In the general population, psychological symptoms frequently co-occur; however, profiles of symptom comorbidities have not been examined among adolescent survivors of childhood cancer. Patients and MethodsParents of 3,893 5-year survivors of childhood cancer who were treated between 1970 and 1999 and who were assessed in adolescence (age 12 to 17 years) completed the Behavior Problems Index. Age-and sex-standardized z scores were calculated for symptom domains by using the Childhood Cancer Survivor Study sibling cohort. Latent profile analysis identified profiles of comorbid symptoms, and multivariable multinomial logistic regression modeling examined associations between cancer treatment exposures and physical late effects and identified symptom profiles. Odds ratios (ORs) and 95% CIs for latent class membership were estimated and analyses were stratified by cranial radiation therapy (CRT; CRT or no CRT). ResultsFour symptoms profiles were identified: no significant symptoms (CRT, 63%; no CRT, 70%); elevated anxiety and/or depression, social withdrawal, and attention problems (internalizing; CRT, 31%; no CRT, 16%); elevated headstrong behavior and attention problems (externalizing; CRT, no observed; no CRT, 9%); and elevated internalizing and externalizing symptoms (global symptoms; CRT, 6%; no CRT, 5%). Treatment with $ 30 Gy CRT conferred greater risk of internalizing (OR, 1.7; 95% CI, 1.0 to 2.8) and global symptoms (OR, 3.2; 95% CI, 1.2 to 8.4). Among the no CRT group, corticosteroid treatment was associated with externalizing symptoms (OR, 1.9; 95% CI, 1.2 to 2.8) and $ 4.3 g/m 2 intravenous methotrexate exposure was associated with global symptoms (OR, 1.5; 95% CI, 0.9 to 2.4). Treatment late effects, including obesity, cancer-related pain, and sensory impairments, were significantly associated with increased risk of comorbid symptoms. ConclusionBehavioral, emotional, and social symptoms frequently co-occur in adolescent survivors of childhood cancer and are associated with treatment exposures and physical late effects. Assessment and consideration of symptom profiles are essential for directing appropriate mental health treatment for adolescent survivors.

Author contributions:Vuotto: conception and design; analysis and interpretation of data; drafting the article and revising it critically for important intellectual content; final approval of the version to be published Krull: conception and design; analysis and interpretation of data; drafting the article and revising it critically for important intellectual content; final approval of the version to be published Li: analysis and interpretation of data; revising the article for critically for important intellectual content; final approval of the version to be published Oeffinger: conception and design; acquisition of data; drafting the article and revising it critically for important intellectual content; final approval of the version to be published Green: conception and design; acquisition of data; revising the article for critically for important intellectual content; final approval of the version to be published Patel: conception and design; revising the article for critically for important intellectual content; final approval of the version to be published Srivastava: analysis and interpretation of data; revising the article for critically for important intellectual content; final approval of the version to be published Stovall: conception and design; acquisition of data; revising the article for critically for important intellectual content; final approval of the version to be published Ness: conception and design; revising the article for critically for important intellectual content; final approval of the version to be published Armstrong: conception and design; revising the article for critically for important intellectual content; final approval of the version to be published; funding acquisition Robison: conception and design; acquisition of data; revising the article for critically for important intellectual content; final approval of the version to be published; funding acquisition Brinkman: conception and design; analysis and interpretation of data; drafting the article and revising it critically for important intellectual content; final approval of the version to be published Dr. Brinkman is responsible for the overall content of the article. Conclusions-Chronic health conditions resulting from childhood cancer therapies contribute to emotional distress in adult survivors. Targeted mental health screening efforts in this at-risk population appear warranted. Therapeutic approaches should consider the complex interplay between chronic health conditions and symptoms of emotional distress. HHS Public Access Graphical AbstractPrecis: Survivors who have been exposed to cancer directed therapies in childhood are at increased risk for developing cardiac, endocrine and pulmonary chronic health conditions. These chronic health conditions contribute to emotional distress symptoms in adult survivors of childhood cancer.

Drinking initiation during adolescence is associated with modest increased risk for memory impairment and emotional distress in adult survivors of childhood cancer.

Objective: To examine the potential mediating role of body image dissatisfaction on the association between treatment-related scarring/disfigurement and psychological distress in adult survivors of childhood cancer. groups (cancer-related and general) based on factor analysis. Using causal mediation analysis, we estimated the proportion of psychological distress associated with treatment-related scarring/disfigurement that could be eliminated by resolving BID through a hypothetical intervention. Methods:Results: Among survivors with scarring/disfigurement of the head, a sizable proportion of the relative excess of psychological distress could be eliminated if BID was successfully treated | VariablesOur outcomes of interest included depression, anxiety, and posttraumatic stress. Depression and anxiety were assessed using the Brief Symptom Inventory-18 (BSI-18), an 18-item self-report measure of acute psychological distress symptoms. 17 By using sex-specific normative data, impairment was defined as scores falling ≥90th percentile (Tscore of 63 or greater) for each subscale. Posttraumatic stress symptoms (PTSSs) were assessed using the Posttraumatic Stress DisorderChecklist, 18 a 17-item measure of diagnostic symptom criteria listed in the Diagnostic and Statistical Manual for Psychiatric Disorders, 4thEdition (DSM-IV-TR). 19 Posttraumatic stress symptom was defined by the report of at least 1 re-experiencing symptom, at least 3 avoidance symptoms, and at least 2 arousal symptoms, each with a minimum response of 3 ("moderate").Our exposure of interest, scarring/disfigurement, was assessed and/or ≥ grade 1 growth hormone abnormality. Body mass index was abstracted from medical records and was adjusted for amputation. | Statistical methods