Abstract

Thoracic radiation (TRT) benefits local control undoubtedly and survival with some minor controversy in extensive-stage small-cell lung cancer (ES-SCLC) patients undergoing radiotherapy in the chemoradiotherapy era. However, whether TRT could further enhance the benefit of immune checkpoint inhibitors (ICIs) maintenance on outcomes in the immunotherapy era is still unclear. This study aims to investigate the role of consolidative TRT in ES-SCLC patients receiving first-line chemoimmunotherapy followed by immunotherapy maintenance. Outcomes of patients who were treated with first-line chemo-immunotherapy followed by ICIs maintenance for ES-SCLC were reviewed. Based on TRT or not, patients were allocated to TRT group or non-TRT group. Progression-free survival (PFS), overall survival (OS) and local-recurrence free survival (LRFS) were calculated by the Kaplan-Meier method and compared by log-rank test. A total of 100 patients with no progressive disease after 4 cycles of chemotherapy were retrospectively analyzed between January 2020 and December 2021 and were allocated into TRT group (n = 47) and non-TRT group (n = 53). The median follow-up time was 20.3 months. The median PFS and OS in TRT were 9.1 months and 21.8 months, versus 8.8 months (p = 0.93) and 24.3 months (p = 0.63), respectively, in non-TRT. ICIs agents consisted of Durvalumab (59.0%) and Atezolizumab (41.0%). The median dose of TRT is 50 Gy (IQR: 45 - 54), while the median interval time from chemotherapy completion to TRT was 31 days (IQR: 12 - 44.5). Only 10 (21.3%) patients terminated ICIs in the period of TRT. The rate of intrathoracic progression after the first-line therapy in TRT significantly decreased compared to that with non-TRT (20.0% versus 55.9%, p = 0.003). The median LRFS time in TRT was not reached, but significantly longer than 10.8 months in non-TRT (HR = 0.27, p < 0.01). Second-line chemotherapy significantly prolonged survival compared to that with chemo-free patients (mOS: 24.5 vs. 21.4 months, p = 0.026). The subgroup analysis showed a trend of patients with brain metastases benefit from TRT (21.8 versus 13.7 months, HR 0.61, p = 0.38) while liver metastases did not (13.3 versus 15.0 months, HR 1.80, p = 0.21). Of 47 patients with TRT, only 10.6% of patients experienced grade 3 radiation-induced pneumonitis, while no grade 4 or 5 adverse events occurred. None of patients experienced grade ≥ 3 treatment-related cardiac events. Consolidative TRT in the period of immunotherapy maintenance followed first-line chemo-immunotherapy did not prolong OS and PFS but increased LRFS in ES-SCLC.

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