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Clinical Trial
. 2023 Apr 3;6(4):e238504.
doi: 10.1001/jamanetworkopen.2023.8504.

Association of Radiotherapy Duration With Clinical Outcomes in Patients With Esophageal Cancer Treated in NRG Oncology Trials: A Secondary Analysis of NRG Oncology Randomized Clinical Trials

Christopher L Hallemeier  1 , Jennifer Moughan  2 , Michael G Haddock  1 , Arnold M Herskovic  3 , Bruce D Minsky  4 , Mohan Suntharalingam  5 , Kenneth L Zeitzer  6 , Madhur K Garg  7 , Bruce D Greenwald  8 , Ritsuko U Komaki  4 , Lindsay L Puckett  9 , Hyun Kim  10 , Shane Lloyd  11 , David A Bush  12 , Harold E Kim  13 , Thomas E Lad  14 , Joshua E Meyer  15 , Gordon S Okawara  16 , Adam Raben  17 , Tracey E Schefter  18 , Jerry L Barker Jr  19 , Carla I Falkson  20 , Gregory M M Videtic  21 , Rojymon Jacob  22 , Kathryn A Winter  2 , Christopher H Crane  23
Affiliations
Clinical Trial

Association of Radiotherapy Duration With Clinical Outcomes in Patients With Esophageal Cancer Treated in NRG Oncology Trials: A Secondary Analysis of NRG Oncology Randomized Clinical Trials

Christopher L Hallemeier et al. JAMA Netw Open. .

Abstract

Importance: For many types of epithelial malignant neoplasms that are treated with definitive radiotherapy (RT), treatment prolongation and interruptions have an adverse effect on outcomes.

Objective: To analyze the association between RT duration and outcomes in patients with esophageal cancer who were treated with definitive chemoradiotherapy (CRT).

Design, setting, and participants: This study was an unplanned, post hoc secondary analysis of 3 prospective, multi-institutional phase 3 randomized clinical trials (Radiation Therapy Oncology Group [RTOG] 8501, RTOG 9405, and RTOG 0436) of the National Cancer Institute-sponsored NRG Oncology (formerly the National Surgical Adjuvant Breast and Bowel Project, RTOG, and Gynecologic Oncology Group). Enrolled patients with nonmetastatic esophageal cancer underwent definitive CRT in the trials between 1986 and 2013, with follow-up occurring through 2014. Data analyses were conducted between March 2022 to February 2023.

Exposures: Treatment groups in the trials used standard-dose RT (50 Gy) and concurrent chemotherapy.

Main outcomes and measures: The outcomes were local-regional failure (LRF), distant failure, disease-free survival (DFS), and overall survival (OS). Multivariable models were used to examine the associations between these outcomes and both RT duration and interruptions. Radiotherapy duration was analyzed as a dichotomized variable using an X-Tile software to choose a cut point and its median value as a cut point, as well as a continuous variable.

Results: The analysis included 509 patients (median [IQR] age, 64 [57-70] years; 418 males [82%]; and 376 White individuals [74%]). The median (IQR) follow-up was 4.01 (2.93-4.92) years for surviving patients. The median cut point of RT duration was 39 days or less in 271 patients (53%) vs more than 39 days in 238 patients (47%), and the X-Tile software cut point was 45 days or less in 446 patients (88%) vs more than 45 days in 63 patients (12%). Radiotherapy interruptions occurred in 207 patients (41%). Female (vs male) sex and other (vs White) race and ethnicity were associated with longer RT duration and RT interruptions. In the multivariable models, RT duration longer than 45 days was associated with inferior DFS (hazard ratio [HR], 1.34; 95% CI, 1.01-1.77; P = .04). The HR for OS was 1.33, but the results were not statistically significant (95% CI, 0.99-1.77; P = .05). Radiotherapy duration longer than 39 days (vs ≤39 days) was associated with a higher risk of LRF (HR, 1.32; 95% CI, 1.06-1.65; P = .01). As a continuous variable, RT duration (per 1 week increase) was associated with DFS failure (HR, 1.14; 95% CI, 1.01-1.28; P = .03). The HR for LRF 1.13, but the result was not statistically significant (95% CI, 0.99-1.28; P = .07).

Conclusions and relevance: Results of this study indicated that in patients with esophageal cancer receiving definitive CRT, prolonged RT duration was associated with inferior outcomes; female patients and those with other (vs White) race and ethnicity were more likely to have longer RT duration and experience RT interruptions. Radiotherapy interruptions should be minimized to optimize outcomes.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Herskovic reported holding 6 related patents (investments in patents and prototypes) outside the submitted work. Dr Puckett reported payment or honoraria for lectures, presentations, and speakers bureaus from Accuray to the institution outside the submitted work. Dr Lloyd reported receiving personal fees from the Cancer Study Group outside the submitted work. Dr Lad reported receiving grants from the National Cancer Institute (NCI) during the conduct of the study and outside the submitted work. Dr Meyer reported receiving personal fees from Varian outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Study Flow Diagram
RT indicates radiation therapy; RTOG, Radiation Therapy Oncology Group.
See this image and copyright information in PMC

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