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

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 >or=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 >or=20 Gy combined with thyroid doses >or=10 Gy were associated with hypothyroidism, whereas pituitary doses >or=20 Gy combined with thyroid doses >or=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.

FIGURE 1

Cumulative incidence of hypothyroidism among 5-year acute lymphoblastic leukemia (ALL) survivors versus siblings, stratified by sex. Outcomes censored by alternative thyroid conditions, leukemia recurrence, second malignancy, hematopoietic cell transplant, and death. * Log rank test, p<0.05 when survivors compared with same-sex siblings; ^ log rank test, p<0.05 when females compared with males, restricted to either survivors or siblings.

FIGURE 2

Cumulative incidence of hyperthyroidism among 5-year acute lymphoblastic leukemia (ALL) survivors versus siblings, stratified by sex. Outcomes censored by alternative thyroid conditions, leukemia recurrence, second malignancy, hematopoietic cell transplant, and death. * Log rank test, p<0.05 when survivors compared with same-sex siblings; no differences when females compared with males, restricted to either survivors or siblings.