Role of Thoracic Radiotherapy in Extensive Stage Small Cell Lung Cancer (ES-SCLC) in the Immunotherapy Era: A National Hospital-Based Registry Analysis

Abstract

Immunotherapy has shaped the treatment for a number of metastatic cancer types. Based on IMPower 133 and CASPIAN results, chemoimmunotherapy has become standard of care for de-novo ES-SCLC, with increase in median survival of approximately 2-3 months compared to prior standard of care platinum-based doublet therapy with etoposide. However, neither of these trials allowed consolidative thoracic radiotherapy (TRT). Prior to chemo-immunotherapy trials, addition of consolidative TRT to standard chemotherapy improved 2 years survival in patients with any response to chemotherapy. At present, there is no prospective data of role of TRT in ES-SCLC with chemoimmunotherapy. We undertook this study to examine any benefit of TRT in patients with ES-SCLC who received chemoimmunotherapy.We queried the National Cancer Database (NCDB) for patients with ES-SCLC between the ages of 18-90 years treated between 2012-2017 treated with combination of chemotherapy and immunotherapy at the time of diagnosis, and with and without TRT. We excluded patients with unknown treatment status or follow-up time. Overall survival was estimated using Kaplan-Meier method and compared between treatment groups utilizing log-rank testing. An optimal-full propensity-score match was performed utilizing clinical and demographic covariates to reduce the impact of potential confounders of overall survival on the probability of receipt of TRT. Cox proportional hazards regression was used to identify predictors of overall survival.A total of 244 patients were identified meeting selection criteria, treated between 2012 and 2016. There were 63 patients that received TRT and 181 patients that did not. The median age was 65 (40-90) years. The median follow-up was 9.68 (range 0.7-48.3) months. After propensity score matching by age, gender, race, comorbidity score, and type of chemotherapy, there was a trend towards improved median survival from 9 to 11 months and 2 year OS at 18.1% with the addition of TRT vs 12.0% with chemoimmunotherapy alone (P = 0.067). On multivariable analysis only female gender was significantly associated with improved OS after adjustment for age, race, comorbidity score, gender, and receipt of TRT (HR = 0.67 (95% CI 0.51 - 0.89), P = 0.01).In patients with ES-SCLC, the addition of TRT to chemoimmunotherapy is associated with a trend towards improved median and 2 year OS on the order of magnitude of the addition of immunotherapy to chemotherapy as reported in recent trials, though this was not statistically significant in the context of a limited sample size from a non-randomized cohort. Data from prospective, randomized trials are needed to help identify which patients may benefit from TRT in the immunotherapy era.