{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:44:31Z","timestamp":1792640671062,"version":"4.5.0"},"reference-count":42,"publisher":"The Endocrine Society","license":[{"start":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:00:00Z","timestamp":1791590400000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81972496"],"award-info":[{"award-number":["81972496"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82473457"],"award-info":[{"award-number":["82473457"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Children and young adolescents with papillary thyroid cancer (CAYA-PTC) have high recurrence rates. Current guidelines advocate intensive treatment, yet existing risk stratification systems lack integration of genomic characteristics and provide limited precision in guiding surgical extent and postoperative radioactive iodine (RAI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>This retrospective, multicenter study analyzed 435 CAYA-PTC patients (ages 2-18 years) treated between 2006 and 2024. A clinicogenomic nomogram for disease-free survival (DFS) was developed using clinical data, postoperative pathology, and molecular testing of surgical tissue. Patients were stratified according to the nomogram score. Model performance was internally compared with the American Thyroid Association (ATA) pediatric risk system. Treatment associations were assessed by surgical extent (total thyroidectomy [TT] vs lobectomy) and receipt of postoperative RAI therapy within each risk stratification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Five variables were independent predictors of worse DFS: age \u226415 years, tumor size &amp;gt;4\u2005cm, lateral neck node involvement (N1b), coexisting Hashimoto thyroiditis, and RET\/NTRK fusions (all P &amp;lt; .05). The nomogram stratified patients into low-, intermediate-, and high-risk groups with 7-year DFS rates of 92.4%, 83.1%, and 56.4% (P &amp;lt; .001). In internal comparison, nomogram-based risk stratification had higher concordance index (0.721 vs 0.656) and 3-year AUC (0.748 vs 0.651) values than ATA stratification (both P &amp;lt; .05). TT was associated with better DFS in intermediate- and high-risk patients but not low-risk patients. Higher DFS with postoperative RAI was observed in the high-risk group (P = .028).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Using retrospective clinicogenomic features, our stratification suggests a risk-adapted framework for CAYA-PTC. However, nonsignificant differences, especially in small subgroups, do not establish treatment equivalence or confirm the safety of de-escalation. These findings represent associations that require future external validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgag418","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T11:48:43Z","timestamp":1791546523000},"source":"Crossref","is-referenced-by-count":1,"title":["Clinical and molecular genetic testing risk stratification for pediatric papillary thyroid carcinoma therapy"],"prefix":"10.1210","author":[{"given":"Lingyi","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Head and Neck Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital , Shanghai 200001 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital , Shanghai 200001 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zirui","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital , Shanghai 200001 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital , Shanghai 200001 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjia","family":"Fei","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital , Shanghai 200001 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anqi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital , Shanghai 200001 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunjun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center , Shanghai 200032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital , Shanghai 200001 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital , Shanghai 200001 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixian","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital , Shanghai 200001 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"He","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital , Shanghai 200001 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8121-5286","authenticated-orcid":false,"given":"Zhuoying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital , Shanghai 200001 