Association Between Radioactive Iodine Treatment for Pediatric and Young Adulthood Differentiated Thyroid Cancer and Risk of Second Primary Malignancies.

Elisa Pasqual,Choonsik Lee,Cari M Kitahara,Sara Schonfeld,Amy Berrington De Gonzalez,Lindsay M Morton,Daphnée Villoing

doi:10.1200/jco.21.01841

Abstract

PURPOSESince the 1980s, both the incidence of differentiated thyroid cancer (DTC) and use of radioactive iodine (RAI) treatment increased markedly. RAI has been associated with an increased risk of leukemia, but risks of second solid malignancies remain unclear. We aimed to quantify risks of second malignancies associated with RAI treatment for DTC in children and young adults, who are more susceptible than older adults to the late effects of radiation.METHODSUsing nine US SEER cancer registries (1975-2017), we estimated relative risks (RRs) for solid and hematologic malignancies associated with RAI (yes v no or unknown) using Poisson regression among ≥ 5- and ≥ 2-year survivors of nonmetastatic DTC diagnosed before age 45 years, respectively.RESULTSAmong 27,050 ≥ 5-year survivors (median follow-up = 15 years), RAI treatment (45%) was associated with increased risk of solid malignancies (RR = 1.23; 95% CI, 1.11 to 1.37). Risks were increased for uterine cancer (RR = 1.55; 95% CI, 1.03 to 2.32) and nonsignificantly for cancers of the salivary gland (RR = 2.15; 95% CI, 0.91 to 5.08), stomach (RR = 1.61; 95% CI, 0.70 to 3.69), lung (RR = 1.42; 95% CI, 0.97 to 2.08), and female breast (RR = 1.18; 95% CI, 0.99 to 1.40). Risks of total solid and female breast cancer, the most common cancer type, were highest among ≥ 20-year DTC survivors (RRsolid = 1.47; 95% CI, 1.24 to 1.74; RRbreast = 1.46; 95% CI, 1.10 to 1.95). Among 32,171 ≥ 2-year survivors, RAI was associated with increased risk of hematologic malignancies (RR = 1.51; 95% CI, 1.08 to 2.01), including leukemia (RR = 1.92; 95% CI, 1.04 to 3.56). We estimated that 6% of solid and 14% of hematologic malignancies in pediatric and young adult DTC survivors may be attributable to RAI.CONCLUSIONIn addition to leukemia, RAI treatment for childhood and young-adulthood DTC was associated with increased risks of several solid cancers, particularly more than 20 years after exposure, supporting the need for long-term surveillance of these patients.

Highlights

The incidence of differentiated thyroid cancer (DTC) increased by an average of 3.6% per year between the mid-1970s and mid-2010s in the United States.[1,2] With 15,445 estimated new cases in 2020, thyroid cancer ranks as the second most common cancer in people younger than age 45 years in the United States.[3]
Among 32,171 $ 2-year survivors, radioactive iodine (RAI) was associated with increased risk of hematologic malignancies (RR 5 1.51; 95% CI, 1.08 to 2.01), including leukemia (RR 5 1.92; 95% CI, 1.04 to 3.56)
We estimated that 6% of solid and 14% of hematologic malignancies in pediatric and young adult DTC survivors may be attributable to RAI

Summary

Introduction

The incidence of differentiated thyroid cancer (DTC) increased by an average of 3.6% per year between the mid-1970s and mid-2010s (from 4.56 to 14.42 per 100,000 person-years) in the United States.[1,2] With 15,445 estimated new cases in 2020, thyroid cancer ranks as the second most common cancer in people younger than age 45 years in the United States.[3] Use of radioactive iodine (RAI) for DTC treatment increased through 2009, especially in young patients.[4,5,6,7,8,9] in addition to providing limited to no survival benefit for localized DTC, RAI is associated with increased risks of short-term and long-term adverse outcomes,[10,11,12,13,14] including secondary primary malignancies (SPMs), such as leukemia.[15,16,17,18,19,20,21,22] In response to this evidence, the 2009 and 2015 American Thyroid Association guidelines committee issued recommendations against RAI therapy for low-risk DTCs , 1 cm and in support of lower levels of RAI administered activity for larger tumors.[23,24] A similar approach was suggested in the pediatric guidelines, without explicit discouragement of RAI treatment for low-risk DTCs, and the subject remains controversial.[25,26,27]

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