Targeted therapy-induced radiation recall

Introduction: Radiation 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 methods: From 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. Results: Sixteen 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. Conclusion: This 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.