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Data on hypothalamic-pituitary (HP) disorders in systematically evaluated childhood cancer survivors are limited.

Childhood cancer survivors experience chronic health conditions that impact health-related quality of life (HRQOL) and participation in optimal physical activity.

Guidelines are presented for the diagnosis and treatment of hypothalamic–pituitary and growth disorders in survivors of childhood cancer.

IMPORTANCE: Retinoblastoma survivors are at risk for adverse oculo-visual outcomes. Limited data are available regarding long-term vision-targeted health-related quality of life (HRQoL) of adult retinoblastoma survivors. OBJECTIVE: To examine vision-targeted HRQoL as reported on the 25-item National Eye Institute Visual Field Questionnaire for overall and specific scale scores among adult survivors of retinoblastoma. DESIGN, SETTING, AND PARTICIPANTS: The Retinoblastoma Survivor Study is a retrospective cohort of adult retinoblastoma survivors treated at 3 academic medical centers in New York between 1932 and 1994. Participants completed a comprehensive questionnaire between April 2008 and June 2010. Items were scored in January 2013 and preliminary analyses were performed in July 2015. Models were finalized in May 2017. MAIN OUTCOMES AND MEASURES: Self-reported vision-targeted HRQoL as reported on the 25-item National Eye Institute Visual Field Questionnaire. Items are scored from 0 to 100, with 100 representing the highest quality of life. RESULTS: Among 470 adult retinoblastoma survivors (53.6% with bilateral disease; 52.1% female; 86.4% white and non-Hispanic; mean age at study, 43.3 years; range, 18.0-77.0 years), 86% had at least 1 eye removed (1 eye, 74.5%; both eyes, 11.5%); 56.5% were previously treated with radiotherapy; and 61.3% rated their eyesight as excellent/good while 16.2% reported complete blindness. The overall mean (SD) VFQ composite score for all survivors was 81.1 (17.2) (mean [SD] score for unilateral retinoblastoma survivors, 91.4 [7.7]; bilateral retinoblastoma survivors, 72.3 [18.2]; difference between survivors with unilateral and bilateral disease, 19.1 [95% CI, 16.5-21.7; P < .001]). Prior exposure to radiotherapy was not associated with decreased overall VFQ (β = −0.08; 95% CI, −0.15 to 0.002; P = .06) but was related to a few specific subdomains of visual functioning. CONCLUSIONS AND RELEVANCE: These findings suggest retinoblastoma-related oculo-visual problems are associated with functional status and vision-targeted HRQoL of adult survivors, particularly among those with bilateral disease.

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We report on the prevalence, risk factors, and consequences on general health of premature ovarian insufficiency in a cohort of 921 long-term survivors of childhood cancers.

Reproductive health and fertility are of great importance to the increasing number of survivors of childhood cancer, approximately 70% of whom are estimated to be over 20 years old. This article reviews the various treatment exposures that have been associated with makers of gonadal injury and decreased fertility in childhood cancer survivors. Identifying risk factors that decrease fertility is essential in proper counseling and timely referral for interventions that may allow for future fertility in high-risk populations.

5 year survival for childhood and adolescent cancer in developed countries is now in excess of 80% and the number of survivors of cancer continues to increase worldwide. After completion of therapy, many of these survivors will face a lifelong risk of endocrine late effects. We summarise the available evidence related to the prevalence and risk factors for endocrine late effects among adult survivors of childhood and adolescent cancer. Present screening, surveillance, and treatment recommendations differ by country and region, so we also highlight the continued effort to harmonise the international guidelines for this population.

