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. 2024 Jun 27:e241841.
doi: 10.1001/jamaoncol.2024.1841. Online ahead of print.

Long-Term Prospective Outcomes of Intensity Modulated Radiotherapy for Locally Advanced Lung Cancer: A Secondary Analysis of a Randomized Clinical Trial

Stephen G Chun  1 , Chen Hu  2   3 , Ritsuko U Komaki  4 , Robert D Timmerman  5 , Steven E Schild  6 , Jeffrey A Bogart  7 , Michael C Dobelbower  8 , Walter Bosch  9 , Vivek S Kavadi  10 , Samir Narayan  11 , Puneeth Iyengar  12 , Clifford Robinson  9 , Jan Rothman  13 , Adam Raben  14 , Mark E Augspurger  15 , Robert M MacRae  16 , Rebecca Paulus  2   3 , Jeffrey D Bradley  17
Affiliations

Long-Term Prospective Outcomes of Intensity Modulated Radiotherapy for Locally Advanced Lung Cancer: A Secondary Analysis of a Randomized Clinical Trial

Stephen G Chun et al. JAMA Oncol. .

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 outcomes were 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.

Trial registration: ClinicalTrials.gov Identifier: NCT00533949.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Chun reported grants from the National Cancer Institute (NCI) and Eli Lily during the conduct of the study; personal fees from AstraZeneca, ViewRay, Henry Ford Health Systems, Japanese Society for Radiation Oncology, Binaytara Foundation, Elsevier, American Society for Radiation Oncology, and grants from Nektar Therapeutics outside the submitted work. Dr Hu reported grants from NCI during the conduct of the study; grants from RTOG and personal fees from Johnson & Johnson Enterprise Innovation Inc outside the submitted work. Dr Dobelbower reported personal fees from RTOG during the conduct of the study; and grants from Varian Medical Systems outside the submitted work. Dr Bosch reported grants from NCI CA18647 and U24CA189893 during the conduct of the study. Dr Iyengar reported being on the advisory board for AstraZeneca and Novocure and grants from Incyte outside the submitted work. Dr Paulus reported grants from NCI during the conduct of the study. No other disclosures were reported.

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