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.