problendoПроблемы ЭндокринологииProblems of Endocrinology0375-96602308-1430Endocrinology Research Centre10.14341/probl13649problendo-13649Research ArticleДетская эндокринологияPediatric EndocrinologyРезистентный к радиойодтерапии дифференцированный рак щитовидной железы у детей и подростков. Ретроспективное исследованиеRadioiodine-Refractory Differentiated Thyroid Carcinoma in Children and Adolescents: A Retrospective Studyhttps://orcid.org/0000-0002-3220-2438СлащукК. Ю.SlaschukK. Yu.

Слащук Константин Юрьевич - к.м.н.

Москва

Konstantin Yu. Slashchuk - MD, PhD.

Moscow

slashuk911@gmail.comhttps://orcid.org/0009-0002-1632-2197РейнбергМ. В.ReinbergM. V.

Рейнберг Мария Валентиновна

117036, Москва, улица Дм. Ульянова, д. 11

Maria V. Reinberg

1 Dm. Ulyanova street, 117036 Moscow

mreinberg911@gmail.comhttps://orcid.org/0000-0002-7721-634XРумянцевП. О.RumyantsevP. O.

Румянцев Павел Олегович - профессор, д.м.н.

Москва

Pavel O. Rumyantsev – PhD, MD.

Moscow

pavelrum@gmail.comhttps://orcid.org/0000-0003-4031-5050НикифоровичП. А.NikiforovichP. A.

Никифорович Петр Алексеевич - к.м.н.

Москва

Petr A. Nikiforovich - MD.

Moscow

nikiforovichdoc@gmail.comhttps://orcid.org/0000-0002-6043-3575КононыхинаА. П.KonokikhinaA. P.

Кононыхина Анастасия Павловна

Москва

Anastasia P. Kononykhina – MD.

Moscow

akononykhina1@gmail.comhttps://orcid.org/0000-0002-9462-8522Першина-МилютинаА. П.Pershina-MilyutinaA. P.

Першина-Милютина Анастасия Павловна

Москва

Anastasiia P. Pershina-Miliutina – MD.

Moscow

oa11111998@gmail.comhttps://orcid.org/0009-0007-1336-4152АредовА. В.AredovA. V.

Аредов Алексей Вячеславович

Москва

Aleksey V. Aredov

Moscow

aredov.aleksey@endocrincentr.ruhttps://orcid.org/0000-0003-3785-0335ШереметаМ. С.SheremetaM. S.

Шеремета Марина Сергеевна - д.м.н.

Москва

Marina S. Sheremeta – MD, PhD.

Moscow

marina888@yandex.ruhttps://orcid.org/0000-0001-5652-2607ДегтяревМ. В.DegtyarevM. V.

Дегтярев Михаил Владимирович

Москва

Mikhail V. Degtyarev – MD.

Moscow

germed@mail.ruhttps://orcid.org/0000-0001-5592-4727ТрухинА. А.TrukhinA. A.

Трухин Алексей Андреевич - к.т.н.

Москва

Alexey A. Trukhin - PhD.

Moscow

Alexey.trukhin12@gmail.comhttps://orcid.org/0000-0002-4743-4661ЧикулаеваО. А.ChikulaevaO. A.

Чикулаева Ольга Александровна - к.м.н.

Москва

Olga A. Chikulaeva - .MD, PhD

Moscow

chikulaeva.olga@gmail.comhttps://orcid.org/0000-0001-6429-7198НагаеваЕ. В.NagaevaE. V.

Нагаева Елена Витальевна - д.м.н.

Москва

Elena V. Nagaeva - MD, PhD.

Moscow

nagaeva.ev@mail.ruhttps://orcid.org/0000-0002-3734-6510БровинД. Н.BrovinD. N.

Бровин Дмитрий Николаевич - к.м.н.

Москва

Dmitriy N. Brovin - MD, PhD.

