Attributable Risk and Consequences of Bone Mineral Density Deficits in Childhood Cancer Survivors.

Importance: Data characterizing the severity and changing prevalence of bone mineral density (BMD) deficits and associated nonfracture consequences among childhood cancer survivors decades after treatment are lacking.

Objective: To evaluate risk for moderate and severe BMD deficits in survivors and to identify long-term consequences of BMD deficits.

Design, Setting, And Participants: This cohort study used cross-sectional and longitudinal data from the St Jude Lifetime (SJLIFE) cohort, a retrospectively constructed cohort with prospective follow-up.

Diagnostic Utility of Low-Dose Cosyntropin Stimulation Test for Central Adrenal Insufficiency.

Introduction: Consensus regarding the diagnostic cutoff values for cortisol responses to low-dose Cosyntropin testing (LDT) and its specific advantages over standard (high) dose test (HDT) in assessing the pituitary-adrenal axis in children is lacking.

Methods: In a retrospective study, patients who underwent sequential LDT and HDT were classified into two groups depending on the reason for testing: prolonged systemic glucocorticoid exposure (Group 1) or suspected hypothalamic-pituitary dysfunction (Group 2). Sensitivity and specificity analysis of varying cortisol levels during LDT in diagnosing ACTH deficiency (ACTHD) were calculated via the receiver operating characteristic curve (ROC) analysis against the reference diagnostic test HDT.

Hypogonadism and neurocognitive outcomes among childhood cancer survivors.

Objective: Childhood cancer survivors are at risk for hypogonadism. The impact of hypogonadism on neurocognitive impairment and emotional distress in the non-cancer population has been shown; however, the relationship among the childhood cancer survivor population is unknown. We aimed to evaluate the contribution of hypogonadism to neurocognitive impairment and emotional distress among survivors.

Prediabetes and Associated Risk of Cardiovascular Events and Chronic Kidney Disease Among Adult Survivors of Childhood Cancer in the St Jude Lifetime Cohort.

Purpose: Little is known about the prevalence of prediabetes and associated risk of cardiovascular events and chronic kidney disease (CKD) with this reversable condition in survivors.

Methods: Prevalence of prediabetes (fasting plasma glucose 100-125 mg/dL or hemoglobin A1c 5.7%-6.

Association of Modifiable Health Conditions and Social Determinants of Health With Late Mortality in Survivors of Childhood Cancer.

Importance: Associations between modifiable chronic health conditions (CHCs), social determinants of health, and late mortality (defined as death occurring ≥5 years after diagnosis) in childhood cancer survivors are unknown.

Objective: To explore associations between modifiable CHCs and late mortality within the context of social determinants of health.

Design, Setting, And Participants: This longitudinal cohort study used data from 9440 individuals who were eligible to participate in the St Jude Lifetime Cohort (SJLIFE), a retrospective cohort study with prospective clinical follow-up that was initiated in 2007 to characterize outcomes among childhood cancer survivors.

Premature aging as an accumulation of deficits in young adult survivors of pediatric cancer.

Background: We aimed to characterize premature aging as an accumulation of deficits in survivors of pediatric cancer compared with community controls and examine associations with host and treatment factors, neurocognition, and mortality.

Methods: Pediatric cancer survivors (n = 4000, median age = 28.6, interquartile range [IQR] = 23-35 years; 20 years postdiagnosis: IQR = 15-27), and community participants without a history of cancer serving as controls (n = 638, median age = 32, IQR = 25-40 years) completed clinical assessments and questionnaires and were followed for mortality through April 30, 2020 (mean [SD] follow-up = 7.

Hormone replacement in survivors of childhood cancer and brain tumors: safety and controversies.

Childhood cancer survivors are at risk for developing endocrine disorders, including deficits in growth hormone, thyroid hormone and sex hormones. The influence these hormones have on cell growth and metabolism has raised concerns regarding the safety of their use as treatments in survivors of childhood cancer and brain tumors. This article offers a summary of current knowledge, controversies and areas for future research pertaining to this area.

Clinical Assessment of Late Health Outcomes in Survivors of Wilms Tumor.

