2547 - Impact of Concurrent Antibody-Drug Conjugates and Radiotherapy on Symptomatic Radiation Necrosis in Breast Cancer Patients with Brain Metastases: A Multicenter Retrospective Study

Y. Koide¹, N. Nagai^1,2, M. Ito³, S. Adachi⁴, Y. Shindo², T. Aoyama¹, H. Shimizu¹, S. Hashimoto¹, H. Tachibana¹, and T. Kodaira¹; ¹Department of Radiation Oncology, Aichi Cancer Center Hospital, Nagoya, Japan, ²Department of Radiology, Nagoya University Graduate School of Medicine, Nagoya, Japan, ³Department of Radiation Oncology, Fujita Health University School of Medicine, Toyoake, Japan, ⁴Department of Radiology, Aichi Medical University Hospital, Nagakute, Japan

Purpose/Objective(s): We aimed to investigate the impact of concurrent antibody-drug conjugates (ADC) and radiotherapy on symptomatic brain necrosis (SBN) in patients with brain metastases (BM) from breast cancer. Materials/

Methods: This study is a multicenter retrospective design using data from four institutions. Eligibility patients were selected based on the following criteria: (1) histologically proven breast cancer and subtypes; (2) BM was diagnosed with gadolinium-enhanced MRI; (3) a Karnofsky performance status (KPS) score of 60 or higher at the time of the BM diagnosis; and (4) underwent radiotherapy for all BM lesions between 2017 and 2022. Patients with leptomeningeal dissemination were excluded. For this study, concurrent ADC is defined as using ADC within four weeks of the first day of radiotherapy, and trastuzumab deruxtecan (T-DXd) and trastuzumab emtansine (T-DM1) are the ADCs under investigation. The rate of SBN until the last follow-up date or until December 2023 and the cumulative incidence of SBN with death as a competing event were compared between the two groups with and without concurrent ADC. Univariable and multivariable models were developed using Fine and Gray competing risks regression, and subdistribution hazard ratios (SHRs) are shown with 95% confidence interval (CI).
Results: Among the 168 patients who met the criteria, 48 (29%) received ADC, and 19 (11%) received concurrent ADC: T-DXd (n = 4) or T-DM1 (n = 15). Key characteristics were the median age of 57 and the HER2-positive status of 36%. Radiotherapy underwent SRS in 60%, and 33% had a prior radiation history. Maximum tumor volume larger than 14 mL were in 24% of patients, and neurologic symptoms were present in 62%. In a median follow-up time of 31 months and median survival time of 15 months, eighteen SBN events (11%) were registered overall. The distribution of these SBNs was 11 patients in grade 2 requiring steroids, 7 patients in grade 3, 6 of whom underwent surgery, and 1 was treated with bevacizumab. Between the groups, 5 cases (26%) out of 19 concurrent ADC patients, in contrast to 13 cases (9%) of the other 149 patients. The two-year cumulative incidence of SBN was 27% in the concurrent ADC group and 7% in the others (P = 0.014). Concurrent ADC was independently associated with a higher risk of SRN on multivariable analysis (SHR, 3.2 [95% CI: 1.1–9.8], P = 0.039).
Conclusion: The results of this multicenter study suggest that concurrent ADC and radiotherapy are associated with a higher risk of SBN.