Secondary Malignancy


The cure for children cancer has improved during the past decades with five-year survival rates approaching 80%. As the numbers in survival improves there is increased awareness of the risk of developing a secondary malignancy due to therapy. Subsequent malignant neoplasms are the most common non-relapse cause of late mortality  accounting for almost half of all non-relapse deaths among five-year survivors. Radiotherapy has been strongly associated with development of secondary malignancy, and dose-response relationship has also been identified for specific chemotherapeutic agents including alkylating and epipodophyllotoxins agents. Hodgkin lymphoma survivors are at particular high-risk for subsequent secondary malignancies with an almost one-third cases in this group of survivors. Secondary malignancy of the breast and gastrointestinal tract most commonly follows a primary diagnosis of Hodgkin lymphoma (HL). Female breast cancer accounts for almost 20% of subsequent malignant neoplasms of most cohort groups studied. Second thyroid cancers are most common in leukemia and HL survivors as were skin melanomas. The thyroid gland is highly susceptible to the carcinogenic effects of ionizing radiation. Secondary sarcomas with 15% incidence predominantly occur among survivors of primary soft tissue sarcoma or HL and the risk is associated to exposure to anthracyclines, alkylating agents and radiation therapy. Secondary hematopoietic cancers most commonly follow a primary diagnosis of HL or leukemia. Second malignancy of the central nervous system (CNS) with an almost 10% incidence most commonly occurs after an original diagnosis of a CNS tumor or leukemia. There is a linear relation between radiation doses received during treatment for childhood cancer and the relative risk of subsequent gliomas or meningiomas. Non-melanoma skin cancer (basal cell and squamous cell) is another secondary malignancy rarely fatal occurring with an increase incidence in survivors of HL, leukemia and CNS tumors related to radiation therapy exposure. Females are at increased risk for breast, thyroid, non-melanoma skin and meningiomas. The period of higher risk for secondary malignancy occurs before age of 40 years.    

1- Meadows AT, Friedman DL, Neglia JP, et al: Second neoplasms in survivors of childhood cancer: findings from the Childhood Cancer Survivor Study cohort. J Clin Oncol. 27(14):2356-62, 2009
2- Friedman DL, Whitton J, Leisenring W, et al: Subsequent neoplasms in 5-year survivors of childhood cancer: the Childhood Cancer Survivor Study. J Natl Cancer Inst. 102(14):1083-95, 2010
3- Turcotte LM, Whitton JA Friedman DL, et al: Risk of Subsequent Neoplasms During the Fifth and Sixth Decades of Life in the Childhood Cancer Survivor Study Cohort.  J Clin Oncol. 33(31):3568-75, 2015
4- MacArthur AC, Spinelli JJ, Rogers PC, Goddard KJ, Phillips N, McBride ML: Risk of a second malignant neoplasm among 5-year survivors of cancer in childhood and adolescence in British Columbia, Canada. Pediatr Blood Cancer. 48(4):453-9, 2007
5- Reulen RC, Frobisher C, Winter DL, et al; British Childhood Cancer Survivor Study Steering Group: Long-term risks of subsequent primary neoplasms among survivors of childhood cancer. JAMA. 305(22):2311-9, 2011
6- Turcotte LM, Liu Q, Yasui Y, et al: Temporal Trends in Treatment and Subsequent Neoplasm Risk Among 5-Year Survivors  of Childhood Cancer, 1970-2015. JAMA. 317(8):814-824, 2017
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