Efficacy and Toxicity of Moderately Hypofractionated Radiotherapy with Helical TomoTherapy versus Conventional Radiotherapy in Patients with Unresectable Stage III Non–Small-Cell Lung Cancer Receiving Concurrent Chemotherapy: A Multicentre, Randomized Phase III Trial

Purpose The standard treatment schedule for unresectable stage III non–small-cell lung cancer (NSCLC) is chemotherapy with concurrent radiotherapy (60 Gy delivered in 30 fractions), although moderately hypofractionated radiotherapy (Hypo-RT) has also been considered as an alternative strategy. This study aimed to compare the efficacy and toxicity of moderately Hypo-RT with helical TomoTherapy versus conventionally fractionated radiotherapy (Con-RT) in patients with unresectable stage III NSCLC receiving concurrent chemotherapy. Methods and Materials In this randomized multicentre non-blinded phase III clinical trial, eligible patients were randomized at a 1:1 ratio to either the Hypo-RT group, (60 Gy in 20 fractions) or to the Con-RT group (60 Gy in 30 fractions). All patients received two cycles of concurrent platinum-based chemotherapy plus two cycles of consolidation therapy. The primary endpoint was 3-year overall survival (OS) in the intention-to-treat population. The secondary endpoints were progression-free survival (PFS) and treatment-related adverse events. Results A total of 146 patients were enrolled from July 27, 2018 to November 1, 2021. The median follow-up was 46 months. The 3-year OS rates in the Hypo-RT and the Con-RT groups were 58.4% and 38.4%, respectively (P = 0.02). The median OS from randomization was 41 months in the Hypo-RT group and 30 months in the Con-RT group (hazard ratio, 0.61; 95% confidence interval, 0.40–0.94; P = 0.02). There was no significant difference in the rates of grade ≥2 treatment-related adverse events between the two groups. Conclusions Moderately Hypo-RT using helical TomoTherapy may improve OS in patients with unresectable stage III NSCLC while maintaining toxicity rates. TRIAL REGISTRATION Chinese Clinical Trial Registry ChiCTR1800017367