Second Malignant Neoplasms

Abstract

Second malignant neoplasms (SMNs) are a well-recognized complication among childhood cancer survivors. Childhood cancer survivors are at a three- to six-fold increased risk of developing SMNs compared with the background incidence of cancer in the general population. SMNs are classified into two distinct groups, based primarily on the unique associations with specific therapeutic exposures: chemotherapy-related myelodysplasia and acute myeloid leukemia (t-MDS/AML), and radiation-related solid SMNs. Characteristics of t-MDS/AML include a latency ~3 years from primary cancer diagnosis and association with alkylating agents (e.g. cyclophosphamide, ifosfamide, mechlorethamine, melphalan, chlorambucil, nitrosoureas, busulfan, platinum compounds and procarbazine) and/or topoisomerase II inhibitors (e.g. etoposide). Solid SMNs have a well-defined association with radiation, and are characterized by a latency that typically exceeds 10 years. Eighty percent of the entire burden of SMNs is accounted for by radiation-related solid SMNs, such as breast, skin and thyroid cancer, central nervous system (CNS) tumors, and bone and soft tissue sarcomas. Considerable inter-individual variability is observed in the risk of developing SMNs for a given therapeutic exposure. Genetic predisposition and especially its interaction with therapeutic exposures can potentially exacerbate the toxic effect of treatment on normal tissues and organ systems, and can possibly explain the inter-individual variability. Understanding the etio-pathogenetic pathways that lead to the development of SMNs is critical to developing targeted prevention and intervention strategies (screening for early detection), optimizing risk-based health care of cancer survivors, thus minimizing SMNs and improving quality of life.