Abstract
Background: It is recognized that various radiation-induced malignancies often follow childhood radiotherapy. Radiation-induced neoplasms have been shown to occur with increased frequency in syndromes due to mutated tumor suppressor genes. There exist no recommendations for the management of cancer patients with germline APC gene mutations. Preclinical data suggest that APC gene mutations cause enhanced radiosensitivity, but no clinical observations exist that show that patients with this mutation are at higher risk for radiation-induced malignancies. Results: We report the case of a 32-year-old man with a genetic diagnosis of familial adenomatous polyposis (FAP) who initially presented at age 10 with a medulloblastoma treated with radiotherapy and surgery. Radiation-induced papillary thyroid carcinoma followed 13 years later. Finally, radiation-induced soft tissue osteosarcoma occurred with widespread metastasis 20 years thereafter. Conclusions: This is the first report of 2 malignancies in the prior radiotherapy fields of a patient with a genetic diagnosis of FAP. More important, this suggests that APC-defective cells are at an enhanced sensitivity to the carcinogenic effects of radiotherapy compared with APC-proficient cells. This could argue for genetic screening in affected members of these families and for creation of treatment recommendations to more seriously consider the risks of radiation therapy.
Highlights
While medulloblastoma and radiation-induced thyroid carcinoma have been reported in patients with familial adenomatous polyposis (FAP), radiation-induced soft tissue osteosarcoma has not been reported.[4]
A 32-year-old African American male with a clinical family history of FAP in his mother and 1 of 2 siblings was diagnosed with medulloblastoma at age 10
The use of radiation therapy (RT) for neoplasms in patients with a clinical or molecular FAP diagnosis should prompt vigilant long-term follow-up due to the risk of secondary neoplasms arising in the radiation fields
Summary
Several studies have implicated radiation therapy (RT) in the pathogenesis of secondary malignant neoplasms after treatment for a primary cancer; approximately two thirds of these secondary malignant neoplasms occur in or at the edge of the irradiated field.[1,2,3] While medulloblastoma and radiation-induced thyroid carcinoma have been reported in patients with familial adenomatous polyposis (FAP), radiation-induced soft tissue osteosarcoma has not been reported.[4]. Preclinical data suggest that APC gene mutations result in enhanced radiosensitivity, but no clinical observations exist that show that patients with this mutation are at higher risk for radiation-induced malignancies.[5,6,7]. Conclusions: This is the first report of 2 malignancies in the prior radiotherapy fields of a patient with a genetic diagnosis of FAP More important, this suggests that APC-defective cells are at an enhanced sensitivity to the carcinogenic effects of radiotherapy compared with APC-proficient cells. This suggests that APC-defective cells are at an enhanced sensitivity to the carcinogenic effects of radiotherapy compared with APC-proficient cells This could argue for genetic screening in affected members of these families and for creation of treatment recommendations to more seriously consider the risks of radiation therapy
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