Subsequent neoplasms in survivors of childhood central nervous system tumors: risk after modern multimodal therapy

Historically, primary surgical resection was responsible for early improvements in the overall survival of children diagnosed with CNS tumors. Further improvements in survival have been achieved in more recent decades, with the addition of CNS-directed radiotherapy (RT) and/or systemic chemotherapy.1–3 For example, marked increases in overall survival of children with medulloblastoma were achieved by the addition of craniospinal RT and systemic chemotherapy after primary tumor resection.1,4–7 However, with these improvements in overall survival, it also became clear that survivors of CNS tumors are at increased risk for therapy-related long-term morbidities and mortality.5–8 One of the most serious late effects is the development of subsequent neoplasms (SNs), where risk continues to increase decades following primary cancer therapy.5,9,10 While RT and specific chemotherapeutic agents have both been independently associated with an increased risk for SNs, it is unclear what the magnitude of risk may be among CNS survivors exposed to multimodal therapy. Early studies have suggested that the risk may be high, with reported rates of ∼4% at 10 years.11–15 However, in addition to limited length of follow-up, these studies have lacked direct comparison to populations treated prior to the use of multimodal therapy for medulloblastoma. Therefore, this study aims to estimate the overall cumulative incidence of SNs in the large population of CNS tumor survivors treated at St Jude Children's Research Hospital (SJCRH) and to explore whether the introduction of multimodal therapy for medulloblastoma has resulted in an increased incidence of SNs.