Thoracic Radiotherapy Improves the Outcomes of Extensive Stage Small-Cell Lung Cancer Patients Receiving First-Line Immunotherapy: A Multicenter Retrospective Analysis

Abstract

Platinum-etoposide chemotherapy combined with immune checkpoint inhibitors has been recommended as the first line standard treatment for extensive-stage small-cell lung cancer (ES-SCLC). However, the role of thoracic radiotherapy (TRT) was still unknown for these patients. The aim of this study was to evaluate the efficacy and safety of TRT for ES-SCLC patients receiving first-line immunotherapy and chemotherapy MATERIALS/METHODS: ES-SCLC patients who received 4 to 6 cycles of chemotherapy and immunotherapy as first-line therapy from two hospitals were included in analysis between July 2018 and January 2023. All patients were divided into two groups based on whether receiving TRT or not during the first-line setting. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoint was toxic effects. The Kaplan-Meier method was used to estimate overall survival and progression-free survival. All adverse events were graded by the senior doctors according to the Common Terminology Criteria for Adverse Events version 5.0. A total of 253 patients from two hospitals were enrolled in analysis. The median age was 62 years and most patients were men (83%), and 36% patients were staged T4 and 52% N3. The most common sites of metastasis were brain (32%), liver (32%) and bone (30%). There were 107 patients (42%) receiving TRT and 146 (58%) without TRT. Baseline characteristics were well balanced between the two groups. The median follow-up time was 16.7 months. Statistically significant benefit was observed for patients receiving TRT compared to patients without TRT (median PFS, 10.4 vs 7.3 months, P< 0.001; median OS, 22.2 vs 13.7 months, P = 0.009). In terms of safety, no significant increase of any grade adverse event (AE) (P = 0.115) and grade 3 or 4 AE (P = 0.631) were observed for patients receiving TRT. The most common grade 3 or 4 AE were neutrophil count decreased, white blood cell count decreased, and nausea in the two groups. In the TRT group, the most common grade 1 or 2 AE related to TRT were esophagitis (40%) and pneumonitis (25%). Grade 3 or 4 esophagitis and pneumonitis were 4% and 8%, respectively. Only one patient developed grade 4 toxic effect of pneumonitis leading to radiotherapy withdrawal. No grade 5 adverse event occurred. Addition of TRT showed significant survival benefits and well tolerability in ES-SCLC patients receiving platinum-etoposide chemotherapy and immune checkpoint inhibitors, which could be a feasible first-line treatment strategy for ES-SCLC patients.