Childhood Cancer Survivors at Very High Risk of Later Endocrine Disorders in Scandinavian Study
In a population-based cohort study (Adult Life after Childhood Cancer in Scandinavia, or ALiCCS) reported in The Lancet, Licht et al assessed the lifetime risk of endocrine disorders in Scandinavian long-term survivors of childhood cancer. They found a nearly fivefold increased risk of hospital contact for endocrine disorders among survivors and a cumulative risk of endocrine disorders of > 40% by age 60 years in those diagnosed with cancer at ages 5 to 9 years.
Study Details
In the study, 31,723 ≥ 1-year survivors of cancer were identified from the national cancer registries of Denmark, Finland, Iceland, Norway, and Sweden, which have registration dating to the 1940s and 1950s. A comparison cohort of participants matched for age, sex, and country was randomly selected from national population registries. Study participants were linked to national hospital registries, and observed rates of first-time hospital contacts for endocrine disorders in childhood cancer survivors were compared with those derived from the population comparison cohort.
Increased Risk
Survivors were followed for a total of 418,528 person-years (median, 10 years; range, 0–42 years). Among survivors, 3,292 had hospital contact for an endocrine disorder compared with an expected 694 from the population comparison cohort, yielding a standardized hospitalization rate ratio (SHRR) of 4.8 (95% confidence interval [CI] = 4.6–5.0), including standard hospitalization rate ratios of 6.0 (95% CI = 5.6–6.4) for males and 4.0 (95% CI = 3.8–4.3) for females. The observed hospitalization rate was 787 per 100,000 person-years for survivors vs an expected rate of 166/100,000 person-years, yielding an absolute excess risk of 621/100,000 person-years.
Highest Risks
The highest risks for hospital contact were among patients with leukemia (SHRR = 7.3, 95% CI = 6.7–7.9), central nervous system tumors (SHRR = 6.6, 95% CI = 6.2–7.0), and Hodgkin lymphoma (SHRR = 6.2, 95% CI = 5.6–7.0); standard hospitalization rate ratios were 5.0 (95% CI = 4.1–6.0) for neuroblastoma, 4.0 (95% CI = 3.4–4.7) for non-Hodgkin lymphoma, and 1.8 (95% CI = 1.3–-2.5) for retinoblastoma.
Standard hospitalization rate ratios were highest in the first 2 decades of life (10.9 for ages 0–9 years and 10.7 for ages 10–19 years) and decreased thereafter. The absolute excess risk was approximately 1,000/100,000 person-years before 20 years of age and 400 per 100,000 person-years during the remaining lifetime.
Survivors with cancer diagnosed at ages 5 to 9 years had the highest cumulative risk of endocrine disorders, with 35% affected by age 40 years and 43% by age 60 years, reflecting a high rate of diagnosis of pituitary hypofunction.
Pituitary hypofunction (SHRR = 88.0), hypothyroidism (SHRR = 9.9), testicular dysfunction (SHRR = 42.5), and ovarian dysfunction (SHRR = 4.7) represented 61% of all excess disease-induced and treatment-induced endocrine disorders in survivors.
The investigators concluded: “A cumulative risk for endocrine disorders at 60 years of age of above 40% in survivors of childhood cancer emphasises the importance of minimisation of damaging treatment, intensification of secondary prevention, and targeting of survivor follow-up throughout life. Since most long-term childhood cancer survivors are not followed in a specialised late-effect clinic, they are a growing challenge for the primary care physician and medical specialists working outside the late-effect area.”
Sofie de Fine Licht, MSc, of the Danish Cancer Society Research Centre Survivorship Unit, Copenhagen, is the corresponding author for The Lancet article.
The study was funded by The Danish Council for Strategic Research. Dr. de Fine Licht has a minor stock ownership in Novo Nordisk.
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