Briana C. Patterson

Female Reproductive Health After Childhood, Adolescent, and Young Adult Cancers: Guidelines for the Assessment and Management of Female Reproductive Complications

PURPOSE As more young female patients with cancer survive their primary disease, concerns about reproductive health related to primary therapy gain relevance. Cancer therapy can often affect reproductive organs, leading to impaired pubertal development, hormonal regulation, fertility, and sexual function, affecting quality of life. METHODS The Childrens Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancer (COG-LTFU Guidelines) are evidence-based recommendations for screening and management of late effects of therapeutic exposures. The guidelines are updated every 2 years by a multidisciplinary panel based on current literature review and expert consensus. RESULTS This review summarizes the current task force recommendations for the assessment and management of female reproductive complications after treatment for childhood, adolescent, and young adult cancers. Experimental pretreatment as well as post-treatment fertility preservation strategies, including barriers and ethical considerations, which are not included in the COG-LTFU Guidelines, are also discussed. CONCLUSION Ongoing research will continue to inform COG-LTFU Guideline recommendations for follow-up care of female survivors of childhood cancer to improve their health and quality of life.

Growth Hormone Exposure as a Risk Factor for the Development of Subsequent Neoplasms of the Central Nervous System: A Report From the Childhood Cancer Survivor Study

CONTEXT Cranial radiation therapy (CRT) predisposes to GH deficiency and subsequent neoplasms (SNs) of the central nervous system (CNS). Increased rates of SNs have been reported in GH-treated survivors. OBJECTIVE The objective of the study was to evaluate the association between GH treatment and the development of CNS-SNs. DESIGN The study was designed with a retrospective cohort with longitudinal follow-up. SETTING The setting of the study was multiinstitutional. PARTICIPANTS A total of 12 098 5-year pediatric cancer survivors from the Childhood Cancer Survivor Study, diagnosed with cancer prior to age 21 years, of whom 338 self-reported GH treatment, which was verified through medical record review. INTERVENTIONS INTERVENTIONS included subject surveys, medical records abstraction, and pathological review. OUTCOME MEASURES Incidence of meningioma, glioma, and other CNS-SNs was measured. RESULTS Among GH-treated survivors, 16 (4.7%) developed CNS-SN, including 10 with meningioma and six with glioma. Two hundred three survivors without GH treatment (1.7%) developed CNS-SN, including 138 with meningioma, 49 with glioma, and 16 with other CNS-SNs. The adjusted rate ratio in GH-treated compared with untreated survivors for development of any CNS-SN was 1.0 [95% confidence interval (CI) 0.6-1.8, P = .94], for meningiomas, 0.8 (95% CI 0.4-1.7, P = .61), and for gliomas, 1.9 (95% CI 0.7-4.8, P = .21). Factors associated with meningioma development included female gender (P = .001), younger age at primary cancer diagnosis (P < .001), and CRT/longer time since CRT (P < .001). Glioma was associated with CRT/shorter time since CRT (P < .001). CONCLUSIONS There was no statistically significant increased overall risk of the occurrence of a CNS-SN associated with GH exposure. Specifically, occurrence of meningiomas and gliomas were not associated with GH treatment.

Risk of Neoplasia in Pediatric Patients Receiving Growth Hormone Therapy--A Report From the Pediatric Endocrine Society Drug and Therapeutics Committee.

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.

Endocrine health problems detected in 519 patients evaluated in a pediatric cancer survivor program.

CONTEXT Many pediatric cancer survivors have endocrine conditions. Surveillance for late effects is recommended by national guidelines. Endocrine surveillance is recommended after alkylating agents, steroids, methotrexate, and radiation. OBJECTIVE The objective of the study was to describe the endocrine outcomes in patients followed up in a program that uses national screening guidelines. DESIGN The design of the study was a medical records review. SETTING The study was conducted in the Comprehensive Cancer Survivor Program, an academic pediatric oncology program. PARTICIPANTS The study included 519 pediatric and young adult survivors of noncentral nervous system childhood malignancies between January 1, 2001, and December 15, 2005. INTERVENTION Patients were evaluated with history, physical examinations, and evaluations recommended in the Childrens Oncology Groups Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent and Young Adult Cancers. OUTCOME MEASURES The frequency and types of endocrine conditions were measured. RESULTS Four hundred eighty endocrine conditions were observed in 299 survivors (57.6% of survivors). The most common types of endocrine conditions were problems with weight and gonadal function. In a Cox regression model, stem cell transplant, radiation, and older age at cancer diagnosis were associated with higher hazard of an endocrine condition. Radiation, stem cell transplant, and sarcoma diagnosis were associated with growth problems. CONCLUSIONS Endocrine disorders were common after pediatric cancers. Endocrinologists should be aware of national guidelines, anticipate referral of pediatric cancer survivors, and participate in further research to optimize screening for and treatment of endocrine effects of cancer therapy.

