Clinical and Pathological Factors Associated with Disease Persistence in Pediatric Patients with Differentiated Thyroid Carcinoma

<b><i>Background:</i></b> Differentiated thyroid carcinoma (DTC) in pediatric patients has specific clinical, pathological, and molecular characteristics, making its management different from that of adults. Our study aimed to evaluate the outcome and factors associated with persistent disease in a large cohort of pediatric patients. <b><i>Methods:</i></b> We performed a multicenter retrospective cohort study, including patients aged ≤18 years, diagnosed with a DTC, since January 2000. Both biochemical (BIR) and structural (SIR) incomplete responses were evaluated. <b><i>Results:</i></b> We included 538 patients, 401/538 (74.5%) females, with a median age of 15 years (interquartile range [IQR] 13-17 years). Papillary thyroid cancer was the most prevalent histotype and 277/530 (52.3%) had lymph node metastases at diagnosis. Vascular invasion and gross extrathyroidal extension (ETE) were reported in 133/326 (40.8%) and 91/533 (17.1%) of patients, respectively. T4 tumors represented 5% of the entire cohort. Radioactive iodine treatment (RAIT) was administered to 493/533 (92.5%) patients, and among them 138/493 (28%) received more than one RAIT cycle. After a median follow-up of 85 months (IQR 42-126 months), 414/538 patients (77%) had no evidence of disease and 124/538 patients (23.0%) a disease persistence: BIR in 68/538 patients (12.6%) and SIR in 56/538 patients (10.4%). In a multivariable analysis, the features significantly associated with persistent disease (BIR or SIR) were gross ETE (odds ratio [OR] 2.81, confidence interval [CI] 1.49-5.32, <i>p</i> = 0.0015) and lymph node uptake at whole-body scan (WBS) after the first RAIT (OR 3.31, CI 1.77-6.19, <i>p</i> = 0.0002). Multivariable analysis showed that the features significantly associated with SIR were T4 tumor (OR 4.3, CI 1.38-13.44, <i>p</i> = 0.01) and lymph node uptake at WBS after the first RAIT (OR 3.39, CI 1.5-7.67, <i>p</i> = 0.003). <b><i>Conclusions:</i></b> Our study of a very large series of pediatric DTC with long follow-up provides valuable insights into the clinical and pathological features associated with disease persistence. We identified T4 tumor, lymph node uptake on WBS, and gross ETE as independent factors associated with persistent disease. These findings emphasize the importance of careful risk stratification in pediatric DTC, allowing for more individualized treatment approaches.