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Purpose <p>This study evaluates the efficacy and safety of combining stereotactic radiotherapy (SRT) with immune checkpoint inhibitors (ICIs) and chemotherapy (ChT) for treating brain oligo-metastases (BMs) in driver-gene-negative non-small cell lung cancer (NSCLC).</p> Methods <p>In this retrospective multi-center study, 255 NSCLC patients with 1–3 BMs were categorized into three groups: SRT + ICIs + ChT (<i>n</i> = 100), SRT + ChT (<i>n</i> = 76), and ICIs + ChT (<i>n</i> = 79). Outcomes included overall survival (OS), intracranial progression-free survival (iPFS), progression-free survival (PFS), and intracranial objective response rate (iORR). Propensity score generation and 1:1:1 matching of patients were performed based on the nine covariates for their potential association with survival outcomes.</p> Results <p>In the propensity score-matched cohort (<i>n</i> = 207), the SRT + ICIs + ChT group demonstrated significantly superior iORR (55.2% vs. 32.9%/49.4%, <i>p</i> = 0.012) and survival outcomes (median OS: 24.7 vs. 14.7/17.8 months, <i>p</i> = 0.028; iPFS: 17.0 vs. 7.8/13.0 months, <i>p</i> = 0.0014) compared to SRT + ChT and ICIs + ChT groups. For BMs ≥ 0.5&#xa0;cm³, SRT + ICIs + ChT demonstrated superior OS (25.3 vs. 13.5/18.5 months; <i>p</i> &lt; 0.001), iPFS (18.0 vs. 7.8/11.8 months; <i>p</i> &lt; 0.001), PFS (13.1 vs. 7.4/7.1 months; <i>p</i> &lt; 0.001), and iORR (57.0% vs. 31.7%/35.1%; <i>p</i> = 0.006) compared to SRT + ChT or ICIs + ChT. Symptomatic BM subgroups showed similar trends (OS: 24.7 vs. 14.5/17.1 months; <i>p</i> = 0.003). In patients receiving SRT combined with ICIs and ChT, concurrent therapy (within both 2-week and 4-week interval) demonstrated significantly superior outcomes over sequential therapy, including prolonged OS (31.6 vs. 17.2–17.7 months), iPFS, and PFS, as well as higher iORR (66.1%/67.2% vs. 39.10%/35.6%) and iDCR. No increased incidence of CNS or immune-related adverse events was observed with combination therapy.</p> Conclusions <p>Concurrent SRT-ICI-ChT synergistically enhances survival and intracranial control in driver-gene-negative NSCLC patients with BMs, particularly for symptomatic or larger lesions (≥ 0.5&#xa0;cm³), without elevating toxicity risks. These findings advocate for integrated radiosurgery-immunotherapy approaches in managing NSCLC brain metastases.</p>

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Combined stereotactic radiotherapy and immunotherapy improves survival in driver-gene-negative NSCLC patients with brain oligo-metastases: a multicenter real-world study

  • 期刊论文

  • 发表日期：

    2025年12月18日

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  • Shilan Luo,
  • Rufei Liu,
  • Peng Li,
  • Hongbin Tu,
  • Shuangqing Lu,
  • Jingdan Pang,
  • Lu Meng,
  • Litang Huang,
  • Yingying Wang,
  • Dawei Chen,
  • Xiaomei Gong

摘要

Purpose

This study evaluates the efficacy and safety of combining stereotactic radiotherapy (SRT) with immune checkpoint inhibitors (ICIs) and chemotherapy (ChT) for treating brain oligo-metastases (BMs) in driver-gene-negative non-small cell lung cancer (NSCLC).

Methods

In this retrospective multi-center study, 255 NSCLC patients with 1–3 BMs were categorized into three groups: SRT + ICIs + ChT (n = 100), SRT + ChT (n = 76), and ICIs + ChT (n = 79). Outcomes included overall survival (OS), intracranial progression-free survival (iPFS), progression-free survival (PFS), and intracranial objective response rate (iORR). Propensity score generation and 1:1:1 matching of patients were performed based on the nine covariates for their potential association with survival outcomes.

Results

In the propensity score-matched cohort (n = 207), the SRT + ICIs + ChT group demonstrated significantly superior iORR (55.2% vs. 32.9%/49.4%, p = 0.012) and survival outcomes (median OS: 24.7 vs. 14.7/17.8 months, p = 0.028; iPFS: 17.0 vs. 7.8/13.0 months, p = 0.0014) compared to SRT + ChT and ICIs + ChT groups. For BMs ≥ 0.5 cm³, SRT + ICIs + ChT demonstrated superior OS (25.3 vs. 13.5/18.5 months; p < 0.001), iPFS (18.0 vs. 7.8/11.8 months; p < 0.001), PFS (13.1 vs. 7.4/7.1 months; p < 0.001), and iORR (57.0% vs. 31.7%/35.1%; p = 0.006) compared to SRT + ChT or ICIs + ChT. Symptomatic BM subgroups showed similar trends (OS: 24.7 vs. 14.5/17.1 months; p = 0.003). In patients receiving SRT combined with ICIs and ChT, concurrent therapy (within both 2-week and 4-week interval) demonstrated significantly superior outcomes over sequential therapy, including prolonged OS (31.6 vs. 17.2–17.7 months), iPFS, and PFS, as well as higher iORR (66.1%/67.2% vs. 39.10%/35.6%) and iDCR. No increased incidence of CNS or immune-related adverse events was observed with combination therapy.

Conclusions

Concurrent SRT-ICI-ChT synergistically enhances survival and intracranial control in driver-gene-negative NSCLC patients with BMs, particularly for symptomatic or larger lesions (≥ 0.5 cm³), without elevating toxicity risks. These findings advocate for integrated radiosurgery-immunotherapy approaches in managing NSCLC brain metastases.