NCTQ-01 RISK OF RADIATION NECROSIS FOLLOWING CONCURRENT VERSUS SEQUENTIAL ADMINISTRATION OF ANTIBODY-DRUG CONJUGATES AND STEREOTACTIC RADIOSURGERY (SRS) IN PATIENTS WITH METASTATIC BREAST CANCER AND BRAIN METASTASES

Abstract BACKGROUND The risk of radiation necrosis (RN) among patients with metastatic breast cancer (MBC) and brain metastases (BrM) treated with SRS alongside antibody-drug conjugates (ADCs) requires further study. METHODS A single-centre retrospective cohort study to assess the incidence of RN among women with MBC treated with SRS for BrM at the Sunnybrook Odette Cancer Centre from 2004-2024. ADC delivered ≤4 weeks before or after SRS was labelled as concurrent; ADC delivered outside this window was considered sequential. Baseline clinical/pathological and treatment-related factors were abstracted from patients’ medical records. Clinical and treatment characteristics are described with median and range for continuous variables, or frequencies and percentages for categorical variables. Logistic regression and Cox proportional hazards models were used to investigate factors associated with the development of RN. RESULTS In a database of 1424 patients with breast cancer BrM, 87 (6.1%) received an ADC (T-DXd or T-DM1); 56 (3.9%) patients who received both SRS and an ADC during their disease course formed our cohort. Median age was 60 years (range: 39–85); 50 patients (89%) had HER2+ and 6 patients (11%) had HR+/HER2-low MBC. 22 patients (39%) received an ADC concurrently with SRS and 34 (61%) received an ADC sequentially. Overall, 16 patients (29%) developed RN with the majority being symptomatic (n=11); the incidence of symptomatic RN (SRN) was significantly higher among patients receiving concurrent versus sequential therapy (36% vs 9%; p=0.029). When assessed as continuous variables in univariate analyses, lower equivalent dose in 2 Gy fractions (p<0.001), larger BrM (p<0.001), and lower patient weight (p<0.001) were associated with a higher risk of SRN. Lesion-based analyses are ongoing and will be presented at the meeting. CONCLUSIONS Caution needs to be taken when administering SRS concurrently with an ADC as about a third of patients develop SRN.