Context:GH and IGF-1 have been shown to affect tumor growth in vitro and in some animal models. This report summarizes the available evidence on whether GH therapy in childhood is associated with an increased risk of neoplasia during treatment or after treatment is completed.Evidence Acquisition:A PubMed search conducted through February 2014 retrieved original articles written in English addressing GH therapy and neoplasia risk. Subsequent searches were done to include additional relevant publications.Evidence Synthesis:In children without prior cancer or known risk factors for developing cancer, the clinical evidence does not affirm an association between GH therapy during childhood and neoplasia. GH therapy has not been reported to increase the risk for neoplasia in this population, although most of these data are derived from postmarketing surveillance studies lacking rigorous controls. In patients who are at higher risk for developing cancer, current evidence is insufficient to conclude whether or not GH further increases cancer risk. GH treatment of pediatric cancer survivors does not appear to increase the risk of recurrence but may increase their risk for subsequent primary neoplasms.Conclusions:In children without known risk factors for malignancy, GH therapy can be safely administered without concerns about an increased risk for neoplasia. GH use in children with medical diagnoses predisposing them to the development of malignancies should be critically analyzed on an individual basis, and if chosen, appropriate surveillance for malignancies should be undertaken. GH can be used to treat GH-deficient childhood cancer survivors who are in remission with the understanding that GH therapy may increase their risk for second neoplasms.

To assess testicular function after standard dose ifosfamide, we evaluated 6 young adult osteosarcoma survivors (median age at diagnosis, 16.5 y; median follow-up, 4 y) treated with ifosfamide (median dose, 45.5 gm2) as part of a chemotherapy regimen (adriamycincisplatinmethotrexateifosfamide±muramyl-tripeptide-phosphatidyl-ethanolamine). Four of 6 survivors (67) had abnormal semen analysis (2 oligospermic, 2 azoospermic). Of those, 14 had reduced testicular volume, and 23 elevated FSH levels. All reported adequate sexual function, 66 had normal testosterone levels, but 46 had elevated LH levels. Ifosfamide exposure in the context of this regimen was associated with a high likelihood of impaired spermatogenesis and Leydig cell insufficiency.

Survivors of childhood acute lymphoblastic leukemia (ALL) have an increased risk of cardiovascular disease. Small density lipoproteins are atherogenic but have not been studied in this population. We conducted a cross-sectional analysis of 110 ALL survivors (mean age, 24.3 years) to determine prevalence of small dense LDL (pattern B) phenotype in ALL survivors and identify associated factors. Lipid subfractions were measured using Vertical Auto Profile-II. Participants with greater than 50% of LDL-cholesterol (LDL-c) in small dense LDL fractions (LDL3+4) were classified as LDL pattern B. Visceral and subcutaneous adipose tissue (VAT, SAT) volumes were also measured by computed tomography. While the mean LDL-c level of ALL survivors was 108.7 ± 26.8 mg/dl, 36% (40/110) of survivors had atherogenic LDL pattern B. This pattern was more common in males (26/47; 55%) than in females (14/63; 22%, P= 0.001) and more common in survivors treated with cranial radiotherapy (15/33; 45%) than in those who were treated with chemotherapy alone (25/77; 33%; P= 0.04, adjusted for age, gender, history of hypertension, and smoking history). VAT was associated with atherogenic lipids: LDL pattern B and LDL3+4levels. This association was independent of other measures of body fat. We conclude that a substantial proportion of ALL survivors had an atherogenic LDL phenotype despite normal mean LDL-c levels. An atherogenic LDL phenotype may contribute to the increase in cardiovascular mortality and morbidity in this population.

HSCT is being increasingly offered as a curative option for children with hematologic malignancies. Although survival has improved, the long-term morbidity ascribed to the HSCT procedure is not known. We compared the risk of chronic health conditions and adverse health among children with cancer treated with HSCT with survivors treated conventionally, as well as with sibling controls. HSCT survivors were drawn from BMTSS (N = 145), whereas conventionally treated survivors (N = 7207) and siblings (N = 4020) were drawn from CCSS. Self-reported chronic conditions were graded with CTCAEv3.0. Fifty-nine percent of HSCT survivors reported ≥ 2 conditions, and 25.5% reported severe/life-threatening conditions. HSCT survivors were more likely than sibling controls to have severe/life-threatening (relative risk [RR] = 8.1, P< .01) and 2 or more (RR = 5.7, P< .01) conditions, as well as functional impairment (RR = 7.7, P< .01) and activity limitation (RR = 6.3, P< .01). More importantly, compared with CCSS survivors, BMTSS survivors demonstrated significantly elevated risks (severe/life-threatening conditions: RR = 3.9, P< .01; multiple conditions: RR = 2.6, P< .01; functional impairment: RR = 3.5, P< .01; activity limitation: RR = 5.8, P< .01). Unrelated donor HSCT recipients were at greatest risk. Childhood HSCT survivors carry a significantly greater burden of morbidity not only compared with noncancer populations but also compared with conventionally treated cancer patients, providing evidence for close monitoring of this high-risk population.