Objectives: We aimed to clinically characterize the health, neurocognitive, and physical function outcomes of curative treatment of Wilms tumor.

Methods: Survivors of Wilms tumor (n = 280) participating in the St. Jude Lifetime Cohort, a retrospective study with prospective follow-up of individuals treated for childhood cancer at St.

Design and methods of a randomized web-based physical activity intervention among children with cancer: A report from the Children's Oncology Group.

Background: Promoting physical activity soon after treatment for childhood cancer may benefit health because sedentary lifestyle during curative therapy may perpetuate physical and emotional complications. The primary goals of this study are to evaluate the effects of a 6-month web-based, rewards-based physical activity intervention on fitness, biomarkers of cardiometabolic health, inflammation, adipokine status, quality of life and school attendance, and determine if effect of intervention on markers of cardiometabolic health is mediated by changes in fitness. The primary outcome of interest is fitness (physiological cost index, six-minute walk test) measured at end of intervention.

Management of childhood cancer survivors at risk for thyroid function abnormalities: A Delphi study.

Background: Thyroid function abnormalities can occur after treatment for childhood cancer. Evidence for the management of thyroid dysfunction among asymptomatic childhood cancer survivors (CCS) is lacking. We used a Delphi consensus methodology to expand guidelines for screening asymptomatic CCS at risk for thyroid dysfunction and explore recommendations for the clinical management of abnormal results.

Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary tumours: a consensus statement.

Growth hormone (GH) has been used for over 35 years, and its safety and efficacy has been studied extensively. Experimental studies showing the permissive role of GH/insulin-like growth factor 1 (IGF-I) in carcinogenesis have raised concerns regarding the safety of GH replacement in children and adults who have received treatment for cancer and those with intracranial and pituitary tumours. A consensus statement was produced to guide decision-making on GH replacement in children and adult survivors of cancer, in those treated for intracranial and pituitary tumours and in patients with increased cancer risk.

Primary hypothyroidism in childhood cancer survivors: Prevalence, risk factors, and long-term consequences.

Background: Data on primary hypothyroidism and its long-term impact on the health, cognition, and quality of life (QOL) of childhood cancer survivors are limited. This study examined the prevalence of and risk factors for primary hypothyroidism and its associations with physical, neurocognitive, and psychosocial outcomes.

Methods: This was a retrospective study with a cross-sectional health outcome analysis of an established cohort comprising 2965 survivors of childhood cancer (52.

Safety of growth hormone (GH) treatment in GH deficient children and adults treated for cancer and non-malignant intracranial tumors-a review of research and clinical practice.

Individuals surviving cancer and brain tumors may experience growth hormone (GH) deficiency as a result of tumor growth, surgical resection and/or radiotherapy involving the hypothalamic-pituitary region. Given the pro-mitogenic and anti-apoptotic properties of GH and insulin-like growth factor-I, the safety of GH replacement in this population has raised hypothetical safety concerns that have been debated for decades. Data from multicenter studies with extended follow-up have generally not found significant associations between GH replacement and cancer recurrence or mortality from cancer among childhood cancer survivors.

Progression of Frailty in Survivors of Childhood Cancer: A St. Jude Lifetime Cohort Report.

Background: Some adult survivors of childhood cancers develop frailty at higher rates than expected based on their chronological age. This study examined the incidence of frailty among survivors at 10 or more years after diagnosis, frailty prevalence 5 years later, and risk factors for becoming frail.

Methods: Frailty was measured at study entry and 5 years later.

Possible modification of BRSK1 on the risk of alkylating chemotherapy-related reduced ovarian function.

Study Question: Do genetic variations in the DNA damage response pathway modify the adverse effect of alkylating agents on ovarian function in female childhood cancer survivors (CCS)?

Summary Answer: Female CCS carrying a common BR serine/threonine kinase 1 (BRSK1) gene variant appear to be at 2.5-fold increased odds of reduced ovarian function after treatment with high doses of alkylating chemotherapy.

What Is Known Already: Female CCS show large inter-individual variability in the impact of DNA-damaging alkylating chemotherapy, given as treatment of childhood cancer, on adult ovarian function.

