Distant brain failure after stereotactic radiosurgery for brain metastases in patients receiving novel systemic treatments

Novel systemic therapies, such as immunotherapy and targeted therapies, have shown better systemic disease control in the last decennium. However, the effect of these treatments on distant brain failure (DBF) in patients with brain metastases (BM) remains a topic of discussion. Improving time to DBF leads to longer overall survival (OS), as is reflected in the brain metastasis velocity (BMV). This study presents real world data about the combined effects of local and systemic treatments on DBF and survival. A retrospective consecutive cohort study was conducted. Patients with newly diagnosed BM were included between June 2018 and May 2020. Factors associated with DBF were analyzed in multivariate models. The association between BMV and overall survival was analyzed with linear regression analysis. Three hundred and three patients were included. Two hundred and sixty-two (86%) patients received stereotactic radiotherapy, 41 (14%) awaited in first instance the intracranial effect of newly started or switched systemic treatment. Median time to DBF after radiotherapy was 21 months (95% CI 15-27), median OS was 20 months (IQR 10-36). Receiving immunotherapy or targeted therapy were associated with a lower hazard of DBF, compared with chemotherapy. The presence of > 5 initial BM and progressive or stable extracranial disease were associated with increased DBF. BMV was significantly associated with overall survival. In this retrospective cohort, patients who received immunotherapy or targeted therapy experienced a reduced risk of DBF in comparison to those treated with chemotherapy. A higher BMV was associated with a decreased OS.