Should Radiation Dose Be Personalized in Patients With Localized NSCLC and Actionable Genetic Alterations? Insight From a Multicenter Real-World Study.

Objectives: Radiation therapy (RT) is central to the management of unresectable stage I to III NSCLC. However, the impact of actionable genetic driver alterations (AGAs) on locoregional control (LRC) from RT remains uncertain. A retrospective, multicenter real-world study was undertaken to determine if common AGAs impact LRC after RT.

Methods: Patients who received curative-intent RT for NSCLC between 2018 and 2020 at four centers in the United Kingdom and had available molecular testing were included. Locoregional control was compared in a 1:2 ratio between a group of patients with an AGA and a control group without AGAs. Locoregional control was assessed with competing risks analysis and overall survival was analyzed by Cox regression, adjusting for established prognostic clinical factors.

Results: Data was collected for 185 eligible patients: 50 with an AGA and 135 without. Baseline characteristics, including patient demographics, tumor features, and treatment details were evenly distributed between the two groups. LRC was similar in the AGA and non-AGA groups (39% versus 34%, hazard ratio = 1.13, 95% confidence interval: 0.61-1.984,  = 0.84). Actionable genetic driver alterations were not associated with LRC according to multivariable regression analysis. Median overall survival was significantly higher in the AGA group (45 mo versus 26 mo, hazard ratio = 0.64, 95% confidence interval: 0.43-0.96,  = 0.044), and all these patients received targeted therapies on relapse.

Conclusion: LRC was comparable in the AGA and non-AGA groups suggesting that there is no role for personalization of RT dose solely due to the detection of an AGA. Nevertheless, survival rates were notably higher among patients with AGAs, likely owing to the availability of efficacious targeted therapies on relapse.