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Title: A Population-Based Comparative Effectiveness Study of Radiation Therapy Techniques in Stage III Non-Small Cell Lung Cancer

Abstract

Purpose: Concerns have been raised about the potential for worse treatment outcomes because of dosimetric inaccuracies related to tumor motion and increased toxicity caused by the spread of low-dose radiation to normal tissues in patients with locally advanced non-small cell lung cancer (NSCLC) treated with intensity modulated radiation therapy (IMRT). We therefore performed a population-based comparative effectiveness analysis of IMRT, conventional 3-dimensional conformal radiation therapy (3D-CRT), and 2-dimensional radiation therapy (2D-RT) in stage III NSCLC. Methods and Materials: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify a cohort of patients diagnosed with stage III NSCLC from 2002 to 2009 treated with IMRT, 3D-CRT, or 2D-RT. Using Cox regression and propensity score matching, we compared survival and toxicities of these treatments. Results: The proportion of patients treated with IMRT increased from 2% in 2002 to 25% in 2009, and the use of 2D-RT decreased from 32% to 3%. In univariate analysis, IMRT was associated with improved overall survival (OS) (hazard ratio [HR] 0.90, P=.02) and cancer-specific survival (CSS) (HR 0.89, P=.02). After controlling for confounders, IMRT was associated with similar OS (HR 0.94, P=.23) and CSS (HR 0.94, P=.28) compared with 3D-CRT. Both techniques had superior OS compared withmore » 2D-RT. IMRT was associated with similar toxicity risks on multivariate analysis compared with 3D-CRT. Propensity score matched model results were similar to those from adjusted models. Conclusions: In this population-based analysis, IMRT for stage III NSCLC was associated with similar OS and CSS and maintained similar toxicity risks compared with 3D-CRT.« less

Authors:
 [1];  [2];  [1];  [3];  [1];  [3];  [1];  [3];  [1];  [3];  [3]
  1. Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States)
  2. Department of Radiation Medicine and Applied Science, University of California– San Diego, Moores Cancer Center, La Jolla, California (United States)
  3. (United States)
Publication Date:
OSTI Identifier:
22416497
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 88; Journal Issue: 4; Other Information: Copyright (c) 2014 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; COMPARATIVE EVALUATIONS; DIAGNOSIS; EPIDEMIOLOGY; HAZARDS; LUNGS; MEDICAL SURVEILLANCE; MULTIVARIATE ANALYSIS; NEOPLASMS; PATIENTS; RADIATION DOSES; RADIOTHERAPY; TOXICITY

