# Timing, fractionation, and dose of thoracic radiotherapy in patients with extensive-stage small cell lung cancer undergoing first-line Chemo-Immunotherapy

## TL;DR

This study finds that sequential thoracic radiotherapy after chemoimmunotherapy improves survival and reduces toxicity in extensive-stage small cell lung cancer patients.

## Contribution

The study identifies sequential TRT as superior to concurrent TRT and highlights tBED as a key factor in treatment outcomes.

## Key findings

- Sequential TRT after chemoimmunotherapy improved progression-free and overall survival compared to concurrent TRT.
- Lower time-corrected biological effective dose (tBED) was linked to better outcomes in concurrent TRT.
- Age, KPS, tBED, and metastasis status were identified as independent prognostic factors.

## Abstract

•The optimal thoracic RT timing for ES-SCLC is controversial. We evaluated early RT, which failed to improve survival but increased toxicity.•RT dose and fractionation impact ES-SCLC outcomes, affecting tumor control and quality of life. We performed an exploratory analysis.•Safety is critical in ES-SCLC. We explored toxicity-related factors during TRT to inform individualized clinical management.•This study identified independent prognostic factors for ES-SCLC patients receiving TRT, enabling early and precise outcome prediction.

The optimal thoracic RT timing for ES-SCLC is controversial. We evaluated early RT, which failed to improve survival but increased toxicity.

RT dose and fractionation impact ES-SCLC outcomes, affecting tumor control and quality of life. We performed an exploratory analysis.

Safety is critical in ES-SCLC. We explored toxicity-related factors during TRT to inform individualized clinical management.

This study identified independent prognostic factors for ES-SCLC patients receiving TRT, enabling early and precise outcome prediction.

This study investigates the optimal timing, fractionation, and dose of thoracic radiotherapy (RT) in extensive-stage small cell lung cancer (ES-SCLC) patients responsive to first-line Chemo-Immunotherapy (CIT), and evaluates efficacy and safety.

In this multicenter retrospective analysis, 280 ES-SCLC patients receiving both CIT and TRT between January 2020 and July 2024 were included. Patients were stratified by TRT timing into Concurrent Chemo-Immuno-Radiotherapy (CCIRT, during CIT) or Sequential CIRT (SCIRT, after CIT) groups. We also evaluated the differences among various prescribed radiation doses and fractionation regimens. To avoid selection bias, we conducted Propensity Score Matching (PSM) for patients. Overall survival (OS), progression-free survival (PFS), and treatment-related adverse events (TRAEs) were assessed and compared.

The median PFS and OS in the study were 8.7 months and 20.6 months, respectively. The SCIRT group demonstrated superior PFS (p = 0.008) and OS (p = 0.048) compared with the CCIRT group, and additionally with a lower incidence of TRAEs. In the CCIRT group, a low time-corrected biological effective dose (tBED) (≤50 Gy) was associated with better OS (p = 0.028) and PFS (p = 0.014). Sex, KPS, tBED, brain metastasis status, and other indicators were independent influencing factors for TRAEs. Age, KPS, tBED, and distant metastasis status were independent prognostic factors.

Based on the efficacy and safety profile, sequential TRT after first-line chemoimmunotherapy is superior to concurrent administration. The exploratory conclusions regarding the optimal dose and fractionation regimen require confirmation through further research.