Real-World Analysis of the Impact of Radiotherapy on Immunotherapy Efficacy in Non-Small Cell Lung Cancer

SIMPLE SUMMARY: Immunotherapy (IO) and radiotherapy (XRT) are two of the most important treatment modalities in metastatic non-small cell lung cancer. There is data to suggest that XRT can enhance the IO’s efficacy. However, little is known regarding how to best combine them. In this retrospective, single-center study, we analyze data of 453 patients who have received various combinations of XRT and IO, or IO alone, to assess the treatment parameters that correlate with longer overall survival (OS). XRT doses between 30 and 40 Gy correlated with longer overall survival, while XRT doses below 10 Gy, fractions of 4.1 to 8 Gy and XRT to the bone correlated with worse overall survival. These results require validation with prospective studies. ABSTRACT: Background: Immunotherapy (IO) provides a significant benefit for a subgroup of non-small cell lung cancer (NSCLC) patients. Radiotherapy (XRT) might enhance the efficacy of IO. We evaluated the impact of the specifics of XRT treatments on the OS of IO-treated NSCLC patients. Methods: Metastatic NSCLC patients treated with IO were retrospectively identified. Parameters included demographics, tumor characteristics, IO and XRT details. Correlation between the parameters and OS was tested with Cox regression. Results: 453 patients were included. No XRT was given to 167 (36.9%) patients, whereas XRT prior and after IO had 182 (40.2%) and 104 (22.9%) patients, respectively. XRT total doses between 30 and 40 Gy had better overall survival (OS) compared to non-irradiated patients (hazard ratio (HR) 0.5, 95% CI 0.25–1.0, p = 0.049). Worse outcome was seen with total doses ≤ 10 Gy (HR 1.67, 95% 1.13–2.5, p = 0.01), XRT fractions of 4.1–8 Gy (HR 1.48, 95% CI 1.05–2.1, p = 0.027) and XRT to the bone (HR 1.36, 95% CI 1.01–1.8, p = 0.04). Several clinical parameters correlated with OS in the univariate analysis of the IO-treated patients. While, in the multivariate analysis, only ECOG-PS, treatment line, type of IO, albumin and NLR remained statistically significant. Conclusion: Specific doses, fractions and sites of XRT correlated with the OS of IO-treated NSCLC patients in the univariate analysis, although not in the multivariate analysis.