Citation Formats

Harris, Jeremy P., Murphy, James D., Hanlon, Alexandra L., University of Pennsylvania School of Nursing, Philadelphia, Pennsylvania, Le, Quynh-Thu, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California, Loo, Billy W., E-mail: BWLoo@Stanford.edu, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California, Diehn, Maximilian, E-mail: diehn@Stanford.edu, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California, and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California. A Population-Based Comparative Effectiveness Study of Radiation Therapy Techniques in Stage III Non-Small Cell Lung Cancer. United States: N. p., 2014. Web. doi:10.1016/J.IJROBP.2013.12.010.
Harris, Jeremy P., Murphy, James D., Hanlon, Alexandra L., University of Pennsylvania School of Nursing, Philadelphia, Pennsylvania, Le, Quynh-Thu, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California, Loo, Billy W., E-mail: BWLoo@Stanford.edu, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California, Diehn, Maximilian, E-mail: diehn@Stanford.edu, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California, & Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California. A Population-Based Comparative Effectiveness Study of Radiation Therapy Techniques in Stage III Non-Small Cell Lung Cancer. United States. doi:10.1016/J.IJROBP.2013.12.010.
Harris, Jeremy P., Murphy, James D., Hanlon, Alexandra L., University of Pennsylvania School of Nursing, Philadelphia, Pennsylvania, Le, Quynh-Thu, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California, Loo, Billy W., E-mail: BWLoo@Stanford.edu, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California, Diehn, Maximilian, E-mail: diehn@Stanford.edu, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California, and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California. Sat . "A Population-Based Comparative Effectiveness Study of Radiation Therapy Techniques in Stage III Non-Small Cell Lung Cancer". United States. doi:10.1016/J.IJROBP.2013.12.010.
@article{osti_22416497,
title = {A Population-Based Comparative Effectiveness Study of Radiation Therapy Techniques in Stage III Non-Small Cell Lung Cancer},
author = {Harris, Jeremy P. and Murphy, James D. and Hanlon, Alexandra L. and University of Pennsylvania School of Nursing, Philadelphia, Pennsylvania and Le, Quynh-Thu and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California and Loo, Billy W., E-mail: BWLoo@Stanford.edu and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California and Diehn, Maximilian, E-mail: diehn@Stanford.edu and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California},
abstractNote = {Purpose: Concerns have been raised about the potential for worse treatment outcomes because of dosimetric inaccuracies related to tumor motion and increased toxicity caused by the spread of low-dose radiation to normal tissues in patients with locally advanced non-small cell lung cancer (NSCLC) treated with intensity modulated radiation therapy (IMRT). We therefore performed a population-based comparative effectiveness analysis of IMRT, conventional 3-dimensional conformal radiation therapy (3D-CRT), and 2-dimensional radiation therapy (2D-RT) in stage III NSCLC. Methods and Materials: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify a cohort of patients diagnosed with stage III NSCLC from 2002 to 2009 treated with IMRT, 3D-CRT, or 2D-RT. Using Cox regression and propensity score matching, we compared survival and toxicities of these treatments. Results: The proportion of patients treated with IMRT increased from 2% in 2002 to 25% in 2009, and the use of 2D-RT decreased from 32% to 3%. In univariate analysis, IMRT was associated with improved overall survival (OS) (hazard ratio [HR] 0.90, P=.02) and cancer-specific survival (CSS) (HR 0.89, P=.02). After controlling for confounders, IMRT was associated with similar OS (HR 0.94, P=.23) and CSS (HR 0.94, P=.28) compared with 3D-CRT. Both techniques had superior OS compared with 2D-RT. IMRT was associated with similar toxicity risks on multivariate analysis compared with 3D-CRT. Propensity score matched model results were similar to those from adjusted models. Conclusions: In this population-based analysis, IMRT for stage III NSCLC was associated with similar OS and CSS and maintained similar toxicity risks compared with 3D-CRT.},
doi = {10.1016/J.IJROBP.2013.12.010},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 4,
volume = 88,
place = {United States},
year = {Sat Mar 15 00:00:00 EDT 2014},
month = {Sat Mar 15 00:00:00 EDT 2014}
}
  • 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 performed a systematic review and pooled analysis to compare clinical outcomes of stereotactic body radiation therapy (SBRT) and radiofrequency ablation (RFA) for the treatment of medically inoperable stage I non-small cell lung cancer. Methods and Materials: A comprehensive literature search for published trials from 2001 to 2012 was undertaken. Pooled analyses were performed to obtain overall survival (OS) and local tumor control rates (LCRs) and adverse events. Regression analysis was conducted considering each study's proportions of stage IA and age. Results: Thirty-one studies on SBRT (2767 patients) and 13 studies on RFA (328 patients) were eligible. The LCR (95%more » confidence interval) at 1, 2, 3, and 5 years for RFA was 77% (70%-85%), 48% (37%-58%), 55% (47%-62%), and 42% (30%-54%) respectively, which was significantly lower than that for SBRT: 97% (96%-98%), 92% (91%-94%), 88% (86%-90%), and 86% (85%-88%) (P<.001). These differences remained significant after correcting for stage IA and age (P<.001 at 1 year, 2 years, and 3 years; P=.04 at 5 years). The effect of RFA was not different from that of SBRT on OS (P>.05). The most frequent complication of RFA was pneumothorax, occurring in 31% of patients, whereas that for SBRT (grade ≥3) was radiation pneumonitis, occurring in 2% of patients. Conclusions: Compared with RFA, SBRT seems to have a higher LCR but similar OS. More studies with larger sample sizes are warranted to validate such findings.« less
