Stereotactic versus whole-brain radiotherapy combined with immunotherapy in driver gene–negative NSCLC with brain metastases: a real-world IPTW analysis

By
Erha Munai
Lisi Sun
Amu Jike
Dan Tao
Nan Li
Jiang He
Yu He
Liang Du
Wei Zhou
Yongzhong Wu
Dingyi Yang
June 22, 2026
0 min

Frontiers In Immunology

Overview

This study evaluates the efficacy and safety of stereotactic radiotherapy (SRT) plus immunotherapy versus whole-brain radiotherapy (WBRT) plus immunotherapy in patients with driver gene-negative non-small cell lung cancer (NSCLC) and brain metastases.

Background

Brain metastases are a common complication in non-small cell lung cancer (NSCLC) and are associated with poor prognosis. The integration of immune checkpoint inhibitors with radiotherapy presents a new treatment avenue, yet comparative studies between WBRT and SRT are lacking.

Data Highlights

Outcome	SRT+I	WBRT+I	P-value
Median Overall Survival	29.3 months	19.9 months	0.034
Intracranial Progression-Free Survival	14.7 months	9.4 months	0.038
Intracranial Objective Response Rate	78.6%	61.5%	N/A
Intracranial Disease Control Rate	95.0%	88.5%	N/A
Radiation-Induced Brain Injury	3.75%	10.26%	N/A

Key Findings

SRT+I resulted in a median overall survival of 29.3 months compared to 19.9 months for WBRT+I (P = 0.034).
Intracranial progression-free survival was significantly longer in the SRT+I group (14.7 months) than in the WBRT+I group (9.4 months, P = 0.038).
The intracranial objective response rate was higher in the SRT+I group (78.6%) compared to the WBRT+I group (61.5%).
The disease control rate was also superior in the SRT+I group (95.0%) compared to the WBRT+I group (88.5%).
Radiation-induced brain injury occurred less frequently in the SRT+I group (3.75%) than in the WBRT+I group (10.26%).
No grade ≥3 immune-related adverse events were reported in the SRT+I group.

Clinical Implications

The findings provide data on survival outcomes and toxicity for SRT combined with immunotherapy versus WBRT with immunotherapy in patients with driver gene-negative NSCLC and brain metastases.

Conclusion

SRT+I demonstrates efficacy in terms of survival and disease control compared to WBRT+I for patients with driver-gene-negative NSCLC and brain metastases.