Efficacy and safety of omitting the clinical target volume in limited-stage small cell lung cancer: a large-scale multicenter real-world study.

Abstract

Routine Clinical Target Volume (CTV) coverage in limited-stage small cell lung cancer (LS-SCLC) aims to address microscopic extension but often increases toxicity without necessarily translating to improved disease control. Our objective was to determine whether omitting the CTV could preserve efficacy while reducing toxicity compared with conventional delineation, with exploratory contemporary immunotherapy subgroup analysis. This study enrolled 946 LS-SCLC patients between February 2016 and February 2025. According to radiotherapy strategy, patients were classified into an Omit-CTV (n = 403) group and a CTV group (n = 543). Subsequently, propensity score matching yielded 265 patients per group for the final analysis. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included first-failure patterns and treatment-related toxicity. With a median follow-up of 33.2 months, response rates were similar between groups (ORR: 69.4% with CTV vs. 72.8% with Omit-CTV). Median PFS was 11.6 months in the CTV group versus 11.8 months in the Omit-CTV group (HR, 0.93; 95% CI, 0.76-1.14; P = 0.500), while median OS was 30.7 months and 35.8 months, respectively (HR, 0.85; 95% CI, 0.66-1.10; P = 0.220). Furthermore, no statistically significant difference was observed in local recurrence patterns (P = 0.561). Omit-CTV was associated with lower rates of radiation pneumonitis (Grade 1-2: 20.0% vs. 27.2%; Grade ≥ 3: 3.4% vs. 8.3%; P = 0.004) and esophagitis (Grade 1-2: 32.1% vs. 39.2%; Grade ≥ 3: 5.7% vs. 9.1%; P = 0.037). Among patients receiving immunotherapy, median PFS was not reached in the Omit-CTV group and 15.2 months in the CTV group (HR, 0.48; 95% CI, 0.24-0.96; P = 0.033), and median OS was not reached and 26.9 months, respectively (HR, 0.31; 95% CI, 0.11-0.85; P = 0.018). In this large-scale LS-SCLC cohort, Omit-CTV was associated with similar efficacy and lower rates of treatment-related toxicity, with a promising survival signal in patients receiving immunotherapy, warranting further prospective validation.