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Endocrine Abnormalities Increase Over Time in Aging Survivors of Childhood Cancer

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Key Points

  • The cumulative incidence of endocrinopathies increased steadily over time.
  • Risk was substantially increased among survivors with exposure to high-risk therapies.

The cumulative incidence of endocrinopathies steadily increased over time in aging survivors of childhood cancers, according to an analysis of data from the Childhood Cancer Survivor Study reported by Mostoufi-Moab et al in the Journal of Clinical Oncology.

Study Details

The study included self-reported conditions in 14,290 5-year survivors from the study, who had a median age of 6 years at diagnosis (range, < 1–20 years) and 32 years at last follow-up (range, = 5–58 years). The definition of high-risk therapeutic exposures was adapted from the Children’s Oncology Group Long-Term Follow-Up Guidelines. Risks of primary hypothyroidism, hyperthyroidism, thyroid neoplasms, hypopituitarism, obesity, diabetes, and gonadal dysfunction were compared between patients and siblings.

Risk Over Time

The cumulative incidence of endocrine abnormalities increased steadily across the lifespan of survivors (P < .01 for all), and survivors had an increased risk for all thyroid disorders and diabetes regardless of treatment exposure vs siblings (P < .001 for all).

Effect of High-Risk Exposures

For survivors with vs without exposure to high-risk therapies, risk was increased for primary hypothyroidism (hazard ratio [HR] = 6.6, 95% confidence interval [CI] = 5.6–7.8), hyperthyroidism (HR = 1.8, 95% CI = 1.2–2.8), thyroid nodules (HR = 6.3, 95% CI = 5.2–7.5), thyroid cancer (HR = 9.2, 95% CI = 6.2–13.7), growth hormone deficiency (HR = 5.3, 95% CI = 4.3–6.4), obesity (relative risk [RR] = 1.8, 95% CI = 1.7–2.0), and diabetes (RR = 1.9, 95% CI = 1.6–2.4). Women who had received high-risk therapies had a sixfold increased risk for premature ovarian insufficiency (P < .001). Men had a greater risk for testosterone replacement (P < .001) after a cyclophosphamide equivalent dose of ≥ 20 g/m2 or testicular irradiation at ≥ 20 Gy.

The investigators concluded: “Endocrinopathies in survivors increased substantially over time, underscoring the need for lifelong subspecialty follow-up of those at risk.”

The study was supported by the National Cancer Institute and the American Lebanese Syrian Associated Charities for the St Jude Children’s Research Hospital.

Sogol Mostoufi-Moab, MD, MSCE, of The Children’s Hospital of Philadelphia, is the corresponding author of the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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