A B S T R A C T PurposeTo 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 MethodsAmong 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. ResultsAmong 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 P trend Ͻ .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 Ͻ .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). ConclusionModifiable 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.

Laron-type dwarfism is an autosomal recessive genetic disorder that is characterized by high levels of growth hormone and low levels of insulin-like growth factor I in the circulation. Several lines of evidence suggest that this disease is caused by a defect in the growth hormone receptor. In order to analyze the receptor gene in patients with Laron-

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Background: Childhood cancer survivors are at higher risk of morbidity and mortality from cardiovascular disease compared with the general population.Methods: Eight thousand five hundred ninety-nine survivors (52% male) and 2,936 siblings (46% male) from the Childhood Cancer Survivor Study, a retrospectively ascertained, prospectively followed study of persons who survived 5 years after childhood cancer diagnosed from 1970 to 1986, were evaluated for body mass index of ≥30 kg/m 2 based on self-reported heights and weights and self-reported use of medications for

The development of curative therapy for most pediatric malignancies has produced a growing population of childhood cancer survivors who are at increased risk for a variety of health problems resulting from their cancer or its treatment. Because of the fact that many treatment-related sequelae may not become clinically apparent until the survivor attains maturity or begins to age, the ability of primary care providers to anticipate late effects of treatment is essential for providing timely interventions that prevent or correct these sequelae and their adverse effects on quality of life. Altered bone metabolism during treatment for childhood cancer may interfere with attainment of peak bone mass, potentially predisposing to premature onset of and more severe complications related to osteopenia and osteoporosis. Bone mineral deficits have been reported after treatment for a variety of pediatric malignancies and represent morbidity that can be reduced or prevented through lifestyle changes and attention to other common cancer-related sequelae such as hypogonadism. The Children's Oncology Group long-term follow-up guidelines for survivors of childhood, adolescent, and young adult cancers provide risk-based surveillance recommendations that are based on expert opinion and review of the scientific literature for potential late effects of pediatric cancer therapy including osteopenia. This review summarizes the existing literature that has defined characteristics of cancer survivors at risk for bone mineral deficits and contributed to the surveillance and counseling recommendations outlined in the Children's Oncology group long-term follow-up guidelines.

Due to remarkable improvements in childhood cancer treatment and supportive care during the past several decades, 5-year survival rates for childhood cancer currently are >80%. However, by virtue of their disease and its treatments, childhood cancer survivors are at increased risk for a wide range of serious health conditions, including disorders of the endocrine system. Recent data indicate that 40% to 50% of survivors will develop an endocrine disorder during their lifetime. Risk factors for endocrine complications include both host (e.g., age, sex) and treatment factors (e.g., radiation). Radiation exposure to key endocrine organs (e.g., hypothalamus, pituitary, thyroid, and gonads) places cancer survivors at the highest risk of developing an endocrine abnormality over time; these endocrinopathies can develop decades following cancer treatment, underscoring the importance of lifelong surveillance. The following guideline addresses the diagnosis and treatment of hypothalamic-pituitary and growth disorders commonly encountered in childhood cancer survivors.

A B S T R A C T PurposeWe examined the rate of increase in the body mass index (BMI; kg/m 2 ) after final height attainment in survivors of acute lymphoblastic leukemia (ALL) and a noncancer comparison group. MethodsChildhood Cancer Survivor Study (CCSS) is a retrospectively ascertained cohort study that prospectively tracks the health status of adults who were diagnosed with childhood cancer between 1970 and 1986 and a comparison group of siblings. Changes in BMI from baseline enrollment to time of completion of follow-up (mean interval, 7.8 years) were calculated for 1,451 ALL survivors (mean age, 32.3 years at follow-up) and 2,167 siblings of childhood cancer survivors (mean age, 35.9 years). ResultsThe mean BMI of the CCSS sibling comparison group increased with age (women, 0.25 units/yr, 95% CI, 0.22 to 0.28 units; men, 0.23 units/yr, 95% CI, 0.20 to 0.25 units). Compared with CCSS siblings, ALL survivors who were treated with cranial radiation therapy (CRT) had a significantly greater increase in BMI (women, 0.41 units/yr, 95% CI, 0.37 to 0.45 units; men, 0.29 units/yr; 95% CI, 0.26 to 0.32 units). The rate of BMI increase was not significantly increased for ALL survivors who were treated with chemotherapy alone. Younger age at CRT exposure significantly modified risk. ConclusionCRT used in the treatment of childhood ALL is associated with a greater rate of increasing BMI, particularly among women treated with CRT during the first decade of life. Health care professionals should be aware of this risk and interventions to reduce or manage weight gain are essential in this high-risk population.

BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.