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2026,10,10]]},"reference":[{"issue":"3","key":"2026102111431647500_dgag418-B1","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1007\/s00383-022-05069-3","article-title":"Incidence and prognosis of thyroid cancer in children: based on the SEER database","volume":"38","author":"Zhang","year":"2022","journal-title":"Pediatr Surg Int"},{"issue":"5","key":"2026102111431647500_dgag418-B2","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3892\/ijo.2021.5193","article-title":"New insights into the management of differentiated thyroid carcinoma in children and adolescents","volume":"58","author":"Zanella","year":"2021","journal-title":"Int J Oncol"},{"issue":"3","key":"2026102111431647500_dgag418-B3","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1210\/endrev\/bnaf003","article-title":"Molecular landscape and therapeutic strategies in pediatric differentiated thyroid carcinoma","volume":"46","author":"Yang","year":"2025","journal-title":"Endocr Rev"},{"issue":"10","key":"2026102111431647500_dgag418-B4","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1001\/jamapediatrics.2016.0486","article-title":"Thyroid disorders in children and adolescents: a review","volume":"170","author":"Hanley","year":"2016","journal-title":"JAMA Pediatr"},{"issue":"22","key":"2026102111431647500_dgag418-B5","doi-asserted-by":"crossref","first-page":"5625","DOI":"10.1158\/0008-5472.CAN-21-0761","article-title":"Diverse oncogenic fusions and distinct gene expression patterns define the genomic landscape of pediatric papillary thyroid carcinoma","volume":"81","author":"Stosic","year":"2021","journal-title":"Cancer Res"},{"key":"2026102111431647500_dgag418-B6","doi-asserted-by":"crossref","DOI":"10.4061\/2011\/845362","article-title":"Thyroid carcinoma in children and adolescents: systematic review of the literature","volume":"2011","author":"Vaisman","year":"2011","journal-title":"J Thyroid Res"},{"issue":"1","key":"2026102111431647500_dgag418-B7","article-title":"Clinical characteristics and prognosis of histological subtypes of papillary thyroid carcinoma in pediatric patients","volume":"5","author":"Akaishi","year":"2025","journal-title":"Endocr Oncol"},{"issue":"7","key":"2026102111431647500_dgag418-B8","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1089\/thy.2014.0460","article-title":"Management guidelines for children with thyroid nodules and differentiated thyroid cancer","volume":"25","author":"Francis","year":"2015","journal-title":"Thyroid"},{"issue":"10","key":"2026102111431647500_dgag418-B9","doi-asserted-by":"crossref","DOI":"10.1016\/j.jpedsurg.2025.162485","article-title":"Management of hypoparathyroidism after total thyroidectomy for differentiated thyroid cancer in children and young adolescents: experiences from a multicenter cohort in China","volume":"60","author":"Shi","year":"2025","journal-title":"J Pediatr Surg"},{"issue":"11","key":"2026102111431647500_dgag418-B10","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1016\/j.ejso.2019.08.016","article-title":"Pediatric thyroid cancer: a surgical challenge","volume":"45","author":"Shaha","year":"2019","journal-title":"Eur J Surg Oncol"},{"issue":"4","key":"2026102111431647500_dgag418-B11","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1089\/thy.2019.0231","article-title":"Risk stratification of pediatric patients with differentiated thyroid cancer: is total thyroidectomy necessary for patients at any risk?","volume":"30","author":"Sugino","year":"2020","journal-title":"Thyroid"},{"issue":"1","key":"2026102111431647500_dgag418-B12","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.jamcollsurg.2021.03.025","article-title":"Total thyroidectomy vs thyroid lobectomy for localized papillary thyroid cancer in children: a propensity-matched survival analysis","volume":"233","author":"Memeh","year":"2021","journal-title":"J Am Coll Surg"},{"issue":"13","key":"2026102111431647500_dgag418-B13","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1200\/JCO.21.01841","article-title":"Association between radioactive iodine treatment for pediatric and young adulthood differentiated thyroid cancer and risk of second primary malignancies","volume":"40","author":"Pasqual","year":"2022","journal-title":"J Clin Oncol"},{"issue":"18","key":"2026102111431647500_dgag418-B14","doi-asserted-by":"crossref","DOI":"10.1172\/JCI144847","article-title":"NTRK and RET fusion-directed therapy in pediatric thyroid cancer yields a tumor response and radioiodine uptake","volume":"131","author":"Lee","year":"2021","journal-title":"J Clin Invest"},{"issue":"4","key":"2026102111431647500_dgag418-B15","doi-asserted-by":"crossref","first-page":"e173","DOI":"10.1016\/S1470-2045(14)71116-7","article-title":"Nomograms in oncology: more than meets the eye","volume":"16","author":"Balachandran","year":"2015","journal-title":"Lancet Oncol"},{"key":"2026102111431647500_dgag418-B16","doi-asserted-by":"crossref","unstructured":"Yang L, Qian K, Huang Z, et al \u00a02026. Supplemental data from: Clinical and Molecular Genetic Testing Risk Stratification for Pediatric Papillary Thyroid Carcinoma Therapy. Zenodo. 