HSCT is being increasingly offered as a curative option for children with hematologic malignancies. Although survival has improved, the long-term morbidity ascribed to the HSCT procedure is not known. We compared the risk of chronic health conditions and adverse health among children with cancer treated with HSCT with survivors treated conventionally, as well as with sibling controls. HSCT survivors were drawn from BMTSS (N = 145), whereas conventionally treated survivors (N = 7207) and siblings (N = 4020) were drawn from CCSS. Self-reported chronic conditions were graded with CTCAEv3.0. Fifty-nine percent of HSCT survivors reported ≥ 2 conditions, and 25.5% reported severe/life-threatening conditions. HSCT survivors were more likely than sibling controls to have severe/life-threatening (relative risk [RR] = 8.1, P < .01) and 2 or more (RR = 5.7, P < .01) conditions, as well as functional impairment (RR = 7.7, P < .01) and activity limitation (RR = 6.3, P < .01). More importantly, compared with CCSS survivors, BMTSS survivors demonstrated significantly elevated risks (severe/life-threatening conditions: RR = 3.9, P < .01; multiple conditions: RR = 2.6, P < .01; functional impairment: RR = 3.5, P < .01; activity limitation: RR = 5.8, P < .01). Unrelated donor HSCT recipients were at greatest risk. Childhood HSCT survivors carry a significantly greater burden of morbidity not only compared with noncancer populations but also compared with conventionally treated cancer patients, providing evidence for close monitoring of this high-risk population.

We ascertained the prevalence of self-reported late occurrence of diabetes, hypertension, and cardiovascular (CV) disease in 1089 hematopoietic cell transplantation (HCT) survivors who underwent HCT between 1974 and 1998, survived at least 2 years, and were not currently taking immunosuppressant agents and compared them with 383 sibling controls. All subjects completed a 255-item health questionnaire. The mean age at survey completion was 39.3 years for survivors and 38.6 years for siblings; mean follow-up was 8.6 years. Adjusting for age, sex, race, and body mass index (BMI), survivors of allogeneic HCT were 3.65 times (95% confidence interval [CI], 1.82-7.32) more likely to report diabetes than siblings and 2.06 times (95% CI, 1.39-3.04) more likely to report hypertension compared with siblings but did not report other CV outcomes with any greater frequency. Recipients of autologous HCTs were no more likely than siblings to report any of the outcomes studied. Allogeneic HCT survivors were also more likely to develop hypertension (odds ratio [OR] = 2.31; 95% CI, 1.45-3.67) than autologous recipients. Total body irradiation (TBI) exposure was associated with an increased risk of diabetes (OR = 3.42; 95% CI, 1.55-7.52). Thus, HCT survivors have a higher age- and BMI-adjusted risk of diabetes and hypertension, potentially leading to a higher than expected risk of CV events with age.

We ascertained the prevalence of self-reported late occurrence of diabetes, hypertension, and cardiovascular (CV) disease in 1089 hematopoietic cell transplantation (HCT) survivors who underwent HCT between 1974 and 1998, survived at least 2 years, and were not currently taking immunosuppressant agents and compared them with 383 sibling controls. All subjects completed a 255-item health questionnaire. The mean age at survey completion was 39.3 years for survivors and 38.6 years for siblings; mean follow-up was 8.6 years. Adjusting for age, sex, race, and body mass index (BMI), survivors of allogeneic HCT were 3.65 times (95% confidence interval [CI], 1.82-7.32) more likely to report diabetes than siblings and 2.06 times (95% CI, 1.39-3.04) more likely to report hypertension compared with siblings but did not report other CV outcomes with any greater frequency. Recipients of autologous HCTs were no more likely than siblings to report any of the outcomes studied. Allogeneic HCT survivors were also more likely to develop hypertension (odds ratio [OR] = 2.31; 95% CI, 1.45-3.67) than autologous recipients. Total body irradiation (TBI) exposure was associated with an increased risk of diabetes (OR = 3.42; 95% CI, 1.55-7.52). Thus, HCT survivors have a higher age- and BMI-adjusted risk of diabetes and hypertension, potentially leading to a higher than expected risk of CV events with age.

