Role and modality of combining radiotherapy with immunotherapy in Stage III-IV Unresectable Small Cell Lung Cancer

Abstract Background The combination of radiotherapy and immunotherapy was rarely reported in the management of small cell lung cancer(SCLC). We retrospectively assessed the role and modality of this combination in Stage III-IV unresectable SCLC. Methods We conducted this study in the South Branch of National Cancer Center(Shenzhen, China). Efficacy and safety of immunotherapy combined with radiotherapy were evaluated in III to IV SCLC patients according to AJCC 8th edition. Thereinto, patients received first-line chemo-immunotherapy and sequential thoracic consolidation radiotherapy (TCRT) were further evaluated. Survival and descriptive analyses were performed. Results Between January 1, 2019 and December 31, 2021, 51 patients were included in our analysis. Median follow-up was 28.0 months(95%CI 22.8–33.2). Patients received radiotherapy in treatment course had a prolonged 2-year overall survival(OS). And in the first-line immunotherapy cohort of 27 patients, the addition of TCRT significantly improved 2y-OS(72.22% vs. 13.89%, p = 0.0048), 2y-locoregional recurrence free survival(LRRFS)(90.00% vs 48.00%, p = 0.011), and 2y-distance progression free survival(DPFS)(66.67% vs. 16.67%, p = 0.039). Subgroup analyses showed that TCRT rendered superior outcomes regardless of brain metastases. Dose-escalation(45Gy/15f) and earlier radiotherapy seemed to improve the benefit. Of 70.37%(19/27) patients experienced disease progression in the TCRT evaluation cohort, 63.16%(12/19) patients failed in brain. A tendency toward better OS and superior brain metastases free survival(BMFS) were observed after receiving prophylactic cranial irradiation(PCI). Finally, the most common grade 2 or higher toxic effects were pneumonitis in all patients(11.76% of immune-related vs. 7.84% of radiation related). Conclusion Earlier addition of TCRT to immunotherapy could significantly improve survival and extracranial control for stage IIIA-IVB unresectable SCLC patients, with no increased risk of adverse events. In the era of immunotherapy, PCI may still be a recommended strategy. Further investigation is warranted.