10.5281\/zenodo.23040239","DOI":"10.1210\/clinem\/dgag418"},{"issue":"8","key":"2026102111431647500_dgag418-B17","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1210\/clinem\/dgaf090","article-title":"Approach to the pediatric patient with thyroid nodules","volume":"110","author":"Lai","year":"2025","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"2026102111431647500_dgag418-B18","doi-asserted-by":"crossref","DOI":"10.1016\/j.beem.2022.101715","article-title":"Pediatric thyroid cancer: recent developments","volume":"37","author":"Cherella","year":"2023","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"issue":"2","key":"2026102111431647500_dgag418-B19","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1089\/thy.2021.0255","article-title":"Cutoff age between pediatric and adult thyroid differentiated cancer: is 18 years old appropriate?","volume":"32","author":"Sugino","year":"2022","journal-title":"Thyroid"},{"issue":"19","key":"2026102111431647500_dgag418-B20","doi-asserted-by":"crossref","first-page":"2281","DOI":"10.1097\/CM9.0000000000000910","article-title":"Prognostic analysis of recurrence in children and adolescents with differentiated thyroid cancer","volume":"133","author":"Wang","year":"2020","journal-title":"Chin Med J (Engl)"},{"issue":"6","key":"2026102111431647500_dgag418-B21","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.3390\/diagnostics13061187","article-title":"The prognostic significance of BRAF gene analysis in children and adolescents with papillary thyroid carcinoma: a systematic review and meta-analysis","volume":"13","author":"Kotanidou","year":"2023","journal-title":"Diagnostics (Basel)"},{"issue":"2","key":"2026102111431647500_dgag418-B22","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s12022-017-9470-y","article-title":"Frequent BRAF V600E and absence of TERT promoter mutations characterize sporadic pediatric papillary thyroid carcinomas in Japan","volume":"28","author":"Oishi","year":"2017","journal-title":"Endocr Pathol"},{"issue":"1","key":"2026102111431647500_dgag418-B23","doi-asserted-by":"crossref","first-page":"12674","DOI":"10.1038\/s41598-022-16207-1","article-title":"The clinical significance of BRAFV600E mutations in pediatric papillary thyroid carcinomas","volume":"12","author":"Li","year":"2022","journal-title":"Sci Rep"},{"issue":"1","key":"2026102111431647500_dgag418-B24","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1093\/ejendo\/lvaf133","article-title":"Autoimmune thyroiditis in paediatric thyroid cancer: clinical features and outcomes","volume":"193","author":"Kuhlen","year":"2025","journal-title":"Eur J Endocrinol"},{"issue":"19","key":"2026102111431647500_dgag418-B25","doi-asserted-by":"crossref","first-page":"4902","DOI":"10.3390\/cancers15194902","article-title":"Hashimoto's thyroiditis and the risk of papillary thyroid cancer in children","volume":"15","author":"Gallant","year":"2023","journal-title":"Cancers (Basel)"},{"key":"2026102111431647500_dgag418-B26","article-title":"A novel risk stratification model based on tumor size and multifocality to predict recurrence in pediatric PTC: comparison with adult PTC","volume":"14","author":"Du","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2026102111431647500_dgag418-B27","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.semcancer.2019.05.019","article-title":"Thyroid autoimmune disorders and cancer","volume":"64","author":"Ferrari","year":"2020","journal-title":"Semin Cancer Biol"},{"issue":"39","key":"2026102111431647500_dgag418-B28","article-title":"Single-cell RNA sequencing reveals the heterogeneity in differentiation trajectory and tumor microenvironment leading to more aggressive phenotypes of papillary thyroid cancer in children and young adult patients","volume":"12","author":"Guo","year":"2025","journal-title":"Adv Sci (Weinh)"},{"key":"2026102111431647500_dgag418-B29","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2025.1551271","article-title":"Mechanisms underlying the promotion of papillary thyroid carcinoma occurrence and progression by Hashimoto's