GammaKnife radiosurgery appears to be safe regardless of whether it is delivered before or after checkpoint inhibitor immunotherapy. Conversely, WBRT delivered after immunotherapy was associated with heightened rates of grade ≥ 3 toxicity, including life-threatening cerebral edema, in approximately one-quarter of courses in this sample.
Charles E. Rutter, MD, Trevor Bledsoe, MD, Mark Bi, Roy H. Decker, MD, PhD; Yale University School of Medicine
BACKGROUND: Immunotherapy is increasingly used for patients with advanced malignancies, many of whom will also require treatment for brain metastases at some point during their illness. However, the safety of brain radiation after immunotherapy is unknown. We therefore sought to compare the toxicity profiles of GammaKnife radiosurgery (GKRS) vs whole-brain radiation therapy (WBRT) among patients treated with immunotherapy.
METHODS: Patients treated with checkpoint inhibitor immunotherapy at our institution who also received GKRS or WBRT before or after the initiation of immunotherapy were identified. Toxicity data were obtained and classified according to Common Terminology Criteria for Adverse Events version 5.0. Fisher’s exact test was used to compare occurrence of acute grade ≥ 3 toxicity between courses of GKRS vs WBRT, as well as within the GKRS and WBRT groups, based upon relative timing of radiation and the initiation of immunotherapy.
RESULTS: A total of 94 courses were identified, consisting of 71 courses of GKRS (33 before and 38 after immunotherapy) and 23 courses of WBRT (8 before and 15 after immunotherapy). Grade ≥ 3 toxicity occurred in three (9.4%) GKRS courses before and four (10.8%) courses after immunotherapy (P = .58). WBRT after immunotherapy was associated with a nonstatistically significant increase in grade ≥ 3 toxicity (42.9% vs 12.5%, respectively; P = .19). Rates of grade ≥ 3 toxicity of either GKRS or WBRT before immunotherapy did not differ (9.4% vs 12.5%; P = .99). Grade ≥ 3 toxicity was significantly higher with WBRT vs GKRS when delivered after immunotherapy (42.9% vs 10.8%; P = .02). Acute grade 4 cerebral edema occurred in four WBRT courses following immunotherapy (26.7%).
CONCLUSIONS: GKRS appears to be safe regardless of whether it is delivered before or after checkpoint inhibitor immunotherapy. Conversely, WBRT delivered after immunotherapy was associated with heightened rates of grade ≥ 3 toxicity, including life-threatening cerebral edema, in approximately one-quarter of courses in this sample. These results provide an early assessment of the safety of integrating immunotherapy and brain radiation, and require further validation.
Proceedings of the 98th Annual Meeting of the American Radium Society -americanradiumsociety.org