Toxicity of concurrent stereotactic radiotherapy and targeted therapy or immunotherapy: A systematic review

Background and purpose: Both stereotactic radiotherapy (SRT) and immune- or targeted therapy play an increasingly important role in personalized treatment of metastatic disease. Concurrent application of both therapies is rapidly expanding in daily clinical practice. In this systematic review we summarize severe toxicity observed after concurrent treatment. Material and methods: PubMed and EMBASE databases were searched for English literature published up to April 2016 using keywords radiosurgery, local ablative therapy, gamma knife and stereotactic, combined with bevacizumab, cetuximab, crizotinib, erlotinib, gefitinib, ipilimumab, lapatinib, sorafenib, sunitinib, trastuzumab, vemurafenib, PLX4032, panitumumab, nivolumab, pembrolizumab, alectinib, ceritinib, dabrafenib, trametinib, BRAF, TKI, MEK, PD1, EGFR, CTLA-4 or ALK. Studies performing SRT during or within 30 days of targeted/immunotherapy, reporting severe (>= Grade 3) toxicity were included. Results: Concurrent treatment is mostly well tolerated in cranial SRT, but high rates of severe toxicity were observed for the combination with BRAF-inhibitors. The relatively scarce literature on extra cranial SRT shows a potential risk of increased toxicity when SRT is combined with EGFR-targeting tyrosine kinase inhibitors and bevacizumab, which was not observed for cranial SRT. Conclusions: This review gives a best -possible overview of current knowledge and its limitations and underlines the need for a timely generation of stronger evidence in this rapidly expanding field. (C) 2016 The Author(s). Published by Elsevier Ltd.