Moscow

brovin-dn@yandex.ruhttps://orcid.org/0000-0002-3001-664XЧерниковР. А.ChernikovR. A.

Черников Роман Анатольевич - д.м.н.

Санкт-Петербург

Roman A. Chernikov - MD, PhD, surgeon.

Saint Petersburg

yaddd@yandex.ruhttps://orcid.org/0000-0001-9621-5732БезлепкинаО. Б.BezlepkinaO. B.

Безлепкина Ольга Борисовна - д.м.н., профессор.

Москва

Olga B. Bezlepkina - .MD, PhD, Professor.

Moscow

olga.bezlepkina@endocrincentr.ruhttps://orcid.org/0000-0002-5507-4627ПетерковаВ. А.PeterkovaV. A.

Петеркова Валентина Александровна - д.м.н., профессор, академик РАН.

Москва

Valentina A. Peterkova - PhD, professor, academician of RAS.

Moscow

peterkovava@hotmail.comhttps://orcid.org/0000-0002-9717-9742МокрышеваН. Г.MokryshevaN. G.

Мокрышева Наталья Георгиевна - д.м.н., профессор.

Москва

Natalia G. Mokrysheva - .MD, PhD, Professor.

Moscow

mokrisheva.natalia@endocrincentr.ruhttps://orcid.org/0000-0002-8175-7886ДедовИ. И.DedovI. I.

Дедов Иван Иванович - д.м.н., профессор, академик РАН.

Москва

Ivan I. Dedov - MD, PhD, Professor, Academician of the RAS.

Moscow

dedov@endocrincentr.ruНациональный медицинский исследовательский центр эндокринологии им. академика И.И. ДедоваРоссияNational Medical Research Center for Endocrinology named after Academician I.I. DedovRussian FederationМой Медицинский Центр «Высокие технологии»РоссияMy Medical Center High TechnologiesRussian FederationНациональный медицинский исследовательский центр нейрохирургии им. академика Н.Н. БурденкоРоссияN.N. Burdenko National Medical Research Center for NeurosurgeryRussian FederationСанкт-Петербургский государственный университет» Клиника высоких медицинских технологий имени Н.И. ПироговаРоссияSaint Petersburg State UniversityRussian Federation2026220720267236679Copyright © Слащук К.Ю., Рейнберг М.В., Румянцев П.О., Никифорович П.А., Кононыхина А.П., Першина-Милютина А.П., Аредов А.В., Шеремета М.С., Дегтярев М.В., Трухин А.А., Чикулаева О.А., Нагаева Е.В., Бровин Д.Н., Черников Р.А., Безлепкина О.Б., Петеркова В.А., Мокрышева Н.Г., Дедов И.И., 20262026Слащук К.Ю., Рейнберг М.В., Румянцев П.О., Никифорович П.А., Кононыхина А.П., Першина-Милютина А.П., Аредов А.В., Шеремета М.С., Дегтярев М.В., Трухин А.А., Чикулаева О.А., Нагаева Е.В., Бровин Д.Н., Черников Р.А., Безлепкина О.Б., Петеркова В.А., Мокрышева Н.Г., Дедов И.И.Slaschuk K.Y., Reinberg M.V., Rumyantsev P.O., Nikiforovich P.A., Konokikhina A.P., Pershina-Milyutina A.P., Aredov A.V., Sheremeta M.S., Degtyarev M.V., Trukhin A.A., Chikulaeva O.A., Nagaeva E.V., Brovin D.N., Chernikov R.A., Bezlepkina O.B., Peterkova V.A., Mokrysheva N.G., Dedov I.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.probl-endojournals.ru/jour/article/view/13649ВВЕДЕНИЕ

ВВЕДЕНИЕ. Дифференцированный рак щитовидной железы (ДРЩЖ) у детей — редкое заболевание, характеризующееся склонностью к регионарному и отдаленному метастазированию, однако при этом имеющее благоприятный долгосрочный прогноз в большинстве случаев. Радиойодрезистентные (РЙР) формы заболевания представляют собой особую клиническую проблему, которая может составлять 10–30% всех случаев ДРЩЖ и требует углубленного изучения клинического течения, факторов прогноза и возможностей терапии данной подгруппы. Цель данного исследования — комплексная оценка исходов лечения у детей, получивших комбинированное лечение по поводу ДРЩЖ (операция и радиойодтерапия (РЙТ)), с акцентом на распространенные и РЙР формы заболевания.

