247 - Timing of Intracranial Radiotherapy in Breast Cancer Brain Metastases: A Real-World Survival Analysis
Presenter(s)
M. Munir1, A. Y. Cheema2, A. Mandala3, R. Kotecha1, and M. P. Mehta4; 1Miami Cancer Institute, Baptist Health South Florida, Miami, FL, 2Cleveland Clinic Foundatrion, Cleveland, OH, 3Translational Hematology and Oncology Research Institute, Cleveland Clinic, Cleveland, OH, 4Department of Oncological Sciences, Herbert Wertheim College of Medicine, Florida International University, Miami, FL
Purpose/Objective(s): Brain metastases (BM) from breast cancer (BC) are associated with substantial morbidity due to rapid intracranial progression, yet the direct impact of BM control on overall survival (OS) remains unclear. In the modern era of CNS-active therapy, radiotherapy (RT) is often deferred in favor of systemic treatment alone. Despite the potential importance of RT timing, large-scale real-world data evaluating the effect of early versus delayed RT on mortality in BC patients with BM are limited. We examined the association between upfront RT (within three months of BM diagnosis) and clinical outcomes using a global federated electronic health record database.
Materials/Methods: We conducted a retrospective, 1:1 propensity score–matched (PSM) cohort study using the TriNetX Analytics Network database of BMBC patients receiving upfront RT (n=7,914) vs. not (n=7,914) from 2000-2023. PSM was applied using a greedy nearest-neighbor method with a caliper of 0.1 pooled standard deviations, adjusting for demographics, breast cancer subtypes using ICD-10 CM codes (but not molecular subtyping), systemic anticancer therapies, comorbidities, and concomitant medications. The primary outcome was all-cause mortality within one year of BM diagnosis. Secondary outcomes included ischemic stroke or transient ischemic attack (TIA), venous thromboembolism (VTE), hospital admissions, intensive care unit (ICU) admissions, non-traumatic intracranial hemorrhage (ICH), seizures, and cerebral edema (CE). Outcomes were compared using odds ratios (ORs) with 95% confidence intervals (CIs) over a 1-year follow-up period
Results: After PSM, 15,828 patients were included in the analysis (upfront RT: n=7,914; no/delayed RT: n=7,914), with a median age at index of 60 years and >99% females. Compared with patients who did not receive upfront RT, those treated with early RT demonstrated a significantly lower risk of all-cause mortality at 1 year (OR 0.586, 95% CI 0.548,0.627, p<0.001), with a higher survival probability at the end of follow-up (70.8% vs 54.9%). Early RT was also associated with a reduced risk of ischemic stroke or TIA (OR 0.841, 95% CI 0.740,0.956, p=0.008). However, upfront RT was associated with higher odds of VTE (OR 1.096, 95% CI 1.005,1.195, p=0.038), ICU admission (OR 1.244, 95% CI 1.141,1.356, p<0.001), seizures (OR 1.211, 95% CI 1.104,1.329, p<0.001), and CE (OR 1.631, 95% CI 1.509,1.764, p<0.001). No statistically significant differences were observed in the risks of non-traumatic ICH between the two cohorts
Conclusion: In this large real-world, PSM analysis, early intracranial RT in BC patients with BM was associated with a meaningful reduction in short-term mortality, supporting the importance of timely intervention rather than delayed treatment. Prospective studies are warranted to further define the optimal timing, patient selection, and supportive care measures that maximize the survival benefit of upfront RT while mitigating treatment-associated morbidity.