During the past 30 years, changes in the treatment of children and adolescents with cancer have led to substantial improvements in survival. Although treatment‐related factors have been shown to impact subsequent health status and quality of life, there is limited information on survivors who are now two or more decades after treatment. The Childhood Cancer Survivor Study (CCSS) was established as a resource for investigating the long‐term outcomes of a cohort of 5‐year survivors of childhood and adolescent cancer, diagnosed between 1970–1986. The CCSS cohort has more than 14,000 active participants, including survivors of leukemia, brain tumors, Hodgkin disease, non‐Hodgkin lymphoma, Wilms tumor, neuroblastoma, soft‐tissue sarcoma, and bone tumors. Study participants, extensively characterized by their cancer therapy, have provided self‐reported sociodemographic‐ and health‐related information. Although the survivor population has been found to be at significantly increased risk of several adverse outcomes, such as late mortality, second cancers, pulmonary complications, pregnancy loss, low birth weight of offspring, and decreased education, the overall proportion of survivors affected is relatively small. Subgroups at high risk of adverse outcomes, defined by treatment‐related, demographic, or medical factors, can be identified. The ongoing evaluation of large and diverse cohorts of cancer survivors will aid in further identifying individuals who should be the target of innovative intervention strategies. Cancer 2005. © 2005 American Cancer Society.

The goals of the current study were to determine the distribution of body mass index (BMI) of survivors of common pediatric malignancies and to identify factors associated with abnormal BMI.The Childhood Cancer Survivor Study (CCSS) is a multicenter cohort study of ≥ 5‐year survivors of pediatric cancer diagnosed between 1970 and 1986. Self‐reported heights and weights were used to calculate BMI for 7195 adult survivors, compared with population‐based, age‐specific, and gender‐specific norms from the 1995 National Health Interview Survey. Underweight was defined as a BMI < 18.5 kg/m2 and obese as BMI ≥ 30 kg/m2.Survivors of leukemia were more likely to be obese (females: odds ratio [OR] = 1.5; 95% confidence interval [CI], 1.2–1.8; males: OR = 1.2; 95% CI, 1.0–1.5). Survivors more likely to be underweight included female and male survivors of Hodgkin disease (OR = 1.7; 95% CI, 1.3–2.3 and OR = 3.5; 95% CI, 2.3–5.3) and Wilms tumor (OR = 1.8; 95% CI, 1.2–2.8 and OR = 5.5; 95% CI, 3.1–9.7), female survivors of bone carcinoma without amputation (OR = 1.9; 95% CI, 1.2–2.9), and male survivors of leukemia (OR = 2.4; 95% CI, 1.6–3.6), brain tumors (OR = 2.7; 95% CI, 1.6–4.4), non‐Hodgkin lymphoma (OR = 3.1; 95% CI, 1.9–5.2), neuroblastoma (OR = 4.9; 95% CI, 2.48–10.0), and soft tissue sarcoma (OR = 3.5; 95% CI, 2.0–6.0). In females, treatment with total body irradiation, alkylating agents, and anthracyclines and in males, treatment with abdominal radiation, younger age at treatment, and treatment with anthracyclines and alkylating agents were associated with being underweight. Underweight survivors were more likely to report adverse health and major medical conditions.A significant proportion of childhood survivors of cancer are underweight as adults and the impact of this on the general health of survivors will need to be addressed further. Cancer 2005. © 2005 American Cancer Society.