Objective:

To explore the efficacy and prognostic risk factors of brain radiotherapy combined with immunotherapy and chemotherapy in driver gene-negative NSCLC patients with brain metastases.

Approach:

• Study Design: Retrospective study including 222 driver gene-negative NSCLC patients with brain metastases, employing IPTW to reduce selection bias.
• Survival Analysis: Survival outcomes evaluated using Kaplan–Meier curves and Cox regression analysis to identify prognostic factors.

Key Findings:

• Median overall survival (mOS) was longer in the RT+CT+ICI group (19.6 months) compared to the RT+CT group (15 months, HR 0.57, 95% CI 0.41–0.79, P < 0.001).
• Multivariable adjustments confirmed prolonged overall survival (HR 0.58, 95% CI 0.41–0.81, P = 0.002) and progression-free survival (HR 0.72, 95% CI 0.53–0.98, P = 0.038) in the RT+CT+ICI group.
• Stereotactic radiosurgery (SRS) was identified as a protective factor for overall survival.
• PD-L1 expression was associated with better progression-free survival and intracranial progression-free survival.

Interpretation:

Brain radiotherapy combined with immunotherapy and chemotherapy is effective for driver gene-negative NSCLC patients with brain metastases.

Limitations:

• Retrospective design may introduce biases.
• Lack of strict PD-L1 level criteria due to historical testing practices.

Conclusion:

The combination of brain radiotherapy with immunotherapy and chemotherapy shows potential in improving outcomes for driver gene-negative NSCLC patients with brain metastases.