AX immunofluorescence assay is performed on monolayer A549 cell culture and quantitatively analyzed to measure the increase in double strand breaks (DSBs) resulting from GNP dose enhancement. A clonogenic survival assay (CSA) is then performed on monolayer A549 cell culture to assess true viability after treatment. And lastly, another γH2AX assay is performed on 3D A549 multicellular nodules overlaid on a bed of growth factormore » reduced matrigel to measure dose response in a model that better recapitulates treatment response to actual tumors in vivo. Results: The first γH2AX assay performed on the monolayer cell culture shows a significant increase in DSBs due to GNP dose enhancement. The maximum average observed increase in normalized fluorescent intensity for monolayer cell culture is 171% for the 6Gy-treatment groups incubated in 0.556 mg Au/ml solution. The CSA performed on monolayer cell culture also shows considerable GNP dose enhancement. The maximum decrease in the normalized surviving fraction is 12% for the 4Gy-treatment group incubated in 0.556 mg Au/ml. And lastly, the GNP dose enhancement is confirmed to be mitigated in three dimensional cell culture models as compared to the traditional monolayer model. The maximum average observed dose enhancement for 3D cell culture is 19% for the 6Gy-treatment groups and incubated in 0.556 mg Au/ml. Conclusion: A marked increase in radiosensitivity is observed for A549 lung carcinoma cells when treated with GNPs plus radiation as opposed to radiation alone. Traditional monolayer cell culture also shows a much more pronounced radiation dose enhancement than 3D cell culture.« less
  • Purpose: Recent studies have shown that the presence of Gold Nanoparticles (GNPs) in tumor tissue can lead to significant dose enhancement (DE) during External Beam Radiation Therapy (EBRT). In this in-silico study we investigate EBRT with in-situ dose painting using GNPs released from cylindrically shaped GNP-loaded fiducials. Methods: Reported Biologically Target/Tumor Volumes (BTVs) for 12 prostate carcinoma patients were employed in this study. Distribution of the GNPs after burst release from the fiducial (1.5mm diameter and 5mm length) located in the center of the spherically assumed BTV were modeled by isotropic and free diffusion without boundary condition and under themore » assumption of superposition. An experimentally determined diffusion coefficient for 10nm nanoparticles was adapted for investigating other GNP sizes (2, 5, 15, and 20nm) using the Stokes-Einstein equation. The maximum size of GNPs to achieve a minimal DE Factor (DEF) of 1.1 for 6MV EBRT using a fiducial-load of 30mg/g was calculated for typical periods of 14 and 21 days after implantation. Further, the minimal fiducial-load needed to achieve a clinically significant DEF of 1.2 was computed for 2nm GNPs. Results: Results showed that a minimal DEF of 1.1 could be reached for the smallest patient BTV using a maximal GNP size of 10nm and 20nm after 14 and 21 days, respectively. With increasing BTV smaller GNPs are required to ensure the same DEF. In particular, the largest BTV requires 2nm GNPs for periods of 14 and 21 days. Meanwhile, the required fiducial-load to reach a minimal DEF of 1.2 after 14 days was found in the range of 17mg/g and 59mg/g for all reported BTVs. Conclusion: This preliminary study indicates a strong dependence on GNP size and fiducial-load to realize a significant DE. The findings avail further research towards development of GNP-loaded fiducials for significantly enhancing radiotherapy for cancer patients.« less