Stephanie G C Kroeze1, Corinna Fritz2, Morten Hoyer3, Simon S Lo4, Umberto Ricardi5, Arjun Sahgal6, Rolf Stahel7, Roger Stupp7, Matthias Guckenberger2. 1. Department of Radiation Oncology, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland. Electronic address: Stephanie.kroeze@usz.ch. 2. Department of Radiation Oncology, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland. 3. Danish Center for Particle Therapy, Aarhus University, Palle Juul-Jensens Boulevard, 8200 Aarhus, Denmark. 4. Department of Radiation Oncology, University of Washington School of Medicine, 1959 N.E. Pacific Street, Box 356043, Seattle, USA. 5. Department of Oncology, University of Turin, Regione Gonzole 10, 10043 Orbassano, Italy. 6. Department of Radiation Oncology, University of Toronto, 27 King's College Circle Toronto, Ontario M5S 1A1, Canada. 7. Department of Oncology, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland.
Abstract
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 30days 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.
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 30days 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.
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