МАТЕРИАЛЫ И МЕТОДЫ

МАТЕРИАЛЫ И МЕТОДЫ. Ретроспективно проанализированы медицинские данные 278 пациентов в возрасте от 5 до 18 лет, перенесших первичное хирургическое лечение в период с 2008 по 2022 гг. и получивших один или несколько курсов РЙТ в ФГБУ «НМИЦ эндокринологии им. академика И.И. Дедова» Минздрава России с декабря 2015 по март 2024 гг. В исследование включены пациенты с распространенным заболеванием (высокий риск рецидива на момент диагностики) и соответствующие одному из критериев РЙР, с медианой наблюдения 48,0 месяцев [21,5; 62,0].

РЕЗУЛЬТАТЫ

РЕЗУЛЬТАТЫ. Из 278 пациентов у 39 (14%) выявлено распространенное заболевание, среди них 4 пациента достигли ремиссии, 29 — стабилизации, 6 — биохимического/структурного прогрессирования. Выживаемость без прогрессирования в группе РЙР пациентов составила 85%, 5-летняя общая выживаемость — 100%.

ЗАКЛЮЧЕНИЕ

ЗАКЛЮЧЕНИЕ. По результатам исследования предложена новая классификация, основанная на исходной способности метастазов накапливать 131I и динамической оценке ответа на лечение после РЙТ (прогрессирование или стабилизация). Эта система направлена на оптимизацию алгоритмов лечения и наблюдения. Стратегия ведения детей с РЙР ДРЩЖ должна быть сбалансированной: с одной стороны — избегать избыточной терапии при стабильном течении заболевания, с другой — своевременно применять современные системные подходы при наличии факторов риска прогрессирования заболевания.

BACKGROUND

BACKGROUND: Differentiated thyroid carcinoma (DTC) in children is a rare malignancy characterized by a high propensity for regional and distant metastases yet generally associated with a favorable long-term prognosis. Radioiodine-refractory (RAIR) disease represents a distinct clinical challenge, accounting for approximately 10–30% of pediatric DTC cases, and warrants comprehensive investigation of its clinical course, prognostic factors, and therapeutic options. This study aimed to perform an integrated assessment of treatment outcomes in children undergoing combined therapy for DTC (surgery and radioiodine therapy, RAI), with a particular focus on advanced and RAIR disease.

MATERIALS AND METHODS

MATERIALS AND METHODS: We retrospectively analyzed medical records of 278 patients aged 5–18 years who underwent primary surgical treatment between 2008 and 2022, followed by one or more courses of RAI at the Endocrinology Research Centre (Moscow, Russia) from December 2015 to March 2024. The study included patients with advanced disease (high risk of recurrence at diagnosis) fulfilling at least one RAIR criterion, with a median follow-up of 48.0 months [21.5; 62.0].

RESULTS

RESULTS: Among 278 patients, 39 (14%) were diagnosed with advanced disease. Of these, 4 achieved remissions, 29 had stable disease, and 6 experienced biochemical and/or structural progression. Progression-free survival in the RAIR cohort was 85%, while the 5-year overall survival reached 100%.

CONCLUSION

CONCLUSION: Based on study findings, we propose a novel classification system integrating both the baseline ability of metastases to accumulate ¹³¹I and the dynamic response to RAI (progression vs. stabilization). This framework is designed to optimize treatment and follow-up algorithms. The management of RAIR pediatric DTC should remain balanced: avoiding overtreatment in stable disease, while ensuring timely initiation of modern systemic therapies in patients with risk factors for progression.

