PERSONALIZED RISK PREDICTION FOR CANCER SURVIVORS: A GENERALIZED BAYESIAN SEMI-PARAMETRIC MODEL OF RECURRENT EVENTS WITH COMPETING OUTCOMES.

Multiple primary cancers are increasingly more frequent due to improved survival of cancer patients. Characteristics of the first primary cancer largely impact the risk of developing subsequent primary cancers. Hence, model-based risk characterization of cancer survivors that captures patient-specific variables is needed for healthcare policy making. We propose a Bayesian semi-parametric framework, where the occurrence processes of the competing cancer types follow independent non-homogeneous Poisson processes and adjust for covariates including the type and age at diagnosis of the first primary. Applying this framework to a historically collected cohort with families presenting a highly enriched history of multiple primary tumors and diverse cancer types, we have derived a suite of age-to-onset penetrance curves for cancer survivors. This includes penetrance estimates for second primary lung cancer, potentially impactful to ongoing cancer screening decisions. Using Receiver Operating Characteristic (ROC) curves, we have validated the good predictive performance of our models in predicting second primary lung cancer, sarcoma, breast cancer, and all other cancers combined, with areas under the curves (AUCs) at 0.89, 0.91, 0.76 and 0.68, respectively. In conclusion, our framework provides covariate-adjusted quantitative risk assessment for cancer survivors, hence moving a step closer to personalized health management for this unique population.