Hypothalamic-Pituitary Dysfunctions Other Than Growth Hormone Deficiency in Cancer Survivors.

Hypothalamic-pituitary (HP) dysfunctions are commonly reported complications in survivors of childhood cancer. These include growth hormone deficiency, luteinizing hormone/follicle-stimulating hormone deficiency, thyroid-stimulating hormone deficiency, adrenocorticotropic hormone deficiency, central precocious puberty, hyperprolactinemia, and central diabetes insipidus. Local tumor invasion and surgical or radiation-induced injury represent the highest risk factors.

Late outcomes in survivors of childhood acute myeloid leukemia: a report from the St. Jude Lifetime Cohort Study.

Cumulative burden of chronic health conditions and neurocognitive and physical function were examined among survivors of childhood acute myeloid leukemia (AML) treated with hematopoietic cell transplant (HCT; n = 66) or conventional therapy (CT; n = 67). Survivors and controls underwent a comprehensive clinical assessment, and health conditions were graded using a modified version of the Common Terminology Criteria for Adverse Events. By age 40 years, HCT and CT survivors had an average 17.

Genome-wide Association Studies Reveal Novel Locus With Sex-/Therapy-Specific Fracture Risk Effects in Childhood Cancer Survivors.

Childhood cancer survivors treated with radiation therapy (RT) and osteotoxic chemotherapies are at increased risk for fractures. However, understanding of how genetic and clinical susceptibility factors jointly contribute to fracture risk among survivors is limited. To address this gap, we conducted genome-wide association studies of fracture risk after cancer diagnosis in 2453 participants of European ancestry from the Childhood Cancer Survivor Study (CCSS) with 930 incident fractures using Cox regression models (ie, time-to-event analysis) and prioritized sex- and treatment-stratified genetic associations.

Childhood Neurotoxicity and Brain Resilience to Adverse Events during Adulthood.

Objective: This study used childhood cancer survivors as a novel model to study whether children who experience central nervous system (CNS) injury are at higher risk for neurocognitive impairment associated with subsequent late onset chronic health conditions (CHCs).

Methods: Adult survivors of childhood cancer (n = 2,859, ≥10 years from diagnosis, ≥18 years old) completed a comprehensive neurocognitive battery and clinical examination. Neurocognitive impairment was defined as age-adjusted z score < 10th percentile.

Endocrine Health in Childhood Cancer Survivors.

Endocrine late effects, including reproductive disorders and secondary thyroid cancer, have been reported in up to 50 %childhood cancer survivors (CCS) more than 5 years after treatment. Most endocrine disorders are amenable to treatment; awareness of symptoms is therefore of great importance. Recognition of these symptoms may be delayed however because many are nonspecific.

Clinical impact of hypothalamic-pituitary disorders after conformal radiation therapy for pediatric low-grade glioma or ependymoma.

Background: To determine the impact of hypothalamic-pituitary (HP) disorders on health outcomes in children and adolescents who received conformal radiation therapy (RT) for central nervous system tumors.

Procedure: Cohort study including 355 patients (age ≤25 years at diagnosis) treated with high-dose (50.4-59.

Generalizability of "GWAS Hits" in Clinical Populations: Lessons from Childhood Cancer Survivors.

With mounting interest in translating genome-wide association study (GWAS) hits from large meta-analyses (meta-GWAS) in diverse clinical settings, evaluating their generalizability in target populations is crucial. Here, we consider long-term survivors of childhood cancers from the St. Jude Lifetime Cohort Study, and we show the limited generalizability of 1,376 robust SNP associations reported in the general population across 12 complex anthropometric and cardiometabolic phenotypes (n = 2,231; observed-to-expected replication ratio = 0.

Body Composition, Metabolic Health, and Functional Impairment among Adults Treated for Abdominal and Pelvic Tumors during Childhood.

Background: We aimed to characterize body composition, metabolic impairments, and physical performance among survivors of pediatric abdominal and pelvic solid tumors.

Methods: Participants included 431 survivors of abdominal or pelvic tumors [median attained age = 29.9 (range: 18.