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Title: Regional Lung Function Profiles of Stage I and III Lung Cancer Patients: An Evaluation for Functional Avoidance Radiation Therapy

Abstract

Purpose: The development of clinical trials is underway to use 4-dimensional computed tomography (4DCT) ventilation imaging to preferentially spare functional lung in patients undergoing radiation therapy. The purpose of this work was to generate data to aide with clinical trial design by retrospectively characterizing dosimetric and functional profiles for patients with different stages of lung cancer. Methods and Materials: A total of 118 lung cancer patients (36% stage I and 64% stage III) from 2 institutions were used for the study. A 4DCT-ventilation map was calculated using the patient's 4DCT imaging, deformable image registration, and a density-change–based algorithm. To assess each patient's spatial ventilation profile both quantitative and qualitative metrics were developed, including an observer-based defect observation and metrics based on the ventilation in each lung third. For each patient we used the clinical doses to calculate functionally weighted mean lung doses and metrics that assessed the interplay between the spatial location of the dose and high-functioning lung. Results: Both qualitative and quantitative metrics revealed a significant difference in functional profiles between the 2 stage groups (P<.01). We determined that 65% of stage III and 28% of stage I patients had ventilation defects. Average functionally weighted mean lung dose wasmore » 19.6 Gy and 5.4 Gy for stage III and I patients, respectively, with both groups containing patients with large spatial overlap between dose and high-function regions. Conclusion: Our 118-patient retrospective study found that 65% of stage III patients have regionally variant ventilation profiles that are suitable for functional avoidance. Our results suggest that regardless of disease stage, it is possible to have unique spatial interplay between dose and high-functional lung, highlighting the importance of evaluating the function of each patient and developing a personalized functional avoidance treatment approach.« less

Authors:
 [1]; ; ;  [1];  [2];  [3]; ;  [4]; ; ; ;  [1]
  1. Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado (United States)
  2. Department of Radiology, University of Colorado School of Medicine, Aurora, Colorado (United States)
  3. Department of Radiation Oncology, University of Texas Medical Branch, Galveston, Texas (United States)
  4. Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan (United States)
Publication Date:
OSTI Identifier:
22648746
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 95; Journal Issue: 4; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; AVOIDANCE; BIOMEDICAL RADIOGRAPHY; CLINICAL TRIALS; COMPUTERIZED TOMOGRAPHY; GY RANGE 01-10; GY RANGE 10-100; IMAGES; LUNGS; METRICS; NEOPLASMS; PATIENTS; RADIATION DOSES; RADIOTHERAPY

Citation Formats

Vinogradskiy, Yevgeniy, E-mail: yevgeniy.vinogradskiy@ucdenver.edu, Schubert, Leah, Diot, Quentin, Waxweiller, Timothy, Koo, Phillip, Castillo, Richard, Castillo, Edward, Guerrero, Thomas, Rusthoven, Chad, Gaspar, Laurie, Kavanagh, Brian, and Miften, Moyed. Regional Lung Function Profiles of Stage I and III Lung Cancer Patients: An Evaluation for Functional Avoidance Radiation Therapy. United States: N. p., 2016. Web. doi:10.1016/J.IJROBP.2016.02.058.
Vinogradskiy, Yevgeniy, E-mail: yevgeniy.vinogradskiy@ucdenver.edu, Schubert, Leah, Diot, Quentin, Waxweiller, Timothy, Koo, Phillip, Castillo, Richard, Castillo, Edward, Guerrero, Thomas, Rusthoven, Chad, Gaspar, Laurie, Kavanagh, Brian, & Miften, Moyed. Regional Lung Function Profiles of Stage I and III Lung Cancer Patients: An Evaluation for Functional Avoidance Radiation Therapy. United States. doi:10.1016/J.IJROBP.2016.02.058.
