Age, American Thyroid Association Risk Group, and Response to Therapy Are Prognostic Factors in Children With Differentiated Thyroid Cancer

Abstract

Context Against the background of increasing incidence, pediatric differentiated thyroid carcinoma (DTC) frequently presents with advanced disease and high recurrence rates while prognosis remains excellent. Background We investigated the use of a pediatric classification and an adult response to therapy risk stratification for pediatric DTC patients and their implications for adaptation of treatment and follow-up. Methods Data from patients aged <18 years with a diagnosis of primary DTC, registered with the German Pediatric Oncology Hematology-Malignant Endocrine Tumor registry since 1995, were analyzed. For risk prediction, patients were retrospectively assigned to the American Thyroid Association (ATA) risk groups and evaluated for response to therapy. Results By October 2019, 354 patients with DTC had been reported (median age at diagnosis 13.7 years, range 3.6-17.9) with lymph node and distant metastases in 74.3% and 24.5%. Mean follow-up was 4.1 years (range 0-20.6). Ten-year overall and event-free survival (EFS) rates were 98.9% and 78.1%. EFS was impaired for patients with lymph node and distant metastases (P < .001), positive postoperative thyroglobulin (P = .006), incomplete resection (P = .002), sequential surgeries to achieve total thyroidectomy (P = .042), invasion of capsule (P < .001) and lymph vessels (P = .005), infiltration of surrounding soft tissues (P < .001), tumor multifocality (P < .001), ATA intermediate- and high-risk group (P < .001), and age <10 years (P < .001). Multivariate analysis revealed age <10 years at diagnosis, ATA high-risk level, and poor response to therapy as significant negative prognostic factors for EFS. Conclusion Age, ATA risk group, and response to therapy emerged as significant prognostic factors for EFS in pediatric patients with DTC, requiring risk-adapted individualized therapy and follow-up.

Tumor size is an independent negative prognostic factor for event free survival in children with differentiated thyroid cancer

“…This is consistent with several previous studies (8,12,(22)(23)(24)(25). Despite the presence of advanced disease in children with DTC in this cohort, long-term prognosis was excellent and 10 years overall survival was 98.4%, which is also in line with previous reports on pediatric DTC from different ethnicities (8,13,24,26,27). To further determine potential independent factors for patients' outcome, we included the clinico-pathological factors in multivariate Cox regression analysis.…”

“…There are several reports where large tumor size and initial distant metastasis are found to have adverse impact on the recurrence and prognosis of pediatric DTC (14,24,28,29). Although several other factors have been previously reported to be negatively associated with EFS, such as age, extent of resection and serum thyroglobulin levels (8,25,30), in our study, age, ATA risk stratification and other clinicopathological parameters (extrathyroidal extension, bilaterality, multifocality, lymphovascular invasion and response to therapy) were not independent risk factors for EFS.…”

“…Pediatric DTC differ clinically from adult DTC. At diagnosis children usually present with more advanced disease, with larger tumor size, frequent extrathyroidal extension (ETE), and high rate of lymph node metastasis and distant metastasis (7)(8)(9). Molecular differences between pediatric and adult DTC have also been established.…”

“…In 2015, the American Thyroid Association (ATA) published management guidelines for children with DTC, where these guidelines classify patient into low, intermediate and high risk categories ( 14 ). Recent studies have illustrated that ATA risk group is a prognostic factor for event-free survival (EFS) in pediatric DTC patients ( 8 , 15 , 16 ).…”

Prognostic factors in children and adolescents with differentiated thyroid carcinoma treated with total thyroidectomy and RAI: a real-life multicentric study

“…Indeed, our findings are in partial agreement with these papers [ 17 , 20 ]. In a recent paper [ 29 ], response to therapy together with age and ATA risk predicted significantly event-free survival.…”