Synergy.

It goes both ways, with efficacy on one side and toxicity on the other. Radiosurgery (SRS) is increasingly becoming the standard for both intact and resected brain mets. So how do we reconcile this with the growing number of patients on targeted agents: Should we pause systemic therapy based on half-life, intentionally prescribe concurrent modalities, or not even care? Last week’s retrospective review of the Dana Farber experience offers some insight into the safety of performing SRS with immunotherapy. Among 480 patients undergoing SRS, those who at some point (timing unclear) received immunotherapy--specifically PD-1 and CTLA-4 inhibitors--had 2.5 times the risk of radionecrosis. This risk was highest (HR 4.7) for patients with metastatic melanoma on ipilimumab. This data suggests a need to explore whether immunotherapy breaks prior to SRS could help prevent radionecrosis, a scenario that often necessitates steroids that then curb the efficacy of immunotherapy. It looks like the synergy we hoped to find with SRS and immunotherapy has taken a turn towards toxicity.