Analysis of Factors Associated With Hemorrhage Post-radiotherapy for Brain Metastasis: A Population-Based Study

Objective: This study aimed to characterize the incidence, risk factors, and symptoms associated with intracranial hemorrhage (ICH) following radiotherapy (RT) for hemorrhage-prone brain metastases (BM).Methods: This retrospective population-based cohort study examined all patients with BM who were treated with RT in British Columbia from 2017 to 2022.Patients were included if their primary cancers were melanoma, colorectal, renal, hepatocellular, head and neck, germ cell, or sarcoma, as such cancers are associated with a higher risk of hemorrhagic BM.Patient comorbidities and the use of blood thinners were recorded.Post-RT ICH was identified through CT or MRI reports.Cumulative incidence curves were compared using Gray's test.Fine and Gray competing risk regression models were used to evaluate factors associated with ICH.Results: A total of 319 patients treated for 943 lesions were identified, with a median follow-up period of 4.3 months.The most common primary cancer site was melanoma (42%).Forty-one patients (13%) developed ICH, with a median time to ICH of 2.5 months.The rates of ICH pre-and post-RT were 25% and 10% at the patient level.At the lesion level, the rates of ICH pre-and post-RT were 16% and 6%, respectively.On patient-level multivariable analysis, focal RT was associated with a higher risk of ICH than whole-brain RT (p = 0.003).Patients with a primary cancer of melanoma were more likely to have ICH than those with primary colorectal cancer (p = 0.008), and those with a history of stroke were more likely to bleed than those with no history of stroke (p = 0.05).Older age was associated with a lower risk of ICH (p = 0.03).Blood thinner use was not associated with ICH.At lesion-level multivariable analysis, focal RT was no longer significantly associated with ICH.Of the 41 patients who developed ICH, 26 (63%) experienced symptoms.The most common symptoms were headache, weakness, and confusion.Conclusions: Post-RT ICH may occur early after treatment, resulting in neurological symptoms and reduced quality of life.RT, prior hemorrhage, and the use of blood thinners were not clearly associated with an increased risk of ICH.Early and vigilant monitoring for ICH may be warranted in patients with melanoma BM.