Brain radiosurgery and ipilimumab (Ipi) in melanoma brain metastases (MBM) patients: Does an enhanced immune response induce radionecrosis (RN)?

Abstract

e20019 Background: The anti-CTLA4 antibody, ipi, improves survival in metastatic melanoma. Combined radiotherapy (RT) and ipi may increase immune response to improve outcomes but also increase toxicity. This study reports the outcomes, including incidence of radionecrosis (RN), in patients (pt) with MBM treated with ipi and brain radiosurgery (SRS) and whole brain treatment (WBRT). Methods: Pt with MBM treated with WBRT or SRS and ipi at the Princess Margaret from 2008-2014 were reviewed to evaluate clinical characteristics, time between RT and ipi treatment, toxicity, response and survival. Results: We identified 54 pts treated with ipi and RT (SRS and/or WBRT), 34 who were evaluable (20 were excluded due to lack of follow up imaging), (see table). Median follow up was 7.4 months (m); OS 6.4m, PFS 2.7m. No RN was seen with WBRT alone, but RN occurred in 11/27 (41%) pt who received SRS: 7 received RT within 4m of ipi (SRS = 4, SRS+WBRT = 3) and 4 received RT outside of this window (SRS = 2, SRS+WBRT= 2). Larger tumor volume and V12Gy was associated with a higher rate of RN. Symptomatic RN was treated with steroids in 6 pt. Only 1 of 6 pt needed surgical excision, which showed necrosis, inflammatory T cells, macrophages, and treated melanoma. Intracranial MBM progression during ipi occurred in 7 pt: 6 discontinued ipi after 1-3 cycles and 1 continued to complete all 4 cycles ipi. Eventual MBM response was seen in the pt who completed ipi and 1 pt who received 3 cycles. Conclusions: When brain RT is combined with ipi, RN occurred in 41% of pts treated with SRS (± WBRT) and ipi but 0% after WBRT and ipi. Symptomatic RN generally responded to steroids. In 1 case requiring surgery, pathology demonstrated an increased immunological effect. MBM progression during ipi did not prohibit later cranial response. Characteristic Number Age Median (range) 53 (24-82) Sex Male 22 Female 12 Ipilimumab infusions Median (range) 4 (1-4) Radiotherapy treatment SRS 12 SRS + WBRT 15 WBRT 7 Median SRS dose (range) 21(15-24) Median no. fractions 2(1-4) LDH Median (range) 242 (155-1148)