Letters to the Editor

RADIATION RECALL AND RADIOSENSITISATION WITH ALKYLATING AGENTS

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.

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.

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.

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.

Radiation recall is an inflammatory skin reaction at a previously irradiated field subsequent to the administration of a variety of pharmacologic agents. Although skin has been the major site of radiation recall toxicity, instances involving other organ have been reported.

Data for this review were identified by searches of Medline and Cancerlit. The search terms “radiation”, “recall”, and “toxicity” were used. References identified from within retrieved articles were also used. There was no limitation on year of publication and no abstract forms were included. Only articles published in English were taken into consideration.

Idiosyncratic drug hypersensitivity phenomenon is a recent hypothesis which correlates best with the available facts at this moment. The phenomenon may occur days to years after radiotherapy has been completed. The majority of the drugs commonly used in cancer therapy have been involved in the radiation recall phenomenon. A mixed non-specific inflammatory infiltrate seems to be the common histopathologic criteria in previous published reports. Universally, corticosteroids or the use of non-steroidal anti-inflammatory agents, in conjunction with withdrawal of the offending agent, produce prompt improvement.

We propose to collect all future radiation recall phenomenon in a Rare Cancer Network database in order to augment our understanding of this rare reaction.

Radiation recall dermatitis secondary to gemcitabine use has been reported in isolated cases of patients treated for breast and lung cancers. There have been no reports of radiation recall dermatitis from gemcitabine after whole pelvic radiation therapy employed as a treatment of a gynecologic cancer.

A 67-year-old woman was treated with whole pelvic radiation for palliation of lower extremity swelling and pain due to recurrent ovarian adenocarcinoma. Three months later, the patient was treated with gemcitabine for three courses. Therapy was discontinued secondary to severe cellulitis and edema of the skin of the anterior abdominal wall in the field of her prior radiation therapy.

Radiation recall dermatitis secondary to gemcitabine should be considered in any patient with pelvic or lower abdominal skin abnormalities after pelvic radiation and subsequent gemcitabine therapy.