Retrospective study on safety and efficacy of hypofractionated versus conventional fractionated sequential radiotherapy for stage III unresectable non-small cell lung cancer.

e20058 Background: Large-scale clinical data directly comparing hypofractionated radiotherapy (HypoRT) with conventional fractionated radiotherapy (ConvRT) in the sequential setting for stage III unresectable non-small cell lung cancer (NSCLC) are lacking. This study aimed to evaluate whether a 4-week HypoRT regimen is as effective and safe as a 6-week ConvRT regimen. Methods: Large-scale clinical data directly comparing hypofractionated radiotherapy (HypoRT) with conventional fractionated radiotherapy (ConvRT) in the sequential setting for stage III unresectable non-small cell lung cancer (NSCLC) are lacking. This study aimed to evaluate whether a 4-week HypoRT regimen is as effective and safe as a 6-week ConvRT regimen. Results: From October 2018 to December 2024, 280 patients were included and allocated in a 2:1 ratio to the HypoRT group (n = 178) or the ConvRT group (n = 102). Baseline characteristics were balanced. With a median follow-up of 47.2 months, HypoRT did not meet the pre-specified non-inferiority margin for OS compared to ConvRT. Median OS was 51.4 months in the HypoRT group and 44.6 months in the ConvRT group (hazard ratio [HR] = 1.08; 95% confidence interval [CI], 0.78–1.36). The 1-, 2-, 3-, and 5-year OS rates were 90.3%, 72.8%, 58.4%, and 46.5% for HypoRT, and 89.1%, 71.2%, 57.4%, and 45.8% for ConvRT, respectively. Median PFS was similar between groups (19.5 vs. 16.2 months; HR = 1.11; 95% CI, 0.82–1.35; p = 0.68). Regarding safety, the HypoRT group had a significantly higher incidence of grade ≥2 radiation esophagitis (67.6% vs. 22.5%; p < 0.001). No significant differences were observed in the incidence of grade ≥2 radiation pneumonitis (16.5% vs. 18.7%; p > 0.05), grade ≥3 acute hematological toxicity (59.8% vs. 66.5%; p > 0.05), or long-term toxicity profiles. Conclusions: In this retrospective analysis, the 4-week HypoRT regimen (60 Gy/20 F) did not demonstrate statistical non-inferiority in OS compared to the 6.5-week ConvRT regimen (66 Gy/33 F) for stage III unresectable NSCLC treated with sequential chemoradiotherapy. While survival outcomes were numerically similar, HypoRT was associated with a significantly increased risk of grade ≥2 esophagitis. These findings highlight the need for careful patient selection and toxicity management when considering hypofractionated schedules in this setting.