Childhood cancer survivors are vulnerable to treatment-related late effects, which include physical and psychosocial morbidity, subsequent malignancies, and premature death.  Symptoms representing one's perceptive abnormal physical, emotional, or psychosomatic state are common late effects in childhood cancer survivors.  Survivors often experience multiple, concurrent symptoms, known as a symptom cluster.  Although the association between symptom presence and poor quality of life in childhood cancer survivors has been reported, it is uncertain whether individual symptom domains and clusters change over time, and whether the change in individual symptom domains and clusters are associated with adverse health outcomes, including chronic conditions and premature mortality.  In addition, very few studies have examined if specific cancer therapeutic exposures (e.g., cranial irradiation, anthracyclines, and alkylating agents) contribute to the change in individual symptoms and symptom clusters over time.  Our long-term goal of cancer survivorship care is to identify important symptoms for early indication of adverse health events (e.g., cardiac arrest and premature mortality), and to design interventions targeting at symptoms for promotion of healthy aging in cancer survivors.  To achieve this goal, the current study proposes two specific aims: 1) to investigate the presence of individual symptom domains (sensation abnormality, motor/movement problems, cardiac symptoms, pulmonary symptom, pain, anxiety, depression, and somatization) and symptom clusters across multiple time points spanning 25 years in adult survivors of childhood cancers, and investigate the transition of symptom clusters over time, and 2) to investigate the prognostic value of individual symptom domains and symptom clusters for the development of chronic conditions and premature mortality in adult survivors of childhood cancers.  The proposed study will overcome the limitations of previous research by utilizing repeated symptom data collected from participants in the Childhood Cancer Survivor Study to elucidate the extent to which symptom progress is associated with mortality and with chronic conditions identified during risk-based comprehensive medical assessment in the St. Jude Lifetime Cohort Study (N>700) at St. Jude Children's Research Hospital.  We will group chronic conditions by eight organ systems: cardiovascular, endocrine/reproductive, hepatic, neurocognitive, neurosensory, skeletal, pulmonary, and urinary categories.  In addition, we will develop a classification methodology to identify symptom clusters based on eight individual symptom domains, and use a transition analytic method to capture the change in symptom cluster over time.  Our team includes renowned researchers with expertise in patient-reported outcomes, symptom measurement, psychology, pediatric/adult survivorship care, and translational science research.