Targeted therapy-induced radiation recall

IntroductionRadiation recall (RR) is an acute inflammatory reaction confined to previously irradiated areas after the administration of various pharmacological agents. A diverse range of chemotherapies has been associated with RR but no case series with targeted therapies (TT) has been reported.Patients and methodsFrom a database of 346,933 cancer patients ⩾18 years treated at Institut Gustave Roussy between June 1986 and August 2012, clinical data and the pattern of treatment of TT-induced RR were collected. Results were compared with those of prior TT-induced RR publications.ResultsSixteen patients with different tumour types were diagnosed with RR observed in the heart, bladder, salivary glands, skin and gastrointestinal tract. The median duration of RR was 1.7 weeks (range: 0.1–13.7) and median time to onset from TT to RR was 16.9 weeks (range: 1–86.9). TT consisted of inhibitors of the mammalian target of rapamycin (mTOR) (n = 5), endothelial growth factor receptor (EGFR) (n = 2), integrin (n = 2), histone deacetylase (HDAC) (n = 2), cell division cycle 7 (CDC7) (n = 1), insulin-like growth factor 1 receptor (IGFR1) (n = 1), cyclin-dependent kinase (CDK) (n = 1), BRAF (n = 1) and a vascular disrupting agent (VDA) (n = 1). Thirteen incriminated TT (81%) were evaluated during early clinical trials and RR led to discontinuation of TT in six patients. All patients had previously received radiotherapy at a median biologically effective dose (BED) of 47 Gy (range: 20–70). The median interval from radiation to TT was 30 months (range: 0.3–363). Immunohistochemical analysis of skin biopsy specimens did not show any transforming growth factor-beta (TGF-β) activation. TT-induced RR characteristics in our population were comparable to those of the nine other cases previously reported in the literature.ConclusionThis is the largest case series ever reported on TT-induced RR. RR could be a potential dose-limiting toxicity in early clinical trials. Research is warranted to further understand the exact pathophysiology of this rare but clinically relevant phenomenon.