Real-world evidence on the efficacy, safety, and biomarkers of immunotherapy combined with radiotherapy in limited-stage small cell lung cancer.

BACKGROUND: For limited-stage small cell lung cancer (LS-SCLC), immunotherapy combined with chemotherapy as induction followed by subsequent radiotherapy is still under clinical investigation. Some patients who receive treatment have undergone radiotherapy following immunochemotherapy in real-world. However, the preliminary efficacy and safety remain unknown. In this study, we will explore a novel treatment approach for LS-SCLC.

METHODS: This study analyzed 32 patients with LS-SCLC treated at Jilin Cancer Hospital between January 2022 and June 2024. Eligible patients received Immune checkpoint inhibitors (ICIs) combined with chemotherapy, followed by sequential or concurrent radiotherapy and maintenance chemo-immunotherapy. Tumor response was evaluated every two cycles per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, with progression-free survival (PFS) and overall survival (OS) as endpoints. Adverse events (AEs) were graded according to National Cancer Institute-Common Terminology Criteria (NCI-CTC) 5.0. Blood samples were collected at baseline and during treatment to assess immune function, neuron-specific enolase (NSE), pro-gastrin-releasing peptide (ProGRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lactic dehydrogenase (LDH).

RESULTS: All patients received a chemotherapy regimen of 4-6 cycles of carboplatin plus etoposide (EC) or cisplatin plus etoposide (EP). In the latest efficacy assessments, 3.1% achieved complete response (CR), 90.6% achieved partial response (PR), 6.3% achieved stable disease (SD), with overall response rate (ORR) of 93.7% and disease control rate (DCR) of 100%. Adverse reactions related to treatment included grade 3/4 myelosuppression occurring in 15.6%, grade 4 thrombocytopenia in 3.12% and radiation pneumonitis in 18.7%. Follow-up through June 2025 showed median PFS of 16.3 months [95% confidence interval (CI): 11.2-21.3] and median OS of 37 months (95% CI: 30.0-44.0) for first-line treatment. The incidence of abnormal baseline immune function was 78.9%, of which 80% presented as immune suppression. PLR demonstrated significant prognostic value: patients with baseline PLR >101.75 had longer PFS. Similarly, at the end of the second cycle or before radiotherapy, patients with PLR >60.1 also showed prolonged PFS. In contrast, dynamic changes in NLR did not demonstrate prognostic significance [hazard ratio (HR) =1.05, 95% CI: 0.32-3.53, P=0.93]. LDH testing suggested that patients with normal baseline LDH had longer PFS than those with elevated levels (18.5 vs. 10.0 months), although the difference was not statistically significant (P=0.15). Notably, in some patients, LDH levels decreased from elevated to normal during treatment, suggesting a potential association with treatment response.

CONCLUSIONS: Chemotherapy combined with ICIs followed by sequential or concurrent radiotherapy is feasible, safe, and effective for LS-SCLC, achieving high short-term response rates and prolonged PFS. PLR strongly predicts PFS, while normal or decreasing LDH indicates favorable treatment response. Elevated NSE and ProGRP show trends toward shorter PFS. These biomarkers can guide prognosis and therapy monitoring, supporting personalized management in LS-SCLC.