Background After childhood acute lymphoblastic leukemia (ALL), sequelae include overweight and obesity, yet with conflicting evidence. We compared the prevalence of overweight and obesity between ≥5‐year ALL survivors from the North American Childhood Cancer Survivor Study (CCSS) and the Swiss Childhood Cancer Survivor Study (SCCSS) and described risk factors. Methods We included adult childhood ALL survivors diagnosed between 1976 and 1999. We matched CCSS participants (3:1) to SCCSS participants by sex and attained age. We calculated body mass index (BMI) from self‐reported height and weight for 1287 CCSS and 429 SCCSS participants; we then compared those with siblings (2034) in North America and Switzerland (678) siblings. We assessed risk factors for overweight (BMI 25–29.9 kg/m2) and obesity (≥30 kg/m2) using multinomial regression. Results We found overweight and obesity significantly more common among survivors in North America when compared with survivors in Switzerland [overweight: 30%, 95% confidence interval (CI): 27–32 vs. 24%, 21–29; obesity: 29%, 27–32 vs. 7%, 5–10] and siblings (overweight: 30%, 27–32 vs. 25%, 22–29; obesity: 24%, 22–26 vs. 6%, 4–8). Survivors in North America [odds ratio (OR) = 1.24, 1.01–1.53] and Switzerland (1.27, 0.74–2.21) were slightly more often obese than siblings. Among survivors, risk factors for obesity included residency in North America (5.8, 3.7–9.0); male (1.7, 1.3–2.3); attained age (≥45 years: 5.1, 2.4–10.8); Non‐Hispanic Black (3.4, 1.6–7.0); low household income (2.3, 1.4–3.5); young age at diagnosis (1.6, 1.1–2.2). Cranial radiotherapy ≥18 Gray was only a risk factor for overweight (1.4, 1.0–1.8); steroids were not associated with overweight or obesity. Interaction tests found no evidence of difference in risk factors between cohorts. Conclusions Although treatment‐related risk for overweight and obesity were similar between regions, higher prevalence among survivors in North America identifies important sociodemographic drivers for informing health policy and targeted intervention trials.

BACKGROUND: The objective of the current study was to characterize and identify factors associated with perceptions of risk of infertility among adult male survivors of childhood cancer. METHODS: A total of 1233 adult male survivors from the Childhood Cancer Survivor Study who were without a history of disease recurrence or subsequent malignancy reported their perceptions of their risk of infertility compared with men never diagnosed with cancer. Survivors were a median age of 37.8 years (range, 22.0-58.7 years) and were 28.4 years from their diagnosis (range, 21.4-39.2 years). Multivariable logistic regression evaluated factors associated with perceptions of risk. RESULTS: Overall, 35.9% of the survivors (443 of 1233 survivors) reported perceptions of their risk of infertility that were discordant with their actual risk based on previous cancer treatment exposures. Discordant perceptions were equally common among men exposed to gonadotoxic therapies (36.3%; 311 of 857 men) and those with no history of gonadotoxic exposure (35.1%; 132 of 376 men). Survivors who fathered children (odds ratio [OR], 4.14; 95% confidence interval [95% CI], 2.74-6.24), had no survivor-focused health care (OR, 3.07; 95% CI, 1.57-5.99), were nonwhite (OR, 2.28; 95% CI, 1.10-4.75), and were of lower income were more likely to report no increased risk of infertility after gonadotoxic treatment. Perceptions of increased risk of infertility among men with no history of gonadotoxic treatment were predicted by never having fathered a child (OR, 1.88; 95% CI, 1.17-3.03), recent participation in survivor-focused health care (OR, 2.11; 95% CI, 1.01-4.42), and higher educational achievement. CONCLUSIONS: Many male survivors of childhood cancer are unaware of how their cancer treatments could impact their reproductive health, underscoring the need for all patients to receive education regarding their risk of infertility throughout the continuum of cancer care. Cancer 2018;124:2447-55. © 2018 American Cancer Society.

Introduction: With survival rates higher than 80%, the number of survivors from pediatric cancer continues to increase. Late effects resulting from cancer and cancer therapy are being characterized, but little information exists on sexual health for men who have survived childhood cancer. Aim: To assess erectile dysfunction (ED) in men who survived childhood and adolescent cancers and to identify potential risk factors for ED. Methods: In total, 1,622 men and 271 eligible brothers in the Childhood Cancer Survivor Study cohort completed the Male Health Questionnaire, which provided information on sexual practices and sexual function. Combined with demographic, cancer, and treatment information from medical record abstraction, results of the Male Health Questionnaire were analyzed using multivariable modeling. The International Index of Erectile Function was used to identify ED in subjects. Main Outcome Measure: International Index of Erectile Function. Results: Survivors (mean age = 37.4 years, SD = 7.3 years) reported significantly lower sexual activity in the year before the survey than the brothers (mean age = 38.8 years, SD = 8.5 years) without cancer. ED was reported by 12.3% (95% CI = 10.4-14.3) of survivors and 4.2% (95% CI = 2.0-7.9) of brothers. Survivors showed significantly higher relative risk (RR) for ED (RR = 2.63, 95% CI = 1.40-4.97). In addition to older age, survivors who were exposed to higher-dose (≥10 Gy) testicular radiation (RR = 3.55, 95% CI = 1.53-8.24), had surgery on the spinal cord or nerves (RR = 2.87, 95% CI = 1.36-6.05), prostate surgery (RR = 6.56, 95% CI = 3.84-11.20), or pelvic surgery (RR = 2.28, 95% CI = 1.04-4.98) were at higher risk for ED. Conclusion: Men who have survived childhood cancer have a greater than 2.6-fold increased risk for ED and certain cancer-specific treatments are associated with increased risk. Attention to sexual health, with its physical and emotional implications, and opportunities for early detection and intervention in these individuals could be important.

