TY - JOUR
T1 - Primary Hypothyroidism in Childhood Cancer Survivors Treated With Radiation Therapy
T2 - A PENTEC Comprehensive Review
AU - Milano, Michael T
AU - Vargo, John A
AU - Yorke, Ellen D
AU - Ronckers, Cécile M
AU - Kremer, Leontien C
AU - Chafe, Susan M J
AU - van Santen, Hanneke M
AU - Marks, Lawrence B
AU - Bentzen, Søren M
AU - Constine, Louis S
AU - Vogelius, Ivan R
N1 - Copyright © 2021 Elsevier Inc. All rights reserved.
PY - 2024/6/1
Y1 - 2024/6/1
N2 - PURPOSE: From the Pediatric Normal Tissue Effects in the Clinic (PENTEC) initiative, a systematic review and meta-analysis of publications reporting on radiation dose-volume effects for risk of primary hypothyroidism after radiation therapy for pediatric malignancies was performed.METHODS AND MATERIALS: All studies included childhood cancer survivors, diagnosed at age <21 years, whose radiation therapy fields exposed the thyroid gland and who were followed for primary hypothyroidism. Children who received pituitary-hypothalamic or total-body irradiation were excluded. PubMed and the Cochrane Library were searched for studies published from 1970 to 2017. Data on age at treatment, patient sex, radiation dose to neck or thyroid gland, specific endpoints for hypothyroidism that were used in the studies, and reported risks of hypothyroidism were collected. Radiation dose-volume effects were modeled using logistic dose response. Relative excess risk of hypothyroidism as a function of age at treatment and sex was assessed by meta-analysis of reported relative risks (RR) and odds ratios.RESULTS: Fifteen publications (of 1709 identified) were included for systematic review. Eight studies reported data amenable for dose-response analysis. At mean thyroid doses of 10, 20, and 30 Gy, predicted rates of uncompensated (clinical) hypothyroidism were 4%, 7%, and 13%, respectively. Predicted rates of compensated (subclinical) hypothyroidism were 12%, 25%, and 44% after thyroid doses of 10, 20, and 30 Gy, respectively. Female sex (RR = 1.7, P < .0001) and age >15 years at radiation therapy (RR = 1.3, P = .005) were associated with higher risks of hypothyroidism. After a mean thyroid dose of 20 Gy, predicted risks of hypothyroidism were 13% for males <14 years of age, increasing to 29% for females >15 years of age.CONCLUSION: A radiation dose response for risk of hypothyroidism is evident; a threshold radiation dose associated with no risk is not observed. Thyroid dose exposure should be minimized when feasible. Data on hypothyroidism after radiation therapy should be better reported to facilitate pooled analyses.
AB - PURPOSE: From the Pediatric Normal Tissue Effects in the Clinic (PENTEC) initiative, a systematic review and meta-analysis of publications reporting on radiation dose-volume effects for risk of primary hypothyroidism after radiation therapy for pediatric malignancies was performed.METHODS AND MATERIALS: All studies included childhood cancer survivors, diagnosed at age <21 years, whose radiation therapy fields exposed the thyroid gland and who were followed for primary hypothyroidism. Children who received pituitary-hypothalamic or total-body irradiation were excluded. PubMed and the Cochrane Library were searched for studies published from 1970 to 2017. Data on age at treatment, patient sex, radiation dose to neck or thyroid gland, specific endpoints for hypothyroidism that were used in the studies, and reported risks of hypothyroidism were collected. Radiation dose-volume effects were modeled using logistic dose response. Relative excess risk of hypothyroidism as a function of age at treatment and sex was assessed by meta-analysis of reported relative risks (RR) and odds ratios.RESULTS: Fifteen publications (of 1709 identified) were included for systematic review. Eight studies reported data amenable for dose-response analysis. At mean thyroid doses of 10, 20, and 30 Gy, predicted rates of uncompensated (clinical) hypothyroidism were 4%, 7%, and 13%, respectively. Predicted rates of compensated (subclinical) hypothyroidism were 12%, 25%, and 44% after thyroid doses of 10, 20, and 30 Gy, respectively. Female sex (RR = 1.7, P < .0001) and age >15 years at radiation therapy (RR = 1.3, P = .005) were associated with higher risks of hypothyroidism. After a mean thyroid dose of 20 Gy, predicted risks of hypothyroidism were 13% for males <14 years of age, increasing to 29% for females >15 years of age.CONCLUSION: A radiation dose response for risk of hypothyroidism is evident; a threshold radiation dose associated with no risk is not observed. Thyroid dose exposure should be minimized when feasible. Data on hypothyroidism after radiation therapy should be better reported to facilitate pooled analyses.
KW - Adolescent
KW - Age Factors
KW - Cancer Survivors/statistics & numerical data
KW - Child
KW - Child, Preschool
KW - Dose-Response Relationship, Radiation
KW - Female
KW - Humans
KW - Hypothyroidism/etiology
KW - Infant
KW - Male
KW - Neoplasms/radiotherapy
KW - Organs at Risk/radiation effects
KW - Radiation Injuries/etiology
KW - Radiotherapy Dosage
KW - Sex Factors
KW - Thyroid Gland/radiation effects
KW - Young Adult
UR - http://www.scopus.com/inward/record.url?scp=85192654794&partnerID=8YFLogxK
U2 - 10.1016/j.ijrobp.2021.02.001
DO - 10.1016/j.ijrobp.2021.02.001
M3 - Review
C2 - 33810948
SN - 0360-3016
VL - 119
SP - 482
EP - 493
JO - International journal of radiation oncology, biology, physics
JF - International journal of radiation oncology, biology, physics
IS - 2
ER -