Second Malignancies Following Treatment for Childhood Cancer

Abstract

Second or subsequent malignant neoplasms (SMNs) are defined as histologically distinct cancers developing after the occurrence of a first cancer and are one of the most devastating consequences of cancer therapy in children with cancer. Studies following large cohorts of childhood cancer survivors have reported a three- to sixfold increased risk of SMNs compared with the background incidence of cancer in the general population; this risk continues to increase as the cohort ages. Follow-up of a Nordic cohort of 47,697 patients diagnosed with their first cancer at 19 years of age or younger between 1943 and 2005 resulted in the identification of 1,180 SMNs [1]. The cohort was at a 3.3-fold increased risk of developing an SMN when compared with an age- and gender-matched healthy population. The relative risk (RR) was statistically significantly increased in all age groups, even for cohort members approaching 70 years of age. Another population-based cohort of 17,981 5-year survivors of childhood cancer diagnosed before the age of 15 years in Great Britain between 1940 and 1991 was followed for a median of 24 years; 1,354 SMNs were observed, and the cohort was at a fourfold increased risk of developing a new cancer, when compared with the general population [2]. A retrospective cohort of 14,359 children diagnosed between 1970 and 1986 in the USA before the age of 21 years, and surviving at least 5 years, was followed by the Childhood Cancer Survivor Study (CCSS) [3]. The estimated 30-year cumulative incidence was 7.9 % for SMNs (excluding nonmelanoma skin cancers, Fig. 19.1). Overall, the cohort was at a sixfold increased risk of developing a second cancer. Female sex, older age at diagnosis, earlier treatment era, and treatment with radiation were associated with an increase in risk of SMNs. Childhood cancer survivors are at risk for the development of multiple primaries; the cumulative incidence of a third primary approaches 47 % at 20 years after the second primary [4]. Radiation-exposed survivors, who developed a nonmelanoma skin cancer as an SMN, carry a higher risk of a subsequent invasive SMN when compared with those without a history of a nonmelanoma skin cancer.