Combined Clinical And Genetic Risk Prediction Of Central Nervous System Subsequent Neoplasms (Cns Sns) In Childhood Cancer Survivors (Ccs): A Report From The Cog Alteo3n1 Study.

10511Background: CCS are at a 10-fold increased risk of CNS SNs. Cranial radiation (CRT) for primary cancer increases the risk; dose-risk relation with CRT is linear. The substantial burden of CNS SN-related morbidity presents an unmet need for identifying high-risk patients to guide targeted interventions. We present a risk prediction model to address this gap. Methods: CCS with CNS SNs (cases: n=82) matched to CCS without CNS SNs (controls: n=228; matched on primary cancer diagnosis (dx), year of dx, race/ethnicity and follow-up), contributed germline DNA for genotyping 43 previously published candidate genes (97 SNPs). Risk prediction models were derived sequentially: Base Model (age at primary cancer dx, gender), Clinical Model (Base Model + CRT [Y/No]), Final Model (Clinical Model + SNPs). Receiver operating characteristic analysis was used to evaluate predictive utility of Final Model in assessing CNS SN risk. Two risk groups were derived using predicted values (high risk: ≥0.1; low risk: u003c0.1). Res...