Vinogradskiy, Yevgeniy, E-mail: yevgeniy.vinogradskiy@ucdenver.edu, Schubert, Leah, Diot, Quentin, Waxweiller, Timothy, Koo, Phillip, Castillo, Richard, Castillo, Edward, Guerrero, Thomas, Rusthoven, Chad, Gaspar, Laurie, Kavanagh, Brian, and Miften, Moyed. 2016. "Regional Lung Function Profiles of Stage I and III Lung Cancer Patients: An Evaluation for Functional Avoidance Radiation Therapy". United States. doi:10.1016/J.IJROBP.2016.02.058.
@article{osti_22648746,
title = {Regional Lung Function Profiles of Stage I and III Lung Cancer Patients: An Evaluation for Functional Avoidance Radiation Therapy},
author = {Vinogradskiy, Yevgeniy, E-mail: yevgeniy.vinogradskiy@ucdenver.edu and Schubert, Leah and Diot, Quentin and Waxweiller, Timothy and Koo, Phillip and Castillo, Richard and Castillo, Edward and Guerrero, Thomas and Rusthoven, Chad and Gaspar, Laurie and Kavanagh, Brian and Miften, Moyed},
abstractNote = {Purpose: The development of clinical trials is underway to use 4-dimensional computed tomography (4DCT) ventilation imaging to preferentially spare functional lung in patients undergoing radiation therapy. The purpose of this work was to generate data to aide with clinical trial design by retrospectively characterizing dosimetric and functional profiles for patients with different stages of lung cancer. Methods and Materials: A total of 118 lung cancer patients (36% stage I and 64% stage III) from 2 institutions were used for the study. A 4DCT-ventilation map was calculated using the patient's 4DCT imaging, deformable image registration, and a density-change–based algorithm. To assess each patient's spatial ventilation profile both quantitative and qualitative metrics were developed, including an observer-based defect observation and metrics based on the ventilation in each lung third. For each patient we used the clinical doses to calculate functionally weighted mean lung doses and metrics that assessed the interplay between the spatial location of the dose and high-functioning lung. Results: Both qualitative and quantitative metrics revealed a significant difference in functional profiles between the 2 stage groups (P<.01). We determined that 65% of stage III and 28% of stage I patients had ventilation defects. Average functionally weighted mean lung dose was 19.6 Gy and 5.4 Gy for stage III and I patients, respectively, with both groups containing patients with large spatial overlap between dose and high-function regions. Conclusion: Our 118-patient retrospective study found that 65% of stage III patients have regionally variant ventilation profiles that are suitable for functional avoidance. Our results suggest that regardless of disease stage, it is possible to have unique spatial interplay between dose and high-functional lung, highlighting the importance of evaluating the function of each patient and developing a personalized functional avoidance treatment approach.},
doi = {10.1016/J.IJROBP.2016.02.058},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 4,
volume = 95,
place = {United States},
year = 2016,
month = 7
}
  • Purpose: To determine the comparative effectiveness of different stereotactic body radiation therapy (SBRT) dosing regimens for early-stage non–small-cell lung cancer, using a large national database, focusing on the relative impact of dose as a function of tumor stage. Methods and Materials: The study included patients in the National Cancer Database from 2003 to 2006 with T1-T2N0M0 inoperable lung cancer (n=498). The biologically effective dose (BED) was calculated according to the linear quadratic formula using an α/β ratio of 10. High versus lower-dose (HD vs LD) SBRT was defined as a calculated BED above or below 150 Gy. Overall survival was estimated using Kaplan-Meiermore » methods and Cox proportional hazard regression. Results: The 5 most common dose fractionation schemes (percentage of cohort) used were 20 Gy × 3 (34%), 12 Gy × 4 (16%), 18 Gy × 3 (10%), 15 Gy × 3 (10%), and 16 Gy × 3 (4%). The median calculated BED was 150 Gy (interquartile range 106-166 Gy). The 3-year overall survival (OS) for patients who received HD versus LD was 55% versus 46% (log–rank P=.03). On subset analysis of the T1 cohort there was no association between calculated BED and 3-year OS (61% vs 60% with HD vs LD, P=.9). Among the T2 cohort, patients receiving HD experienced superior 3-year OS (37% vs 24%, P=.01). On multivariable analysis, factors independently prognostic for mortality were female gender (hazard ratio [HR] 0.76, P=.01), T2 tumor (HR 1.99, P=.0001), and HD (HR 0.68, P=.001). Conclusions: This comparative effectiveness analysis of SBRT dose for patients with stage I non–small-cell lung cancer suggests that higher doses (>150 Gy BED) are associated with a significant survival benefit in patients with T2 tumors.« less
  • Purpose: To assess quantitatively the impact of incorporating functional lung imaging into intensity-modulated radiation therapy planning for locally advanced non-small cell lung cancer (NSCLC). Methods and Materials: Sixteen patients with advanced-stage NSCLC who underwent radiotherapy were included in this study. Before radiotherapy, each patient underwent lung perfusion imaging with single-photon-emission computed tomography and X-ray computed tomography (SPECT-CT). The SPECT-CT was registered with simulation CT and was used to segment the 50- and 90-percentile hyperperfusion lung (F50 lung and F90 lung). Two IMRT plans were designed and compared in each patient: an anatomic plan using simulation CT alone and a functionalmore » plan using SPECT-CT in addition to the simulation CT. Dosimetric parameters of the two types of plans were compared in terms of tumor coverage and avoidance of normal tissues. Results: In incorporating perfusion information in IMRT planning, the median reductions in the mean doses to the F50 and F90 lung in the functional plan were 2.2 and 4.2 Gy, respectively, compared with those in the anatomic plans. The median reductions in the percentage of volume irradiated with >5 Gy, >10 Gy, and >20 Gy in the functional plans were 7.1%, 6.0%, and 5.1%, respectively, for F50 lung, and 11.7%, 12.0%, and 6.8%, respectively, for F90 lung. A greater degree of sparing of the functional lung was achieved for patients with large perfusion defects compared with those with relatively uniform perfusion distribution. Conclusion: Function-guided IMRT planning appears to be effective in preserving functional lung in locally advanced-stage NSCLC patients.« less
  • Purpose: To compare, using the National Cancer Database, survival, pathologic, and surgical outcomes in patients with stage IIIA non-small cell lung cancer treated with differential doses of neoadjuvant chemoradiation therapy, with the aim to discern whether radiation dose escalation was associated with a comparative effectiveness benefit and/or toxicity risk. Methods and Materials: Patients in the National Cancer Database with stage IIIA non-small cell lung cancer treated with neoadjuvant chemoradiation therapy and surgery between 1998 and 2005 were analyzed. Dose strata were divided between 36 to 45 Gy (low-dose radiation therapy, LD-RT), 45 to 54 Gy (inclusive, standard-dose, SD-RT), and 54 to 74 Gymore » (high-dose, HD-RT). Outcomes included overall survival, residual nodal disease, positive surgical margin status, hospital length of stay, and adverse surgical outcomes (30-day mortality or readmission). Results: The cohort consisted of 1041 patients: 233 (22%) LD-RT, 584 (56%) SD-RT, and 230 (22%) HD-RT. The median, 3-year, and 5-year overall survival outcomes were 34.9 months, 48%, and 37%, respectively. On univariable analysis, patients treated with SD-RT experienced prolonged overall survival (median 38.3 vs 31.8 vs 29.0 months for SD-RT, LD-RT, and HD-RT, respectively, P=.0089), which was confirmed on multivariable analysis (hazard ratios 0.77 and 0.81 vs LD and HD, respectively). Residual nodal disease was seen less often after HD-RT (25.5% vs 31.8% and 37.5% for HD-RT, LD-RT, and SD-RT, respectively, P=.0038). Patients treated with SD-RT had fewer prolonged hospital stays. There were no differences in positive surgical margin status or adverse surgical outcomes between the cohorts. Conclusions: Neoadjuvant chemoradiation therapy between 45 and 54 Gy was associated with superior survival in comparison with doses above and below this threshold. Although this conclusion is limited by selection bias, clear candidates for trimodality therapy do not seem to achieve additional benefit with dose escalation.« less
