Non-Response to Durvalumab and Supraclavicular Nodal Involvement Predict Early Brain Metastasis After CCRT Followed by Durvalumab Consolidation in Stage III NSCLC.

[PURPOSE] To identify predictors of brain metastasis in patients with unresectable stage III non-small cell lung cancer (NSCLC) treated with definitive concurrent chemoradiotherapy (CCRT) followed by durvalumab consolidation.

[MATERIALS AND METHODS] We retrospectively analyzed 138 patients with unresectable stage III NSCLC treated with definitive CCRT followed by durvalumab from 2018 to 2024. The primary endpoint was brain metastasis incidence. Univariate and multivariate logistic regression analyses identified factors associated with brain metastasis development.

[RESULTS] With a median follow-up of 18.7 months (range, 1.2-73.3), brain metastasis occurred in 18 of 138 patients (13.0%). In multivariate analysis, non-responders to durvalumab (OR 4.86, 95% CI 1.69-13.96, p=0.003) and initial supraclavicular nodal (SCN) involvement (OR 2.89, 95% CI 0.99-8.48, p=0.05) were independent predictors of brain metastasis. Non-responders demonstrated accelerated central nervous system (CNS) progression, with 63.6% developing brain metastases within 6 months versus 28.6% in responders. PD-L1 ≥50% was associated with improved OS but not with brain metastasis incidence. All patients who developed brain metastases were EGFR/ALK wild-type.

[CONCLUSION] Non-responders to durvalumab and supraclavicular nodal involvement were significant predictors of brain metastasis in NSCLC treated with CCRT followed by durvalumab. These findings support risk-adapted CNS surveillance strategies in high-risk patients.