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Original Investigation
August 12, 2021

Accelerated Hypofractionated Image-Guided vs Conventional Radiotherapy for Patients With Stage II/III Non–Small Cell Lung Cancer and Poor Performance Status: A Randomized Clinical Trial

Author Affiliations
  • 1Department of Radiation Oncology, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas
  • 2Department of Medical Oncology, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas
  • 3Department of Biostatistics, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas
  • 4Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas
  • 5Department of Radiation Oncology, Baylor Scott & White Memorial Hospital, Temple, Texas
  • 6Department of Radiation Oncology, Austin Cancer Center, Austin, Texas
  • 7Department of Radiation Oncology, Texas Oncology Tyler, Tyler
  • 8Department of Radiation Oncology, Texas Oncology Sherman, Sherman
  • 9Department of Radiation Oncology, Texas Center for Proton Therapy, Irving
  • 10Department of Radiation Oncology, Levine Cancer Institute, Atrium Heath, Charlotte, North Carolina
  • 11Department of Radiation Oncology, Banner MD Anderson Cancer Center, Gilbert, Arizona
JAMA Oncol. 2021;7(10):1497-1505. doi:10.1001/jamaoncol.2021.3186
Key Points

Question  For patients with stage II/III non–small cell lung cancer (NSCLC) who cannot receive concurrent chemoradiotherapy owing to comorbidities and/or performance status, can hypofractionated image-guided radiotherapy (IGRT) alone be superior to conventionally fractionated radiotherapy (CFRT) with respect to overall survival?

Findings  In this randomized phase 3 clinical trial of 96 patients with NSCLC, hypofractionated IGRT failed to demonstrate an improvement in overall survival compared with CFRT.

Meaning  Additional trials will need to be powered for assessing equivalence between hypofractionated IGRT and CFRT for patients with stage II/III NSCLC who cannot receive concurrent therapies.

Abstract

Importance  A significant subset of patients with stage II/III non–small cell lung cancer (NSCLC) cannot receive standard concurrent chemoradiotherapy owing to the risk of toxic effects outweighing potential benefits. Without concurrent chemotherapy, however, the efficacy of conventional radiotherapy is reduced.

Objective  To determine whether hypofractionated image-guided radiotherapy (IGRT) would improve overall survival in patients with stage II/III NSCLC who could not receive concurrent chemoradiotherapy and therefore were traditionally relegated to receiving only conventionally fractionated radiotherapy (CFRT).

Design, Setting, and Participants  This nonblinded, phase 3 randomized clinical study enrolled 103 patients and analyzed 96 patients with stage II/III NSCLC and Zubrod performance status of at least 2, with greater than 10% weight loss in the previous 6 months, and/or who were ineligible for concurrent chemoradiotherapy after oncology consultation. Enrollment occurred at multiple US institutions. Patients were enrolled from November 13, 2012, to August 28, 2018, with a median follow-up of 8.7 (3.6-19.9) months. Data were analyzed from September 14, 2018, to April 11, 2021.

Interventions  Eligible patients were randomized to hypofractionated IGRT (60 Gy in 15 fractions) vs CFRT (60 Gy in 30 fractions).

Main Outcomes and Measures  The primary end point was 1-year overall survival.

Results  A total of 103 patients (96 of whom were analyzed [63 men (65.6%); mean (SD) age, 71.0 (10.2) years (range, 50-90 years)]) were randomized to hypofractionated IGRT (n = 50) or CFRT (n = 46) when a planned interim analysis suggested futility in reaching the primary end point, and the study was closed to further accrual. There was no statistically significant difference between the treatment groups for 1-year overall survival (37.7% [95% CI, 24.2%-51.0%] for hypofractionated IGRT vs 44.6% [95% CI, 29.9%-58.3%] for CFRT; P = .29). There were also no significant differences in median overall survival, progression-free survival, time to local failure, time to distant metastasis, and toxic effects of grade 3 or greater between the 2 treatment groups.

Conclusions and Relevance  This phase 3 randomized clinical trial found that hypofractionated IGRT (60 Gy in 15 fractions) was not superior to CFRT (60 Gy in 30 fractions) for patients with stage II/III NSCLC ineligible for concurrent chemoradiotherapy. Further studies are needed to verify equivalence between these radiotherapy regimens. Regardless, for well-selected patients with NSCLC (ie, peripheral primary tumors and limited mediastinal/hilar adenopathy), the convenience of hypofractionated radiotherapy regimens may offer an appropriate treatment option.

Trial Registration  ClinicalTrials.gov Identifier: NCT01459497

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