ESTRO 2025 - Abstract Book

S733

Clinical - CNS

ESTRO 2025

3808

Digital Poster Clinical outcomes in patients with HER2-positive Breast Cancer Brain Metastases treated with Stereotactic Radiosurgery Eva Ruane, Guhan Rangaswamy, Christina Skourou, Bahareh Khosravi, Nazmy Elbeltagi, David Fitzpatrick, Clare Faul St Luke's Hospital, St Luke's Radiation Oncology Network, Dublin, Ireland Purpose/Objective: Metastatic HER2-positive Breast Cancers carry a 30-40% risk of brain metastases (BM). Stereotactic radiosurgery (SRS) offers excellent local control with lower neurocognitive toxicity than whole-brain radiotherapy (WBRT). Up to three-fold higher rates of local progression after brain RT for HER2+ than luminal tumours are described. Rates of symptomatic radiation necrosis (RN) up to 37% are reported with concurrent HER2-targeted therapies. We report on our institutional experience of SRS to HER2+ BM. Material/Methods: We collected data on patients with HER2-positive BM treated with SRS or VMAT (Volumetric Modulated Arc Therapy) SRS between 2017 and 2024. Survival endpoints and predictors of radiation necrosis (RN) were analysed using Kaplan-Meier survival curves and Cox regression. Results: Fifty-one patients were treated. A total of 122 lesions including 27 resection cavities were treated. Ten lesions were treated with VMAT/SRS where the gross tumour volume (GTV) was >20cc. Median time from primary diagnosis to BM was 2.8 years. Thirty-two patients had extra-cranial disease and 31 patients were on systemic therapy (SACT) at time of SRS. Median overall survival (OS) from RT was 2.6 years with 70% patients surviving 1 year. Thirty-one patients experienced intracranial progression (ICP). Median time to ICP was 13 months with 86% freedom from local recurrence at 1 year. Twenty patients with ICP underwent re-irradiation. Patients with a diagnosis of BM < 2 years of primary diagnosis had a worse OS than those diagnosis > 2 years – 1.5 vs 3.5 years (p = 0.009). Absence of extra cranial disease was associated with worse OS than presence of extra-cranial disease - 1.2 vs 2.9 years (p = 0.05). This was possibly skewed by proportion of patients without extra-cranial disease who developed leptomeningeal disease (6 vs 1). No significant association was seen between age, ER status, GTV or number of metastases on OS or ICP. Sixteen patients (37%) developed RN and 6 (14%) were symptomatic. No significant association was seen between RN and SACT use or previous/salvage WBRT. Conclusion: Clinical outcomes for HER2-positive BM treated with SRS/VMAT at our institution align with reported literature, showing high local control rates. Stratifying patients by biological behaviour, such as time from primary diagnosis, may help individualise treatment. Newer systemic agents achieving intracranial control suggest a subset of patients with small-volume BM and aggressive extra-cranial disease may benefit from first-line SACT. Optimising radiotherapy to enhance local control and minimise symptomatic RN remains crucial for this cohort with favourable long-term outcomes. References: Ippolito, Edy et al. “Radiotherapy for HER 2 Positive Brain Metastases: Urgent Need for a Paradigm Shift.” Cancers vol. 14,6 1514. 15 Mar. 2022, doi:10.3390/cancers14061514 Cagney, Daniel N et al. “Breast cancer subtype and intracranial recurrence patterns after brain-directed radiation for brain metastases.” Breast cancer research and treatment vol. 176,1 (2019): 171-179. doi:10.1007/s10549-019-05236-6 Vern-Gross, Tamara Z et al. “Breast cancer subtype affects patterns of failure of brain metastases after treatment with stereotactic radiosurgery.” Journal of neuro-oncology vol. 110,3 (2012): 381-8. doi:10.1007/s11060-012-0976-3 Keywords: SRS, brain metastases, HER2+