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Clinical Trial
. 2021 Oct 1;7(10):1497-1505.
doi: 10.1001/jamaoncol.2021.3186.

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

Puneeth Iyengar  1   2   3 , Elizabeth Zhang-Velten  1   2   3 , Laurence Court  4 , Kenneth Westover  1   2   3 , Yulong Yan  1   2   3 , Mu-Han Lin  1   2   3 , Zhenyu Xiong  1   2   3 , Mehul Patel  5 , Douglas Rivera  6 , Joe Chang  4 , Mark Saunders  7 , Anand Shivnani  8 , Andrew Lee  9 , Randall Hughes  1   2   3 , David Gerber  1   2   3 , Jonathan Dowell  1   2   3 , Ang Gao  1   2   3 , John Heinzerling  10 , Ying Li  11 , Chul Ahn  1   2   3 , Hak Choy  1   2   3 , Robert Timmerman  1   2   3
Affiliations
Clinical Trial

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

Puneeth Iyengar et al. JAMA Oncol. .

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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Conflict of interest statement

Conflict of Interest Disclosures: Dr Iyengar reported serving on the advisory board of AstraZeneca plc outside the submitted work. Dr Westover reported receiving personal fees from Vibliome Therapeutics, LLC, for participation in the scientific advisory board and grants from Revolution Medicines, Inc, outside the submitted work. Dr Chang reported receiving grants from Bristol Myers Squibb and personal fees from Varian Medical Systems, Legion Healthcare Partners, and AstraZeneca plc outside the submitted work. Dr Dowell reported receiving personal fees from AstraZeneca plc, Genentech, Inc, and Boehringer Ingelheim 1-time advisory board outside the submitted work. Dr Heinzerling reported receiving grants from AstraZeneca plc and Vision RT outside the submitted work. Dr Timmerman reported receiving grants from Varian Medical Systems, Elekta, and Accuray Incorporated to his institution as a principal investigator outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. CONSORT Diagram of Trial Patients
CFRT indicates conventionally fractionated radiotherapy; IGRT, image-guided radiotherapy.
Figure 2.
Figure 2.. Study Outcomes
A, Median overall survival was 8.2 (95% CI, 5.4-12.4) months in the hypofractionated image-guided radiotherapy (IGRT) group vs 10.6 (95% CI, 8.4-15.3) months in the conventionally fractionated radiotherapy (CFRT) group (P = .17). B, Median progression-free survival was 6.4 (95% CI, 4.1-7.8) months in the hypofractionated IGRT group vs 7.3 (95% CI, 5.0-10.6) months in the CFRT group (P = .77). C, Neither group reached median time to local relapse (P = .34). D, Median time to distant metastasis was not reached in the hypofractionated IGRT group vs 18.0 (95% CI, 7.4-36.0) months in the CFRT group (P = .16).
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