The prognosis of childhood cancers has improved markedly, and the proportion of long-term survivors has increased in recent years. However, with the increase in the number of long-term survivors, the development of latent treatment-related adverse effects, such as secondary malignancies, has generated new problems. Secondary cancer is defined as a histologically distinct malignancy that develops at least 2 months after the completion of treatment for primary cancer. Genetic factors and acquired conditions associated with treatment modalities are possible causes of secondary malignancy development. Genetic factors include the presence of Li-Fraumeni syndrome (LFS) and retinoblastoma. In terms of acquired factors, radiation and chemotherapy have been reported to be the most strongly associated with secondary malignancy development. The use of alkylating agents and topoisomerase II inhibitors for the treatment of childhood cancer increases the subsequent risk of secondary tumors. We herein investigated three cases of secondary osteosarcoma several years after treatment for primary cancer. In the three patients, the familial history did not appear to fit the clinical diagnostic criteria of LFS or retinoblastoma. The patients had not received previous radiation therapy to the anatomical site of the secondary cancer. However, high dosages of alkylating agents and topoisomerase II inhibitors had been administered for the treatment of primary cancer. The exact link between chemotherapy and secondary cancer remains elusive, but the possibility of an association should be considered. Following the development of multidisciplinary therapies, long-term follow-up and monitoring of latent adverse effects may be necessary for childhood cancer survivors.
Keywords: chemotherapy; childhood cancer; latent adverse effect; osteosarcoma; secondary cancer.