Radioactive Iodine-Refractory Pulmonary Metastases of Papillary Thyroid Cancer in Children, Adolescents, and Young Adults.

[CONTEXT] Few studies have explored radioactive iodine-refractory (RAIR) disease in children, adolescents, and young adults with papillary thyroid cancer (CAYA-PTC).

[OBJECTIVE] This study systematically investigated the clinicopathologic characteristics and prognosis of CAYA-PTC with RAIR disease.

[METHODS] Sixty-five patients with PTC aged ≤20 years were enrolled in this study, and all patients were confirmed to have pulmonary metastases. Clinicopathologic profiles were compared between the radioactive iodine-avid (RAIA) and RAIR groups. Univariate and multivariate regression analyses were performed to identify risk factors for RAIR status and progressive disease (PD). Gene alterations were detected in 17 patients.

[RESULTS] Overall, 20 patients were included in the RAIR group, accounting for 30.8% (20/65) of all patients. No significant difference in pathologic characteristics was observed between patients aged <15 years and patients aged 15-20 years, but younger patients were more likely to develop RAIR disease (hazard ratio [HR] 3.500, 95% CI 1.134-10.803, P = .023). RET fusions were the most common genetic alterations in CAYA-PTC, but an association with RAIR disease was not detected (P = .210). RAIR disease (HR 10.008, 95% CI 2.427-41.268, P = .001) was identified as an independent predictor of PD. The Kaplan-Meier curve revealed a lower progression-free survival (PFS) and disease-specific survival (DSS) rate in the RAIR group than in the RAIA group (P < .001 and P = .039). Likewise, RAIR disease was a risk factor for unfavorable PFS in patients aged <15 years (P < .001).

[CONCLUSION] RAIR disease occurs in one-third of CAYA-PTC with pulmonary metastases. Younger patients (aged < 15 years) are more susceptible to RAIR status, which leads to unfavorable PFS and DSS.