Outcomes and risk factors of hemorrhage in patients with resected brain metastases

Brain metastases (BrMs) may present with intralesional or intracranial hemorrhage (ICH), yet risk factors and outcomes remain unclear. This monocentric cohort study at Germany's largest neurosurgical clinic included 973 adults undergoing BrM resection (2010-2024), with histopathologically confirmed etiologies and known tumor burden. Based on pre-operative CT or MRI, 880 patients were categorized as non-hemorrhagic (non-hBrM), presenting with intralesional hemorrhage (hBrM), or with ICH of ≥30 mm diameter (ICH-BrM). Risk factors for hBrM and ICH-BrM were assessed, and overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meyer methods. Of 880 patients, 560 (63.6%) were non-hBrM, 243 (27.6%) hBrM, and 77 (8.8%) ICH-BrM. ICH-BrM had larger tumor volume (21 cm³, IQR 13-34) than hBrM (14 cm³, IQR 6-28) and non-hBrM (12 cm³, IQR 6-21) (p_adjust = .017), correlated with lower post-op Karnofsky index (p_adjust = .047), dsGPA score (p_adjust = .032), and more BrMs (p_adjust = .004). Pre-operative antithrombotic use did not differ between groups (p_adjust = .32). Melanoma was more common in hBrM (27.8%) and ICH-BrM (38.0%), predicting ICH (OR 2.95, p < .001) along with NSCLC (OR 1.64, p < .001). ICH did not independently predict worse OS (HR 1.23, p = .38). Worse OS was linked to larger tumor volume (HR 1.35, p = .002), extracranial metastases (HR 1.77, p < .001), and older age (HR 1.53, p < .001), while KPS >80% (HR 0.77, p < .01), solitary BrM (HR 0.62, p = .002), and adjuvant treatments (p < .001) predicted improved OS. ICH is associated with larger tumors and melanoma but is not an independent OS predictor. Tumor burden, extracranial metastases, and adjuvant treatments drive BrM survival.