Hematopoietic cell transplantation (HCT) is an important curative treatment for children with high-risk hematologic malignancies, solid tumors, and, increasingly, nonmalignant diseases. Given improvements in care, there are a growing number of long-term survivors of pediatric HCT. Compared with childhood cancer survivors who did not undergo transplantation, HCT survivors have a substantially increased burden of serious chronic conditions and impairments involving virtually every organ system and overall quality of life. This likely reflects the joint contributions of pretransplantation treatment exposures and organ dysfunction, the transplantation conditioning regimen, and any post-transplantation graft-versus-host disease (GVHD). In response, the Children's Oncology Group (COG) has created long-term follow-up guidelines (www.survivorshipguidelines.org) for survivors of childhood, adolescent, and young adult cancer, including those who were treated with HCT. Guideline task forces, consisting of HCT specialis ts, other pediatric oncologists, radiation oncologists, organ-specific subspecialists, nurses, social workers, other health care professionals, and patient advocates systematically reviewed the literature with regards to late effects after childhood cancer and HCT since 2002, with the most recent review completed in 2013. For the most recent review cycle, over 800 articles from the medical literature relevant to childhood cancer and HCT survivorship were reviewed, including 586 original research articles. Provided herein is an organ system-based overview that emphasizes the most relevant COG recommendations (with accompanying evidence grade) for the long-term follow-up care of childhood HCT survivors (regardless of current age) based on a rigorous review of the available evidence. These recommendations cover both autologous and allogeneic HCT survivors, those who underwent transplantation for nonmalignant diseases, and those with a history of chronic GVHD.

Infertility is known to decrease quality of life among adults. In some cases, infertility is caused by medical conditions and/or treatments prescribed in childhood, and using methods to protect or preserve fertility may expand future reproductive possibilities. Structured programs to offer counseling about infertility risk and fertility preservation options are essential in the care of pediatric patients facing fertility-threatening conditions or treatments, yet multiple barriers to program development exist. This report was developed from the institutional experiences of members of the Pediatric Initiative Network of the Oncofertility Consortium, with the intent of providing guidance for health care providers aiming to establish programs at institutions lacking pediatric fertility preservation services. The mechanics of building a fertility preservation program are discussed, including essential team members, target populations, fertility preservation options (both established and experimental), survivorship issues, research opportunities, and ethical considerations. Common barriers to program development and utilization, including low referral rates and financial concerns, are also discussed, and recommendations made for overcoming such barriers.

Purpose: To evaluate the relative contribution of modifiable cardiovascular risk factors on the development of major cardiac events in aging adult survivors of childhood cancer. Patients and Methods: Among 10,724 5-year survivors (median age, 33.7 years) and 3,159 siblings in the Childhood Cancer Survivor Study, the prevalence of hypertension, diabetes mellitus, dyslipidemia, and obesity was determined, along with the incidence and severity of major cardiac events such as coronary artery disease, heart failure, valvular disease, and arrhythmia. On longitudinal follow-up, rate ratios (RRs) of subsequent cardiac events associated with cardiovascular risk factors and cardiotoxic therapy were assessed in multivariable Poisson regression models. Results: Among survivors, the cumulative incidence of coronary artery disease, heart failure, valvular disease, and arrhythmia by 45 years of age was 5.3%, 4.8%, 1.5%, and 1.3%, respectively. Two or more cardiovascular risk factors were reported by 10.3% of survivors and 7.9% of siblings. The risk for each cardiac event increased with increasing number of cardiovascular risk factors (all Ptrend < .001). Hypertension significantly increased risk for coronary artery disease (RR, 6.1), heart failure (RR, 19.4), valvular disease (RR, 13.6), and arrhythmia (RR, 6.0; all P values < .01). The combined effect of chest-directed radiotherapy plus hypertension resulted in potentiation of risk for each of the major cardiac events beyond that anticipated on the basis of an additive expectation. Hypertension was independently associated with risk of cardiac death (RR, 5.6; 95% CI, 3.2 to 9.7). Conclusion: Modifiable cardiovascular risk factors, particularly hypertension, potentiate therapy-associated risk for major cardiac events in this population and should be the focus of future interventional studies.

