Age stratifies disease extent in pediatric and young adult fusion-positive papillary thyroid carcinoma.
In a retrospective international cohort of fusion-positive papillary thyroid carcinoma in patients aged 0–25 years, age 0–14 years was associated with higher odds of baseline N1b and/or M1 disease, while advanced presentation did not significantly differ between RET- and NTRK-fusion groups.
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In a retrospective international cohort of fusion-positive papillary thyroid carcinoma in patients aged 0–25 years, age 0–14 years was associated with higher odds of baseline N1b and/or M1 disease, while advanced presentation did not significantly differ between RET- and NTRK-fusion groups.
Research significance
The evidence supports younger age as a potential clinical risk-stratification marker within fusion-positive pediatric and young adult PTC; it may justify testing age-informed staging and surveillance strategies, but the record does not show that this approach improves treatment selection or outcomes.
Source abstract
CONTEXT: Fusion-positive pediatric papillary thyroid carcinoma (PTC) often presents with regional nodal or distant disease, but factors explaining heterogeneity within fusion-positive tumors are incompletely defined. OBJECTIVE: To determine whether age, fusion group, or sex is associated with baseline N1b and/or M1 disease in fusion-positive pediatric and young adult PTC. DESIGN: Retrospective analysis of the international PEDIMAP cohort. SETTING: Multi-institutional pediatric and young adult thyroid carcinoma cohort. PATIENTS: Patients aged 0-25 years with PTC, documented somatic kinase fusion, and available fusion-partner information. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Advanced baseline presentation, defined as AJCC N1b and/or M1 disease. Associations were tested using Firth penalized logistic regression. RESULTS: Of 101 kinase fusion-positive PTCs identified among 646 PTCs, 2 rearranged during transfection (RET)-fusion cases were excluded because fusion-partner information was unavailable, yielding 99 fusion-positive tumors with known fusion partners: RET, n = 52; neurotrophic receptor tyrosine kinase (NTRK), n = 28; and other non-RET/NTRK kinase fusions, n = 19. Among 95 patients with evaluable N- and M-stage, 64 (67.4%) had N1b and/or M1 disease. Age 0-14 years was associated with higher odds of advanced presentation than age 15-25 years (adjusted OR, 4.67; 95% CI, 1.84-12.75; P = .001). No significant difference in advanced presentation was found between NTRK and RET fusions (adjusted OR, 0.83; 95% CI, 0.29-2.50; P = .739). CONCLUSION: Within fusion-positive pediatric and young adult PTC, younger age was associated with greater baseline disease extent, whereas no significant difference in N1b/M1 presentation was found between RET and NTRK-fusion groups. These findings support careful baseline assessment of regional and distant disease in younger fusion-positive patients.