Associated Factors of Spontaneous Hemorrhage in Brain Metastases in Patients with Lung Adenocarcinoma.

BACKGROUND: Hemorrhage in brain metastases (BMs) from lung cancer is common and associated with a poor prognosis. Research on associated factors of spontaneous hemorrhage in patients with BMs is limited. This study aimed to investigate the predictive risk factors for BM hemorrhage and assess whether hemorrhage affects patient survival. METHODS: We retrospectively evaluated 159 BMs from 80 patients with lung adenocarcinoma from January 2017 to May 2022. Patients were classified into hemorrhagic and non-hemorrhagic groups. Patient demographics, lung cancer molecular subtype, treatment type, and tumor-node-metastasis stage were compared between the groups. Multivariate generalized estimating equation (GEE) analysis and gradient boosting were performed. To determine whether BM hemorrhage can stratify overall survival after BM (OSBM), univariate survival analysis was performed. RESULTS: In the univariate analysis, hemorrhagic BMs were significantly larger and had a history of receiving combination therapy with tyrosine kinase inhibitor (TKI) and intracranial radiation (p < 0.05). Multivariate GEE showed that tumor size and combination therapy were independent risk factors for BM hemorrhage (p < 0.05). Gradient boosting demonstrated that the strongest predictor of BM hemorrhage was tumor size (variable importance: 49.83), followed by age (16.65) and TKI combined with intracranial radiation (13.81). There was no significant difference in OSBM between the two groups (p = 0.33). CONCLUSIONS: Hemorrhage in BMs from lung adenocarcinomas may be associated with BM tumor size and a combination of TKI and intracranial radiotherapy. BM hemorrhage did not affect OSBM.