title: Early and Severe Radiation Toxicity Associated with Concurrent Sirolimus in an Organ Transplant Recipient with Head and Neck Cutaneous Squamous Cell Carcinoma: A Case Report.
abstract: We present a case of a 71-year-old man with a history of liver transplantation who was treated with adjuvant radiotherapy with concurrent cisplatin for recurrent cutaneous squamous cell carcinoma of the head and neck. The patient was transitioned from tacrolimus to sirolimus for immunosuppression immediately prior to the start of radiation therapy, with the goal of reducing the risk for further skin cancer recurrence. The patient developed severe normal tissue toxicity, disproportionate to the dose delivered. He was diagnosed with Grade 4 esophagitis and mucositis after just 2,400 cGy in 12 fractions (planned 6,400 cGy in 32 fractions), requiring cessation of therapy. Six months later, the patient was diagnosed with local recurrence and distant metastases in the lung, and unfortunately passed away one month later. Randomized data have demonstrated the anti-neoplastic benefit of sirolimus. Pre-clinical studies and animal models have suggested that sirolimus may be a radiation sensitizer; however, the literature is limited regarding the clinical translation of these biologic findings. The case we presented reflects that concurrent radiation therapy with sirolimus may enhance the cytotoxic effects of radiation therapy and contribute to dose-limiting toxicity. Certainly, further study is necessary to explore this observation.
authors.affiliation: Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH, U.S.A.
authors.forename: Bindu V
authors.initials: BV
authors.lastname: Manyam
authors.affiliation: Department of Solid Tumor Oncology, Cleveland Clinic, Cleveland, OH, U.S.A.
authors.forename: Tobenna I
authors.initials: TI
authors.lastname: Nwizu
authors.affiliation: Department of Solid Tumor Oncology, Cleveland Clinic, Cleveland, OH, U.S.A.
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Rahe
authors.affiliation: Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH, U.S.A.
authors.forename: Bridgett A
authors.initials: BA
authors.lastname: Harr
authors.affiliation: Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH, U.S.A. koyfmas@ccf.org.
authors.forename: Shlomo A
authors.initials: SA
authors.lastname: Koyfman
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects; D006258:Head and Neck Neoplasms / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D011832:Radiation Injuries / Q000209:etiology*; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects*; D020123:Sirolimus / Q000009:adverse effects*; D012878:Skin Neoplasms / Q000209:etiology / Q000473:pathology / Q000628:therapy*
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus
keywords: Radiation toxicity; cutaneous squamous cell carcinoma of the head and neck; organ transplant recipient; sirolimus