дифференцированный рак щитовидной железыдетиподросткитерапия радиоактивным йодомрезистентность к радиойодтерапиитаргетная терапияdifferentiated thyroid carcinomachildrenadolescentsradioiodine therapyradioiodine­refractory diseasetargeted therapyРабота по подготовке рукописи проведена в рамках государственного задания «Исследование фармакобезопасности тераностических радиофармацевтических лекарственных препаратов с использованием гибридной молекулярной визуализации в диагностике и лечении эндокринных и онкологических заболеваний в детской и взрослой возрастных группах». Регистрационный №ЕГИСУ НИОКТР 123021000041-6ReferencesДетская онкология. Национальное руководство / под ред. М.Д. Алиева, В.Г. Полякова, Г.Л. Менткевича, С.А. Маяковой. М.: Издательская группа РОНЦ. Практическая медицина, 2012Detskaya onkologiya. Nacional'noe rukovodstvo / pod red. MD Alieva, VG Polyakova, GL Mentkevicha, SA Mayakovoj. M.: Izdatel'skaya gruppa RONC. Prakticheskaya medicina, 2012 (In Russ.)]Злокачественные новообразования в России в 2021 году (заболеваемость и смертность) / под ред. А.Д. Каприна, В.В. Старинского, А.О. Шахзадовой. Москва: МНИОИ им. П.А. Герцена − филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2022Zlokachestvennye novoobrazovaniya v Rossii v 2021 godu (zabolevaemost' i smertnost') / pod red. AD Kaprina, VV Starinskogo, AO Shahzadovoj. Moskva: MNIOI im. P.A. Gercena − filial FGBU «NMIC radiologii» Minzdrava Rossii, 2022 (In Russ.)Waguespack S, Wells S, Ross J, Bleyer A. Thyroid Cancer. National Cancer Institute, Bethesda, MD. 2006Waguespack S, Wells S, Ross J, Bleyer A. Thyroid Cancer. National Cancer Institute, Bethesda, MD. 2006Nikiforov YE, Nikiforova MN. Molecular genetics and diagnosis of thyroid cancer. Nature Reviews Endocrinology. 2011;7:569–580Nikiforov YE, Nikiforova MN. Molecular genetics and diagnosis of thyroid cancer. Nature Reviews Endocrinology. 2011;7:569–580Alzahrani AS, Murugan AK, Qasem E, Alswailem M, Al-Hindi H, Shi Y. Single Point Mutations in Pediatric Differentiated Thyroid Cancer. Thyroid. 2017 Feb;27(2):189-196. doi: https://doi.org/10.1089/thy.2016.0339Alzahrani AS, Murugan AK, Qasem E, Alswailem M, Al-Hindi H, Shi Y. Single Point Mutations in Pediatric Differentiated Thyroid Cancer. Thyroid. 2017 Feb;27(2):189-196. doi: https://doi.org/10.1089/thy.2016.0339Prasad, M.L., Vyas, M., Horne, M.J., et al. NTRK fusion oncogenes in pediatric papillary thyroid carcinoma in northeast United States. Cancer. 2016;122:1097-1107. doi: https://doi.org/10.1002/cncr.29887Prasad, M.L., Vyas, M., Horne, M.J., et al. NTRK fusion oncogenes in pediatric papillary thyroid carcinoma in northeast United States. Cancer. 2016;122:1097-1107. doi: https://doi.org/10.1002/cncr.29887Vassilopoulou-Sellin R, Goepfert H, Raney B, Schultz PN. Differentiated thyroid cancer in children and adolescents: clinical outcome and mortality after long-term follow-up. Head Neck. 1998;20(6):549-55. doi: https://doi.org/10.1002/(sici)1097-0347(199809)20:6<549::aid-hed10>3.0.co;2-rVassilopoulou-Sellin R, Goepfert H, Raney B, Schultz PN. Differentiated thyroid cancer in children and adolescents: clinical outcome and mortality after long-term follow-up. Head Neck. 1998;20(6):549-55. doi: https://doi.org/10.1002/(sici)1097-0347(199809)20:6<549::aid-hed10>3.0.co;2-rZimmerman D, Hay ID, Gough IR, Goellner JR, Ryan JJ, Grant CS, McConahey WM. Papillary thyroid carcinoma in children and adults: long-term follow-up of 1039 patients conservatively treated at one institution during three decades. Surgery. 