Endocrine Abnormalities in Aging Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study

• Authors: Sogol Mostoufi-Moab, University of Pennsylvania; Kristy Seidel, Fred Hutchinson Cancer Research Center; Wendy M. Leisenring, Fred Hutchinson Cancer Research Center; Gregory T. Armstrong, St Jude Children’s Research Hospital; Kevin C. Oeffinger, Memorial Sloan Kettering Cancer Center; Marilyn Stovall, University of Texas; Lillian Meacham, Emory University; Daniel M. Green, St Jude Children’s Research Hospital; Rita Weathers, University of Texas; Jill P. Ginsberg, University of Pennsylvania; Leslie L. Robison, St Jude Children’s Research Hospital; Charles A. Sklar, Memorial Sloan Kettering Cancer Center
• Journal Title: Journal of Clinical Oncology
• Volume: Volume 34, Number 27
• Publisher: American Society of Clinical Oncology | 2016-09-20, Pages 3240-+
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1200/JCO.2016.66.6545
• Subjects: Health Sciences, Oncology; Health Sciences, Public Health
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; FOLLOW-UP GUIDELINES; ADULT SURVIVORS; HEALTH CONDITIONS; COHORT; RISK; OUTCOMES; CARE

Abstract

Purpose: The development of endocrinopathies in survivors of childhood cancer as they age remains understudied. We characterized endocrine outcomes in aging survivors from the Childhood Cancer Survivor Study on the basis of therapeutic exposures. Patients and Methods: We analyzed self-reported conditions in 14,290 5-year survivors from the Childhood Cancer Survivor Study, with a median age 6 years (range, < 1 to 20 years) at diagnosis and 32 years (range, 5 to 58 years) at last follow-up. Identification of high-risk therapeutic exposures was adopted from the Children's Oncology Group Long-Term Follow-Up Guidelines. Cumulative incidence curves and prevalence estimates quantified and regression models compared risks of primary hypothyroidism, hyperthyroidism, thyroid neoplasms, hypopituitarism, obesity, diabetes mellitus, or gonadal dysfunction between survivors and siblings. Results: The cumulative incidence and prevalence of endocrine abnormalities increased across the lifespan of survivors (P < .01 for all). Risk was significantly higher in survivors exposed to high-risk therapies compared with survivors not so exposed for primary hypothyroidism (hazard ratio [HR], 6.6; 95% CI, 5.6 to 7.8), hyperthyroidism (HR, 1.8; 95% CI, 1.2 to 2.8), thyroid nodules (HR, 6.3; 95% CI, 5.2 to 7.5), thyroid cancer (HR, 9.2; 95% CI, 6.2 to 13.7), growth hormone deficiency (HR, 5.3; 95% CI, 4.3 to 6.4), obesity (relative risk, 1.8; 95% CI, 1.7 to 2.0), and diabetes mellitus (relative risk, 1.9; 95% CI, 1.6 to 2.4). Women exposed to high-risk therapies had six-fold increased risk for premature ovarian insufficiency (P < .001), and men demonstrated higher prevalence of testosterone replacement (P < .001) after cyclophosphamide equivalent dose of 20 g/m2 or greater or testicular irradiation with 20 Gy or greater. Survivors demonstrated an increased risk for all thyroid disorders and diabetes mellitus regardless of treatment exposures compared with siblings (P < .001 for all). Conclusion: Endocrinopathies in survivors increased substantially over time, underscoring the need for lifelong subspecialty follow-up of those at risk.