Treatment
Patients treated with nivolumab received intravenous infusions at a dose of 3 mg/kg once every two weeks. A cycle of therapy was operationally defined as 28 days, during which nivolumab was administered on day 1 and day 14. Patients treated with pembrolizumab received intravenous infusions at a dose of 2 mg/kg once every three weeks. A cycle of therapy was operationally defined as 21 days, during which pembrolizumab was administered on day 1 and day 21. Treatment was repeated every 14 days for nivolumab, and every 21 days for pembrolizumab, provided all hematologic toxicity from the previous cycle had resolved to grade 2 or less, and all non-hematologic toxicities recovered to either grade 1 or less. When indicated, the subsequent ICI cycle was delayed until these criteria were met.
Radiotherapy planning volumes were contoured by a radiation oncologist and a neurosurgeon. Dose and fractionation were determined on the basis of lesion size, prior radiotherapy, and meeting dose constraints for adjacent organs at risk. For treatment planning, high-resolution thin-slice magnetic resonance T1 sequences with contrast were rigidly fused to CT simulation scans. All patients were treated using non-coplanar volumetric modulated arc therapy (VMAT) using 3-4 arcs and either 6X or 10X flattening filter-free beams that maintained a minimum coverage of 95% of the planning target volume receiving 100% of the prescription dose. The treatment plans were generated using Eclipse v15.6 (Varian Medical Systems, Palo Alto, CA) with either AAA or AcurosXB calculation algorithms. All dose constraints for SBRT plans were evaluated using TG101 guidelines. Patients were treated on a Novalis (BrainLab, Munich, Germany) Truebeam STX linac (Varian Medical Systems, Palo Alto, CA), with multileaf collimator leaf width of 2.5 mm.