Objective To compare and analyze the efficacy and safety of an overall strategy of immunotherapy combined with chemoradiotherapy in patients with limited-stage small cell lung cancer (LS-SCLC)—including induction immunotherapy plus chemotherapy followed by radiotherapy, with or without consolidation and second-line immunotherapy (ICT+RT)—versus conventional chemoradiotherapy alone (CRT), thereby providing evidence-based support for optimizing the clinical use of immunotherapy in LS-SCLC. Methods A total of 375 patients with LS-SCLC treated between June 2018 and June 2024 were retrospectively included, including 37 patients in the ICT+RT group and 338 in the CRT group. After balancing baseline characteristics such as age, sex, and ECOG performance status using 1:2 propensity score matching (PSM), progression-free survival (PFS) and overall survival (OS) were used as the primary endpoints to compare the efficacy and safety of the two treatment strategies. Notably, substantial treatment heterogeneity existed within the ICT+RT group, including variable induction immunochemotherapy for 2–6 cycles, consolidation immunotherapy after radiotherapy in 32.4% of patients, and second-line immunotherapy after disease progression in 54.1% of patients. Results After PSM, 35 patients in the ICT+RT group and 70 in the CRT group were successfully matched, and baseline characteristics were well balanced between the two groups (all SMDs < 0.1). No significant difference in median PFS was observed between the ICT+RT and CRT groups (13.6 vs. 10.8 months; P = 0.430). However, given the small sample size of the ICT+RT group, statistical power was limited, and a potential PFS benefit could not be excluded. OS was significantly prolonged in the ICT+RT group (median OS not reached vs. 24.3 months; P = 0.009), and the 3-year OS rate was significantly higher than that in the CRT group (56.6%vs. 33.2%). Multivariable analysis showed that the overall strategy of immunotherapy combined with chemoradiotherapy was an independent protective factor for OS (HR = 0.38, 95% CI 0.18–0.81; P = 0.012). In terms of safety, the incidences of grade ≥3 anemia (8.11%vs. 1.18%) and thrombocytopenia (13.51%vs. 2.96%) were significantly higher in the ICT+RT group than in the CRT group (both P < 0.05), whereas the incidences of other adverse events were comparable. Conclusion For patients with LS-SCLC, an overall strategy of immunotherapy combined with chemoradiotherapy (including induction ± consolidation ± second-line immunotherapy) may significantly improve OS; however, this benefit reflects the cumulative effect of multistage immunotherapy exposure and cannot be attributed solely to induction immunochemotherapy followed by radiotherapy. This strategy did not improve PFS and was associated with an increased risk of hematologic toxicity, indicating that closer blood count monitoring is warranted in clinical practice. Given the marked sample size imbalance in the ICT+RT group (n = 37) and the substantial intragroup treatment heterogeneity, these findings require validation in large-scale prospective studies.
Zhao et al. (Thu,) studied this question.
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