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Published on: June 9, 2023
The landscape of pediatric differentiated thyroid carcinoma and predictors of invasive disease: a CATC study
Jonathan D Wasserman1, Amber R Isaza2, Steven G Waguespack3
1Division of Endocrinology, Department of Pediatrics, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
Insights
Pediatric differentiated thyroid carcinoma (DTC) is often invasive in younger males and those with specific tumor mutations. Less aggressive treatments have not worsened outcomes for children with DTC.
Area of Science:
- Pediatric Oncology
- Endocrinology
- Cancer Genomics
Background:
- Differentiated thyroid carcinoma (DTC) is a rare pediatric cancer (2-4% of childhood cancers).
- Limited data exists on pediatric DTC patient and tumor characteristics due to low institutional case volumes.
- The Child and Adolescent Thyroid Consortium (CATC) was formed to address these data limitations.
Purpose of the Study:
- To analyze the landscape of pediatric DTC.
- To identify predictors of invasive disease in pediatric DTC patients.
Main Methods:
- International, multicenter retrospective analysis of pediatric DTC (age <19) diagnosed between 2010-2019.
- Data collected from five high-volume pediatric centers.
- Analysis included patient demographics, tumor characteristics, and treatment outcomes.
Main Results:
- The cohort comprised 715 children (78.3% female) with a median age of 15.2 years.
- Papillary thyroid carcinoma (PTC) accounted for 94% of cases; follicular thyroid carcinoma (FTC) for 6%.
- Males and children under 10 years old showed more advanced disease stages (T, N, M). Extrathyroidal extension (ETE) correlated with nodal and pulmonary metastases. Oncogenic fusions were linked to more advanced N and M stages compared to BRAFV600E mutations.
Conclusions:
- Invasive pediatric DTC is associated with younger age (<10 years), male sex, oncogenic fusions, and ETE.
- Therapeutic deintensification since 2015 has not negatively impacted disease outcomes.
- Identifying these associations can aid in pediatric DTC care and prognostication.
Context:
Differentiated thyroid carcinoma (DTC) is rare in children, comprising 2% to 4% of pediatric cancers. Because of low case volumes at individual institutions, comprehensive data on patient and tumor characteristics and treatment outcomes are limited. The Child and Adolescent Thyroid Consortium was established in 2019 to address this gap and to assess impact of changes in practice on outcomes.
Objective:
This inaugural Child and Adolescent Thyroid Consortium study analyzes the landscape of pediatric DTC and predictors of invasive disease.
Design:
International, multicenter retrospective analysis of children (
Setting:
Five high-volume pediatric centers.
Results:
The cohort included 715 children (78.3% female) diagnosed with DTC at median age 15.2 years (range: 3.2-18.9). There were 673 (94%) patients with papillary thyroid carcinoma (PTC) and 42 (6%) had follicular thyroid carcinoma. Among patients with PTC, stage 1(M0) disease was present in 562 individuals (83.5%; 222 N0, 161 N1a, and 179 N1b). Stage 2 (M1) disease was present in 111 (16.5%) children with PTC and 1/42 (2.4%) with follicular thyroid carcinoma. Males and children aged <10 years exhibited more advanced T, N, and M stages. Any extrathyroidal extension correlated with increased nodal and pulmonary metastases. Oncogenic fusions, compared with BRAFV600E, were associated with more advanced N and M stages. Deintensification of therapy since 2015 was not associated with changes in disease outcomes.
Conclusion:
Invasive DTC is associated with age <10 years, male sex, tumors driven by oncogenic fusions, and extrathyroidal extension. Despite less aggressive therapies in recent years, disease outcomes have not worsened. Recognition of these associations may guide care and prognostication.
