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Clinical and Pathological Factors Associated with Disease Persistence in Pediatric Patients with Differentiated
Simone De Leo1, Valeria Bottici2, Gabriella Pellegriti3,4
1Endocrine Oncology Unit, Department of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS, Milan, Italy.
Insights
Persistent differentiated thyroid carcinoma (DTC) in children is linked to gross extrathyroidal extension and lymph node uptake on whole-body scans after initial radioactive iodine treatment. These factors aid in risk stratification for tailored pediatric DTC management.
Area of Science:
- Pediatric Oncology
- Endocrinology
- Nuclear Medicine
Background:
- Pediatric differentiated thyroid carcinoma (DTC) presents unique clinical, pathological, and molecular features distinct from adult cases.
- Effective management strategies require understanding factors influencing treatment outcomes in young patients.
- Previous studies often lack large cohorts and long-term follow-up for pediatric DTC.
Purpose of the Study:
- To evaluate the outcomes of pediatric DTC patients.
- To identify clinical and pathological factors associated with persistent disease in this population.
- To inform risk stratification and personalize treatment approaches for pediatric DTC.
Main Methods:
- A multicenter retrospective cohort study included 538 pediatric patients (≤18 years) diagnosed with DTC since 2000.
- Evaluated both biochemical (BIR) and structural (SIR) incomplete responses.
- Analyzed factors associated with persistent disease using multivariable analysis, including gross extrathyroidal extension (ETE) and lymph node uptake on whole-body scan (WBS) after radioactive iodine treatment (RAIT).
Main Results:
- Of 538 patients, 77% had no evidence of disease after a median follow-up of 85 months; 23% had persistent disease (12.6% BIR, 10.4% SIR).
- Gross ETE and lymph node uptake on WBS after the first RAIT were significantly associated with overall persistent disease (BIR or SIR).
- T4 tumor stage and lymph node uptake on WBS after the first RAIT were independently associated with structural incomplete response (SIR).
Conclusions:
- This large cohort study with extended follow-up provides critical insights into pediatric DTC.
- Gross ETE, T4 tumor stage, and lymph node uptake on WBS after initial RAIT are key independent predictors of persistent disease.
- These findings underscore the necessity of precise risk stratification for optimizing individualized treatment strategies in pediatric DTC.
Abstract:
Background: 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. Methods: 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. Results: 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, p = 0.0015) and lymph node uptake at whole-body scan (WBS) after the first RAIT (OR 3.31, CI 1.77-6.19, p = 0.0002). Multivariable analysis showed that the features significantly associated with SIR were T4 tumor (OR 4.3, CI 1.38-13.44, p = 0.01) and lymph node uptake at WBS after the first RAIT (OR 3.39, CI 1.5-7.67, p = 0.003). Conclusions: 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.
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