Risk-based local radiotherapy in oligometastatic NSCLC in the era of immunotherapy: a multi-centric cohort study

Jinghao Duan; Yingming Zhu; Wei Jiang; Wenqing Wang; Ying Jiang; Huiyao Huang; Jianzhong Cao; Nan Bi

doi:10.1016/j.ijrobp.2025.06.3857

Risk-based local radiotherapy in oligometastatic NSCLC in the era of immunotherapy: a multi-centric cohort study

Int J Radiat Oncol Biol Phys. 2025 Jun 25:S0360-3016(25)04499-2. doi: 10.1016/j.ijrobp.2025.06.3857. Online ahead of print.

Authors

Jinghao Duan¹, Yingming Zhu¹, Wei Jiang², Wenqing Wang¹, Ying Jiang¹, Huiyao Huang³, Jianzhong Cao⁴, Nan Bi⁵

Affiliations

¹ Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
² Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China.
³ Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. Electronic address: huanghy314@sina.cn.
⁴ Department of Radiation Oncology, Shanxi Cancer Hospital and the Affiliated Cancer Hospital of Shanxi Medical University, Taiyuan, China. Electronic address: caolv2000@163.com.
⁵ Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. Electronic address: binan_email@163.com.

PMID: 40578452
DOI: 10.1016/j.ijrobp.2025.06.3857

Abstract

Background: The role of consolidation radiotherapy (cRT) in patients with oligometastatic non-small-cell lung cancer (oligo-NSCLC) without driver genetic alterations remains uncertain in the era of immunotherapy (IO). This study aimed to evaluate the efficacy of cRT combined with IO at various programmed death ligand 1 (PD-L1) expression levels using data from a multicenter cohort.

Methods: Patients with oligo-NSCLC without driver genetic alterations, treated with IO with or without cRT, and with available PD-L1 tumor proportion scores (TPS) were retrospectively reviewed across three institutions. Inverse probability of treatment weighting (IPTW) was applied to control for bias.

Results: This study included 240 patients, among which 30·4%, 35·0%, and 34·6% patients had PD-L1 TPS 0, 1-49% and ≥ 50%, respectively. After IPTW adjustment, subgroup analysis revealed that cRT significantly improved progression-free and overall survival in the PD-L1 TPS 0-49% group (HR: 0·59; 95% CI: 0·38-0·92; P = 0·009; HR: 0·59; 95% CI: 0·35-0·99; P = 0·016; respectively), however, no additional benefit was found in the PD-L1 TPS ≥ 50% group. Multivariate Cox analysis identified PD-L1 TPS score as an independent prognostic factor only in the IO group (HR: 0·54; 95% CI: 0·34-0·88; P = 0·01). Adding cRT to IO in patients with PD-L1 TPS 0-49% improved survival to levels comparable to those of patients with PD-L1 TPS ≥ 50%. Moreover, cRT was associated with lower rate of progression at original sites in the overall cohort (HR: 0·51; 95% CI: 0·32-0·81, P = 0·005), particularly in the PD-L1 TPS 0-49% subgroup (HR: 0·38; 95%: CI 0·21-0·68; P = 0·001).

Conclusions: The addition of cRT to IO may improve survival outcomes for driver-negative oligometastatic NSCLC patients with low or negative PD-L1 expression. The PD-L1 TPS may be a valuable biomarker to optimize cRT patient selection in the era of immunotherapy. Further prospective investigations into this stratification strategy are warranted.

Keywords: Consolidation radiotherapy; Oligometastatic NSCLC; PD-L1 TPS; Survival outcomes; immunotherapy.