Risk of thyroid dysfunction and subsequent thyroid cancer among survivors of acute lymphoblastic leukemia: A report from the Childhood Cancer Survivor Study

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Abstract
Background To determine the risk of thyroid dysfunction and subsequent thyroid cancer among childhood acute lymphoblastic leukemia (ALL) survivors. Procedure Rates of self‐reported thyroid dysfunction and thyroid cancer were determined among 3,579 ALL survivors participating in the Childhood Cancer Survivor Study, a cohort of 5‐year survivors of pediatric cancers diagnosed from 1970 to 1986, and compared with 3,846 siblings and population rates, respectively. Results The cumulative incidence of hypo‐ and hyperthyroidism among survivors 15 years following leukemia diagnosis was 1.6% (95% CI 1.1, 2.1) and 0.6% (95% CI 0.3, 1.1), respectively, both significantly increased compared with siblings. In multivariate analysis, survivors who received ≥20 Gy cranial radiotherapy plus any spinal radiotherapy had the highest risk of subsequent hypothyroidism (HR 8.3, 95% CI 3.3, 20.5) compared with those treated with chemotherapy alone. Craniospinal radiotherapy also was associated with an increased risk of subsequent hyperthyroidism (HR 6.1, 95% CI 1.1, 34.2) compared with chemotherapy alone, as well as an increased risk of subsequent thyroid cancers (SIR 30.3, 95% CI 14.5, 55.7) compared with population rates. In radiation dosimetry analysis, pituitary doses ≥20 Gy combined with thyroid doses ≥10 Gy were associated with hypothyroidism, whereas pituitary doses ≥20 Gy combined with thyroid doses ≥15 Gy were associated with hyperthyroidism. Conclusions The risk of thyroid dysfunction and thyroid cancer was increased among childhood ALL survivors treated with craniospinal radiotherapy. In these individuals, long‐term surveillance is warranted as no obvious plateau in risk was seen, even after 25 years of follow‐up. Pediatr Blood Cancer 2009;53:432–437.
Funding Information
  • National Institutes of Health (U24-CA55727)