  • Purpose: To compare dose-volume histograms (DVH) in patients with non-small-cell lung cancer (NSCLC) treated by photon or proton radiotherapy. Methods and Materials: Dose-volume histograms were compared between photon, including three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), and proton plans at doses of 66 Gy, 87.5 Gy in Stage I (n = 10) and 60-63 Gy, and 74 Gy in Stage III (n 15). Results: For Stage I, the mean total lung V5, V10, and V20 were 31.8%, 24.6%, and 15.8%, respectively, for photon 3D-CRT with 66 Gy, whereas they were 13.4%, 12.3%, and 10.9%, respectively, with proton withmore » dose escalation to 87.5 cobalt Gray equivalents (CGE) (p = 0.002). For Stage III, the mean total lung V5, V10, and V20 were 54.1%, 46.9%, and 34.8%, respectively, for photon 3D-CRT with 63 Gy, whereas they were 39.7%, 36.6%, and 31.6%, respectively, for proton with dose escalation to 74 CGE (p = 0.002). In all cases, the doses to lung, spinal cord, heart, esophagus, and integral dose were lower with proton therapy even compared with IMRT. Conclusions: Proton treatment appears to reduce dose to normal tissues significantly, even with dose escalation, compared with standard-dose photon therapy, either 3D-CRT or IMRT.« less
  • Purpose: To compare dose volume histograms of intensity-modulated proton therapy (IMPT) with those of intensity-modulated radiation therapy (IMRT) and passive scattering proton therapy (PSPT) for the treatment of stage IIIB non-small-cell lung cancer (NSCLC) and to explore the possibility of individualized radical radiotherapy. Methods and Materials: Dose volume histograms designed to deliver IMRT at 60 to 63 Gy, PSPT at 74 Gy, and IMPT at the same doses were compared and the use of individualized radical radiotherapy was assessed in patients with extensive stage IIIB NSCLC (n = 10 patients for each approach). These patients were selected based on theirmore » extensive disease and were considered to have no or borderline tolerance to IMRT at 60 to 63 Gy, based on the dose to normal tissue volume constraints (lung volume receiving 20 Gy [V20] of <35%, total mean lung dose <20 Gy; spinal cord dose, <45 Gy). The possibility of increasing the total tumor dose with IMPT for each patient without exceeding the dose volume constraints (maximum tolerated dose [MTD]) was also investigated. Results: Compared with IMRT, IMPT spared more lung, heart, spinal cord, and esophagus, even with dose escalation from 63 Gy to 83.5 Gy, with a mean MTD of 74 Gy. Compared with PSPT, IMPT allowed further dose escalation from 74 Gy to a mean MTD of 84.4 Gy (range, 79.4-88.4 Gy) while all parameters of normal tissue sparing were kept at lower or similar levels. In addition, IMPT prevented lower-dose target coverage in patients with complicated tumor anatomies. Conclusions: IMPT reduces the dose to normal tissue and allows individualized radical radiotherapy for extensive stage IIIB NSCLC.« less
  • Purpose: To determine the accuracy of four-dimensional computed tomography (4D-CT) scanning techniques in institutions participating in a Phase III trial of surgery vs. stereotactic radiotherapy (SBRT) for lung cancer. Methods and Materials: All 9 centers performed a 4D-CT scan of a motion phantom (Quasar, Modus Medical Devices) in accordance with their in-house imaging protocol for SBRT. A cylindrical cedar wood insert with plastic spheres of 15 mm (o15) and 30 mm (o30) diameter was moved in a cosine-based pattern, with an extended period in the exhale position to mimic the actual breathing motion. A range of motion of R =more » 15 and R = 25 mm and breathing period of T = 3 and T = 6 s were used. Positional and volumetric imaging accuracy was analyzed using Pinnacle version 8.1x at various breathing phases, including the mid-ventilation phase and maximal intensity projections of the spheres. Results: Imaging using eight CT scanners (Philips, Siemens, GE) and one positron emission tomography-CT scanner (Institution 3, Siemens) was investigated. The imaging protocols varied widely among the institutions. No strong correlation was found between the specific scan protocol parameters and the observed results. Deviations in the maximal intensity projection volumes averaged 1.9% (starting phase of the breathing cycle [o]15, R = 15), 12.3% (o15, R = 25), and -0.9% (o30, R = 15). The end-expiration volume deviations (13.4%, o15 and 2.5%, o30), were, on average, smaller than the end-inspiration deviations (20.7%, o15 and 4.5%, o30), which, in turn, were smaller than the mid-ventilation deviations (32.6%, o15 and 8.0%, o30). A slightly larger variation in the mid-ventilation origin position was observed (mean, -0.2 mm; range, -3.6-4.2) than in the maximal intensity projection origin position (mean, -0.1 mm; range, -2.5-2.5). The range of motion was generally underestimated (mean, -1.5 mm; range, -5.5-1). Conclusions: Notable differences were seen in the 4D-CT imaging protocols for SBRT among centers. However, the observed deviations in target volumes were generally small. They were slightly larger for the mid-ventilation phases and smallest for the end-expiration phases. Steps to optimize and standardize the 4D-CT scanning protocols for SBRT are desirable.« less