Concurrent Stereotactic Radiosurgery with Antibody-drug Conjugate Treatment for Patients with Breast Cancer Brain Metastases

Introduction: A small proportion of patients with breast cancer brain metastases (BCBM) treated with SRS can develop local inflammatory changes consistent with adverse radiation effect (ARE). In the era of targeted therapies, antibody drug conjugates (ADCs) have been used more frequently and demonstrated significant intracranial efficacy. Therefore, we sought to investigate whether SRS with concurrent ADC therapy may be associated with increased risk of symptomatic ARE.

Methods: We used our prospective patient registry to evaluate data from 2012-2023. Adverse radiation effects (AREs) were determined via radiographic follow-up. Peritumoral patchy enhancement with a mismatch on the long relaxation time images was coded as an inflammatory change consistent with ARE. Concurrent use of ADC was noted if SRS was done 7 days before or 30 days after ADC delivery. A competing risk analysis with the Fine and Gray method was conducted.

Results: In total, 46 patients with 290 tumors and a median age of 56.5 (IQR, 48-63) were included. The median follow-up time was 23 months (IQR, 15-42) and a maximum follow up of 120 months. At the time of analysis, 19 patients (41%) were alive while 22 patients (48%) were deceased due to non-neurologic causes and 5 patients (11%) were deceased due to neurologic causes. Sixteen patients (35%) received whole-brain radiotherapy (WBRT) prior to SRS and ADC treatments. Twenty-seven patients (59%) received ADC concurrently with SRS while 19 patients (41%) received ADC sequentially. The median margin dose was 16 Gy (IQR, 15-18) and the median total tumor volume was 1.8 cm3 (IQR, 0.48-6). The 12 and 24-month cumulative incidence of ARE for the entire cohort were 8% and 10%, respectively. Concurrent ADC was not associated with increased risk of ARE (SHR, 0.024 [95% CI, 0-248]; P=0.428). Amongst the entire cohort, the median number of SRS treatments was 2 (IQR, 2-3).

Conclusion : In our institutional analysis we found no increased risk of symptomatic ARE development with concurrent SRS and ADC. These results should be further validated by prospective multi-institutional studies.