  • Purpose: To investigate the ability of four-dimensional computed tomography (4D-CT)-derived ventilation images to identify regions of highly functional lung for avoidance in intensity-modulated radiotherapy (IMRT) planning in locally advanced non-small-cell lung cancer (NSCLC). Methods and Materials: The treatment-planning records from 21 patients with Stage III NSCLC were selected. Ventilation images were generated from the 4D-CT sets, and each was imported into the treatment-planning system. Ninetieth percentile functional volumes (PFV90), constituting the 10% of the lung volume where the highest ventilation occurs, were generated. Baseline IMRT plans were generated using the lung volume constraint on V20 (<35%), and two additional plansmore » were generated using constraints on the PFV90 without a volume constraint. Dose-volume and dose-function histograms (DVH, DFH) were generated and used to evaluate the planning target volume coverage, lung volume, and functional parameters for comparison of the plans. Results: The mean dose to the PFV90 was reduced by 2.9 Gy, and the DFH at 5 Gy (F5) was reduced by 9.6% (SE = 2.03%). The F5, F10, V5, and V10 were all significantly reduced from the baseline values. We identified a favorable subset of patients for whom there was a further significant improvement in the mean lung dose. Conclusions: Four-dimensional computed tomography-derived ventilation regions were successfully used as avoidance structures to reduce the DVH and DFH at 5 Gy in all cases. In a subset, there was also a reduction in the F10 and V10 without a change in the V20, suggesting that this technique could be safely used.« less
  • Purpose: To determine the effect of biologically effective dose (BED{sub 10}) and radiation treatment schedule on overall survival (OS) in patients with early-stage non-small cell lung cancer (NSCLC) undergoing stereotactic body radiation therapy (SBRT). Methods and Materials: Using data from 65 treatment centers in the United States, we retrospectively reviewed the records of T1-2 N0 NSCLC patients undergoing SBRT alone from 2006 to 2014. Biologically relevant covariates, including dose per fraction, number of fractions, and time between fractions, were used to quantify BED{sub 10} and radiation treatment schedule. The linear-quadratic equation was used to calculate BED{sub 10} and to generatemore » a dichotomous dose variable of <105 Gy versus ≥105 Gy BED{sub 10}. The primary outcome was OS. We used the Kaplan-Meier method, the log–rank test, and Cox proportional hazards regression with propensity score matching to determine whether prescription BED{sub 10} was associated with OS. Results: We identified 747 patients who met inclusion criteria. The median BED{sub 10} was 132 Gy, and 59 (7.7%) had consecutive-day fractions. Median follow-up was 41 months, and 452 patients (60.5%) had died by the conclusion of the study. The 581 patients receiving ≥105 Gy BED{sub 10} had a median survival of 28 months, whereas the 166 patients receiving <105 Gy BED{sub 10} had a median survival of 22 months (log–rank, P=.01). Radiation treatment schedule was not a significant predictor of OS on univariable analysis. After adjusting for T stage, sex, tumor histology, and Eastern Cooperative Oncology Group performance status, BED{sub 10} ≥105 Gy versus <105 Gy remained significantly associated with improved OS (hazard ratio 0.78, 95% confidence interval 0.62-0.98, P=.03). Propensity score matching on imbalanced variables within high- and low-dose cohorts confirmed a survival benefit with higher prescription dose. Conclusions: We found that dose escalation to 105 Gy BED{sub 10} and beyond may improve survival in NSCLC patients treated with SBRT.« less