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Background Current standard of care options for HER2+ breast cancer brain metastasis (BCBrM) include radiation therapy, brain permeable systemic therapies, and in select cases, neurosurgical resection. There is a concern that HER2-directed systemic therapies when administered concurrently with stereotactic radiosurgery (SRS) may increase the risk of radiation necrosis (RN). This study explores the impact of timing and type of systemic therapies on the development of RN in patients treated with SRS for HER2+ BCBrM. Methods This was a single-institution, retrospective study including patients ≥18 years of age with HER2+ BCBrM who received SRS between 2013 and 2018 with at least 12-month post-SRS follow-up. Presence of RN was determined at one-year post-SRS. Demographics, radiotherapy parameters, and timing (“during” defined as four weeks before/after SRS) and type of systemic therapy were evaluated. Results Among 46 patients with HER2+ BCBrM who received SRS, 28 (60.9%) developed RN and 18 (39.1%) did not. Age (mean 53.3 vs 50.4 years, respectively), radiotherapy parameters (dose, fraction, CTV, GTV, CI, V12Gy, all p&amp;gt;0.05), and receipt of any type of systemic therapy during SRS (60.7% vs 55.6%, p = 0.97) did not differ between patients who did or did not develop RN. However, patients who developed RN more commonly received more than one line of HER2-directed therapy independent of SRS timing compared to those who did not develop RN (75.0% vs 44.4%, p = 0.08). In fact, a significantly higher proportion of those who developed RN received more than one line of HER2-directed therapy during a given SRS treatment compared to those did not develop RN (35.7% vs 5.6%, p&amp;lt;0.05). Conclusions Patients with HER2+ BCBrM who receive multiple lines of HER2-directed therapy during SRS for BCBrM may be at higher risk of RN. Collectively, this data supports a practice of holding HER2-directed therapy during treatment with SRS if medically acceptable.

neuro-oncology advances

RADI-13. Systemic Therapy Type and Timing Effects on Radiation Necrosis Risk in HER2+ Breast Cancer Brain Metastases Patients Treated with Stereotactic Radiosurgery