Research Article

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

  1. Eric J. Chow MD, MPH1,2,*,
  2. Debra L. Friedman MD, MS3,
  3. Marilyn Stovall PhD4,
  4. Yutaka Yasui PhD5,
  5. John A. Whitton MS2,
  6. Leslie L. Robison PhD6,
  7. Charles A. Sklar MD7

Article first published online: 20 MAY 2009

DOI: 10.1002/pbc.22082

Issue

Pediatric Blood & Cancer

Pediatric Blood & Cancer

Volume 53, Issue 3, pages 432–437, September 2009

Additional Information

How to Cite

Chow, E. J., Friedman, D. L., Stovall, M., Yasui, Y., Whitton, J. A., Robison, L. L. and Sklar, C. A. (2009), Risk of thyroid dysfunction and subsequent thyroid cancer among survivors of acute lymphoblastic leukemia: A report from the Childhood Cancer Survivor Study. Pediatric Blood & Cancer, 53: 432–437. doi: 10.1002/pbc.22082

Author Information

  1. 1

    Department of Pediatrics, University of Washington, Seattle, Washington

  2. 2

    Fred Hutchinson Cancer Research Center, Seattle, Washington

  3. 3

    Division of Cancer Control and Prevention, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee

  4. 4

    Department of Radiation Physics, University of Texas, M.D. Anderson Cancer Center, Houston, Texas

  5. 5

    Department of Public Health Sciences, University of Alberta, Edmonton, Alberta, Canada

  6. 6

    Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee

  7. 7

    Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York

*Fred Hutchinson Cancer Research Center, PO Box 19024, Mailstop M4-C308, Seattle, WA 98109-1024.

Publication History

  1. Issue published online: 13 JUL 2009
  2. Article first published online: 20 MAY 2009
  3. Manuscript Accepted: 2 APR 2009
  4. Manuscript Received: 3 FEB 2009

Funded by

  • National Institutes of Health. Grant Number: U24-CA55727

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Keywords:

  • hyperthyroidism;
  • hypothyroidism;
  • late effects;
  • leukemia;
  • radiation;
  • thyroid cancer

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. © 2009 Wiley-Liss, Inc.

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