Adrenal function testing in pediatric cancer survivors.

Central adrenal insufficiency is observed after cranial radiation therapy for cancer. Screening at risk patients is recommended, but the best screening strategy is unknown.

Endocrine outcomes with proton and photon radiotherapy for standard risk medulloblastoma

BACKGROUND Endocrine dysfunction is a common sequela of craniospinal irradiation (CSI). Dosimetric data suggest that proton radiotherapy (PRT) may reduce radiation-associated endocrine dysfunction but clinical data are limited. METHODS Seventy-seven children were treated with chemotherapy and proton (n = 40) or photon (n = 37) radiation between 2000 and 2009 with ≥3 years of endocrine screening. The incidence of multiple endocrinopathies among the proton and photon cohorts is compared. Multivariable analysis and propensity score adjusted analysis are performed to estimate the effect of radiotherapy type while adjusting for other variables. RESULTS The median age at diagnosis was 6.2 and 8.3 years for the proton and photon cohorts, respectively (P = .010). Cohorts were similar with respect to gender, histology, CSI dose, and total radiotherapy dose and whether the radiotherapy boost was delivered to the posterior fossa or tumor bed. The median follow-up time was 5.8 years for proton patients and 7.0 years for photon patients (P = .010). PRT was associated with a reduced risk of hypothyroidism (23% vs 69%, P < .001), sex hormone deficiency (3% vs 19%, P = .025), requirement for any endocrine replacement therapy (55% vs 78%, P = .030), and a greater height standard deviation score (mean (± SD) -1.19 (± 1.22) vs -2 (± 1.35), P = .020) on both univariate and multivariate and propensity score adjusted analysis. There was no significant difference in the incidence of growth hormone deficiency (53% vs 57%), adrenal insufficiency (5% vs 8%), or precocious puberty (18% vs 16%). CONCLUSIONS Proton radiotherapy may reduce the risk of some, but not all, radiation-associated late endocrine abnormalities.

Severity of health conditions identified in a pediatric cancer survivor program.

The Common Terminology Criteria for Adverse Events v3.0 (CTCAE) was designed for reporting acute and late effects of cancer treatment. To date, no study of pediatric‐aged cancer survivors has graded health conditions using CTCAE, for patients in active follow‐up in a cancer survivor program.

Anti-Mullerian hormone levels in American girls by age and race/ethnicity.

Abstract Background: Anti-Mullerian Hormone (AMH), a proposed indicator of ovarian follicle reserve in adults, has not been characterized in pediatric and adolescent females by race and/or ethnicity. Objectives: To describe AMH levels in healthy American girls and determine the influence of age and race/ethnicity on AMH. Subjects: Subjects aged 10–21 years were recruited from primary care settings and emergency departments. Race/ethnicity was characterized as White, Black or Hispanic. Methods: Serum for AMH levels (ng/mL) was measured using an enzyme-linked immunosorbent assay. Results: Thirty-one White, 60 Black and 24 Hispanic subjects were recruited. Mean AMH levels were 3.19 ng/mL (22.8 pmol/L) (SD 2.12) for Whites, 3.25 ng/mL (23.2 pmol/L) (SD 2.23) for Blacks and 2.97 ng/mL (21.2 pmol/L) (SD 1.75) for Hispanics. ANCOVA showed no difference in AMH levels among race/ethnicities, controlling for age (p=0.91). Age was significantly associated with AMH (p<0.001, R2=0.12). Conclusion: AMH levels do not vary by race/ethnicity, and AMH levels increase with age.

Perceptions of body mass index (BMI) in pediatric cancer survivors and their providers

Abnormalities in BMI are well documented in childhood cancer survivors. Perceptions of BMI status in cancer survivors have been understudied. This study determines the accuracy of parent/survivor and provider reporting of BMI status in a cancer survivor program.

Endocrine Late Effects in Childhood Cancer Survivors

Endocrine complications are highly prevalent in childhood cancer survivors. Approximately 50% of survivors will experience at least one hormonal disorder over the course of their lives. Endocrine complications often are observed in survivors previously treated with radiation to the head, neck, or pelvis. We provide an overview the most common endocrine late effects seen in survivors, including hypothalamic-pituitary dysfunction, primary thyroid dysfunction, obesity, diabetes mellitus, metabolic syndrome, and decreased bone mineral density. Primary gonadal injury is discussed elsewhere in this series. Given a variable latency interval, a systematic approach where individuals are periodically screened on the basis of their risk factors can help to improve health outcomes by prompt diagnosis and treatment of evolving endocrinopathies. These recommendations must be revised in the future given changes and improvements in cancer treatment over time.