thyroiditis","volume":"16","author":"Xue","year":"2025","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"8","key":"2026102111431647500_dgag418-B30","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.3390\/cancers13081932","article-title":"NTRK fusion genes in thyroid carcinomas: clinicopathological characteristics and their impacts on prognosis","volume":"13","author":"Pekova","year":"2021","journal-title":"Cancers (Basel)"},{"issue":"12","key":"2026102111431647500_dgag418-B31","doi-asserted-by":"crossref","DOI":"10.1530\/ERC-23-0117","article-title":"RET fusion genes in pediatric and adult thyroid carcinomas: cohort characteristics and prognosis","volume":"30","author":"Bulanova Pekova","year":"2023","journal-title":"Endocr Relat Cancer"},{"issue":"10","key":"2026102111431647500_dgag418-B32","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1200\/JCO.21.01861","article-title":"Fusion oncogenes are associated with increased metastatic capacity and persistent disease in pediatric thyroid cancers","volume":"40","author":"Franco","year":"2022","journal-title":"J Clin Oncol"},{"key":"2026102111431647500_dgag418-B33","first-page":"827","volume-title":"Paediatric Tumours","author":"Faquin","year":"2022"},{"issue":"12","key":"2026102111431647500_dgag418-B34","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1089\/thy.2019.0802","article-title":"RET, NTRK, ALK, BRAF, and MET fusions in a large cohort of pediatric papillary thyroid carcinomas","volume":"30","author":"Pekova","year":"2020","journal-title":"Thyroid"},{"issue":"3","key":"2026102111431647500_dgag418-B35","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.cell.2014.09.050","article-title":"Integrated genomic characterization of papillary thyroid carcinoma","volume":"159","author":"Cancer Genome Atlas Research Network","year":"2014","journal-title":"Cell"},{"issue":"11","key":"2026102111431647500_dgag418-B36","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1089\/thy.2021.0003","article-title":"Clinical and molecular characterizations of papillary thyroid cancer in children and young adults: a multicenter retrospective study","volume":"31","author":"Guo","year":"2021","journal-title":"Thyroid"},{"issue":"2","key":"2026102111431647500_dgag418-B37","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1210\/clinem\/dgad500","article-title":"Fusion oncogenes in patients with locally advanced or distant metastatic differentiated thyroid cancer","volume":"109","author":"Ju","year":"2024","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"2026102111431647500_dgag418-B38","article-title":"A nationwide review of pediatric total thyroidectomy and lobectomy outcomes","volume":"10","author":"Jawadi","year":"2025","journal-title":"Laryngoscope Investig Otolaryngol"},{"key":"2026102111431647500_dgag418-B39","doi-asserted-by":"crossref","DOI":"10.1016\/j.suronc.2024.102120","article-title":"Radioactive iodine ablation therapy reduces the risk of recurrent disease in pediatric differentiated thyroid carcinoma","volume":"56","author":"Toraih","year":"2024","journal-title":"Surg Oncol"},{"issue":"7","key":"2026102111431647500_dgag418-B40","doi-asserted-by":"crossref","first-page":"e2403","DOI":"10.1210\/clinem\/dgae656","article-title":"Selective use of radioiodine in pediatric thyroid cancer\u2014a paradigm shift","volume":"110","author":"Robenshtok","year":"2025","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"2026102111431647500_dgag418-B41","doi-asserted-by":"crossref","first-page":"e208","DOI":"10.1210\/clinem\/dgae576","article-title":"Pediatric papillary thyroid carcinoma: outcomes after surgery without adjuvant radioactive iodine","volume":"110","author":"Castellanos","year":"2025","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"2026102111431647500_dgag418-B42","doi-asserted-by":"crossref","first-page":"107","DOI":"10.3390\/cancers17010107","article-title":"The impact of radioactive iodine on outcomes among pediatric and adolescent thyroid cancer patients: a SEER database analysis","volume":"17","author":"Persons","year":"2025","journal-title":"Cancers (Basel)"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgag418\/71836602\/dgag418.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgag418\/71836602\/dgag418.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:43:27Z","timestamp":1792597407000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article\/doi\/10.1210\/clinem\/dgag418\/8907152"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,10]]},"references-count":42,"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgag418","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,10]]},"article-number":"dgag418"}}