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

• Published in: Cancer treatment reviews Vol. 53; pp. 25 - 37
• Main Authors: Kroeze, Stephanie G.C., Fritz, Corinna, Hoyer, Morten, Lo, Simon S., Ricardi, Umberto, Sahgal, Arjun, Stahel, Rolf, Stupp, Roger, Guckenberger, Matthias
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.02.2017
• Subjects: Antineoplastic Combined Chemotherapy Protocols - adverse effects; Bevacizumab - administration & dosage; Bevacizumab - adverse effects; Cetuximab - administration & dosage; Cetuximab - adverse effects; Concurrent; CTLA-4 Antigen - antagonists & inhibitors; Humans; Immunotherapy; Immunotherapy - adverse effects; Molecular Targeted Therapy - adverse effects; Molecular Targeted Therapy - methods; Neoplasms - therapy; Niacinamide - administration & dosage; Niacinamide - adverse effects; Niacinamide - analogs & derivatives; Phenylurea Compounds - administration & dosage; Phenylurea Compounds - adverse effects; Radiosurgery - adverse effects; Stereotactic radiotherapy; Targeted therapy; Toxicity; Targeted therapy; Toxicity; Concurrent; Immunotherapy; Stereotactic radiotherapy
• ISSN: 0305-7372; 1532-1967
• DOI: 10.1016/j.ctrv.2016.11.013

•Cranial SRT is well tolerated when combined with the majority of immuno- or targeted therapies.•Cranial SRT concurrent with BRAF-Inhibitors should be performed with caution due to a risk of cerebral oedema and haemorrhage.•Data on extra-cranial SRT is limited and needs separate evaluation of all drug and target site combinations.•Risk of toxicity is increased after extra-cranial SRT combined with bevacizumab, sorafenib, cetuximab or EGFRi. 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. 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. 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. 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.