Long-term prospective outcomes of intensity modulated radiotherapy for locally advanced lung cancer a secondary analysis of a randomized clinical trial Journal Article


Authors: Chun, S. G.; Hu, C.; Komaki, R. U.; Timmerman, R. D.; Schild, S. E.; Bogart, J. A.; Dobelbower, M. C.; Bosch, W.; Kavadi, V. S.; Narayan, S.; Iyengar, P.; Robinson, C.; Rothman, J.; Raben, A.; Augspurger, M. E.; MacRae, R. M.; Paulus, R.; Bradley, J. D.
Article Title: Long-term prospective outcomes of intensity modulated radiotherapy for locally advanced lung cancer a secondary analysis of a randomized clinical trial
Abstract: IMPORTANCE The optimal radiotherapy technique for unresectable locally advanced non-small cell lung cancer (NSCLC) is controversial, so evaluating long-term prospective outcomes of intensity-modulated radiotherapy (IMRT) is important. OBJECTIVE To compare long-term prospective outcomes of patients receiving IMRT and 3-dimensional conformal radiotherapy (3D-CRT) with concurrent carboplatin/paclitaxel for locally advanced NSCLC. DESIGN, SETTING, AND PARTICIPANTS A secondary analysis of a prospective phase 3 randomized clinical trial NRG Oncology-RTOG 0617 assessed 483 patients receiving chemoradiotherapy (3D-CRT vs IMRT) for locally advanced NSCLC based on stratification. MAIN OUTCOMES AND MEASURES Long-term outcomeswere analyzed, including overall survival (OS), progression-free survival (PFS), time to local failure, development of second cancers, and severe grade 3 or higher adverse events (AEs) per Common Terminology Criteria for Adverse Events, version 3. The percentage of an organ volume (V) receiving a specified amount of radiation in units of Gy is reported as V(radiation dose). RESULTS Of 483 patients (median [IQR] age, 64 [57-70] years; 194 [40.2%] female), 228 (47.2%) received IMRT, and 255 (52.8%) received 3D-CRT (median [IQR] follow-up, 5.2 [4.8-6.0] years). IMRT was associated with a 2-fold reduction in grade 3 or higher pneumonitis AEs compared with 3D-CRT (8 [3.5%] vs 21 [8.2%]; P = .03). On univariate analysis, heart V20, V40, and V60 were associated with worse OS (hazard ratios, 1.06 [95% CI, 1.04-1.09]; 1.09 [95%CI, 1.05-1.13]; 1.16 [95%CI, 1.09-1.24], respectively; all P < .001). IMRT significantly reduced heart V40 compared to 3D-CRT (16.5%vs 20.5%; P < .001). Heart V40 (<20%) had better OS than V40 (≥20%) (median [IQR], 2.5 [2.1-3.1] years vs 1.7 [1.5-2.0] years; P < .001). On multivariable analysis, heart V40 (≥20%), was associated with worse OS (hazard ratio, 1.34 [95%CI, 1.06-1.70]; P = .01), whereas lung V5 and age had no association with OS. Patients receiving IMRT and 3D-CRT had similar rates of developing secondary cancers (15 [6.6%] vs 14 [5.5%]) with long-term follow-up. CONCLUSIONS AND RELEVANCE These findings support the standard use of IMRT for locally advanced NSCLC. IMRT should aim to minimize lung V20 and heart V20 to V60, rather than constraining low-dose radiation bath. Lung V5 and age were not associated with survival and should not be considered a contraindication for chemoradiotherapy. © 2024 American Medical Association. All rights reserved.
Keywords: adult; controlled study; treatment outcome; aged; middle aged; major clinical study; overall survival; clinical trial; intensity modulated radiation therapy; paclitaxel; cancer radiotherapy; follow up; antineoplastic agent; prospective study; prospective studies; carboplatin; progression free survival; randomized controlled trial; antineoplastic combined chemotherapy protocols; carcinoma, non-small-cell lung; lung neoplasms; radiotherapy; lung cancer; pathology; cetuximab; pneumonia; lung tumor; radiotherapy, intensity-modulated; phase 3 clinical trial; radiotherapy, conformal; chemoradiotherapy; non small cell lung cancer; secondary analysis; progression-free survival; conformal radiotherapy; adverse event; procedures; propensity score; distant metastasis free survival; humans; human; male; female; article
Journal Title: JAMA Oncology
Volume: 10
Issue: 8
ISSN: 2374-2437
Publisher: American Medical Association  
Date Published: 2024-08-01
Start Page: 1111
End Page: 1115
Language: English
DOI: 10.1001/jamaoncol.2024.1841
PUBMED: 38935373
PROVIDER: scopus
PMCID: PMC11211986
DOI/URL:
Notes: Article -- Source: Scopus
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  1. Puneeth Iyengar
    50 Iyengar