Purpose: Many Childhood Cancer Survivor Study (CCSS) participants are at increased risk for obesity. The etiology of their obesity is likely multifactorial but not well understood. Patients and Methods: We evaluated the potential contribution of demographic, lifestyle, treatment, and intrapersonal factors and self-reported pharmaceutical use to obesity (body mass index ≥ 30 kg/m 2) among 9,284 adult (> 18 years of age) CCSS participants. Independent predictors were identified using multivariable regression models. Interrelationships were determined using structural equation modeling (SEM). Results: Independent risk factors for obesity included cancer diagnosed at 5 to 9 years of age (relative risk [RR], 1.12; 95% CI, 1.01 to 1.24; P = .03), abnormal Short Form-36 physical function (RR, 1.19; 95% CI, 1.06 to 1.33; P < .001), hypothalamic/pituitary radiation doses of 20 to 30 Gy (RR, 1.17; 95% CI, 1.05 to 1.30; P = .01), and paroxetine use (RR, 1.29; 95% CI, 1.08 to 1.54; P = .01). Meeting US Centers for Disease Control and Prevention guidelines for vigorous physical activity (RR, 0.90; 95% CI, 0.82 to 0.97; P = .01) and a medium amount of anxiety (RR, 0.86; 95% CI, 0.75 to 0.99; P = .04) reduced the risk of obesity. Results of SEM (N = 8,244; comparative fit index =0.999; Tucker Lewis index = 0.999; root mean square error of approximation = 0.014; weighted root mean square residual = 0.749) described the hierarchical impact of the direct predictors, moderators, and mediators of obesity. Conclusion: Treatment, lifestyle, and intrapersonal factors, as well as the use of specific antidepressants, may contribute to obesity among survivors. A multifaceted intervention, including alternative drug and other therapies for depression and anxiety, may be required to reduce risk.

The majority of children, adolescents, and young adults diagnosed with cancer will become long-term survivors. Although cancer therapy is associated with many adverse effects, one of the primary concerns of young male cancer survivors is reproductive health. Future fertility is often the focus of concern; however, it must be recognized that all aspects of male health, including pubertal development, testosterone production, and sexual function, can be impaired by cancer therapy. Although pretreatment strategies to preserve reproductive health have been beneficial to some male patients, many survivors remain at risk for long-term reproductive complications. Understanding risk factors and monitoring the reproductive health of young male survivors are important aspects of follow-up care. The Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancer (COG-LTFU Guidelines) were created by the COG to provide recommendations for follow-up care of survivors at risk for long-term complications. The male health task force of the COG-LTFU Guidelines, composed of pediatric oncologists, endocrinologists, nurse practitioners, a urologist, and a radiation oncologist, is responsible for updating the COG-LTFU Guidelines every 2 years based on literature review and expert consensus. This review summarizes current task force recommendations for the assessment and management of male reproductive complications after treatment for childhood, adolescent, and young adult cancers. Issues related to male health that are being investigated, but currently not included in the COG-LTFU Guidelines, are also discussed. Ongoing investigation will inform future COG-LTFU Guideline recommendations for follow-up care to improve health and quality of life for male survivors.

Background: The Children's Oncology Group (COG) publishes consensus guidelines with screening recommendations for early identification of treatment-related morbidities among childhood cancer survivors. We sought to estimate the yield of recommended yearly urinalysis screening for genitourinary complications as per Version 3.0 of the COG Long-Term Follow-Up Guidelines and identify possible risk factors for abnormal screening in a survivor population. Procedure: A database of pediatric cancer survivors evaluated between January 2008 and March 2012 at Children's Healthcare of Atlanta was queried for survivors at risk for genitourinary late effects. The frequency of abnormal urinalyses (protein ≥1+ and/or presence of glucose and/or ≥5 red blood cells per high power field) was estimated. Risk factors associated with abnormal screening were identified. Results: Chart review identified 773 survivors (57% male; 67% Caucasian; 60% leukemia/lymphoma survivors; mean age at diagnosis, 5.7 years [range: birth to 17.7 years]; time from diagnosis to initial screening, 7.6 years [range: 2.3 to 21.5 years]) who underwent urinalysis. Abnormal results were found in 78 (5.3%) of 1,484 total urinalyses. Multivariable analysis revealed higher dose ifosfamide (odds ratio [OR] = 6.8, 95% confidence interval [CI] 2.9-16.0) and total body irradiation (TBI, OR = 3.0, 95% CI 1.0-8.4) as significant risk factors for abnormal initial urinalysis screening. Conclusions: Pediatric cancer survivors exposed to higher dose ifosfamide or TBI may be at higher risk of abnormal findings on urinalysis screening. Targeted screening of these higher risk patients should be considered.

Once unimaginable, fertility management is now a nationally established part of cancer care in institutions, from academic centers to community hospitals to private practices. Over the last two decades, advances in medicine and reproductive science have made it possible for men, women and children to be connected with an oncofertility specialist or offered fertility preservation soon after a cancer diagnosis. The Oncofertility Consortium's National Physicians Cooperative is a large-scale effort to engage physicians across disciplines - oncology, urology, obstetrics and gynecology, reproductive endocrinology, and behavioral health - in clinical and research activities to enable significant progress in providing fertility preservation options to children and adults. Here, we review the structure and function of the National Physicians Cooperative and identify next steps.