1988;104(6):1157-66Zimmerman D, Hay ID, Gough IR, Goellner JR, Ryan JJ, Grant CS, McConahey WM. Papillary thyroid carcinoma in children and adults: long-term follow-up of 1039 patients conservatively treated at one institution during three decades. Surgery. 1988;104(6):1157-66Brink JS, van Heerden JA, McIver B, Salomao DR, Farley DR, Grant CS, Thompson GB, Zimmerman D, Hay ID. Papillary thyroid cancer with pulmonary metastases in children: long-term prognosis. Surgery. 2000;128(6):881-6; discussion 886-7. doi: https://doi.org/10.1067/msy.2000.109728Brink JS, van Heerden JA, McIver B, Salomao DR, Farley DR, Grant CS, Thompson GB, Zimmerman D, Hay ID. Papillary thyroid cancer with pulmonary metastases in children: long-term prognosis. Surgery. 2000;128(6):881-6; discussion 886-7. doi: https://doi.org/10.1067/msy.2000.109728Prasad PK, Mahajan P, Hawkins DS, Mostoufi-Moab S, Venkatramani R. Management of pediatric differentiated thyroid cancer: An overview for the pediatric oncologist. Pediatr Blood Cancer. 2020;67(6):e28141. doi: https://doi.org/10.1002/pbc.28141Prasad PK, Mahajan P, Hawkins DS, Mostoufi-Moab S, Venkatramani R. Management of pediatric differentiated thyroid cancer: An overview for the pediatric oncologist. Pediatr Blood Cancer. 2020;67(6):e28141. doi: https://doi.org/10.1002/pbc.28141Stosic A, Fuligni F, Anderson ND, et al. Diverse oncogenic fusions and distinct gene expression patterns define the genomic landscape of pediatric papillary thyroid carcinoma. Cancer Research. 2021;81(22):5625e37Stosic A, Fuligni F, Anderson ND, et al. Diverse oncogenic fusions and distinct gene expression patterns define the genomic landscape of pediatric papillary thyroid carcinoma. Cancer Research. 2021;81(22):5625e37Penko K, Livezey J, Fenton C, et al. BRAF mutations are uncommon in papillary thyroid cancer of young patients. Thyroid. 2005;15:320–325Penko K, Livezey J, Fenton C, et al. BRAF mutations are uncommon in papillary thyroid cancer of young patients. Thyroid. 2005;15:320–325Rosenbaum E, Hosler G, Zahurak M, Cohen Y, Sidransky D, Westra WH. Mutational activation of BRAF is not a major event in sporadic childhood papillary thyroid carcinoma. Mod Pathol. 2005;18(7):898-902. doi: https://doi.org/10.1038/modpathol.3800252Rosenbaum E, Hosler G, Zahurak M, Cohen Y, Sidransky D, Westra WH. Mutational activation of BRAF is not a major event in sporadic childhood papillary thyroid carcinoma. Mod Pathol. 2005;18(7):898-902. doi: https://doi.org/10.1038/modpathol.3800252Van Nostrand D. Radioiodine Refractory Differentiated Thyroid Cancer: Time to Update the Classifications. Thyroid. 2018;28(9):1083-1093. doi: https://doi.org/10.1089/thy.2018.0048Van Nostrand D. Radioiodine Refractory Differentiated Thyroid Cancer: Time to Update the Classifications. Thyroid. 2018;28(9):1083-1093. doi: https://doi.org/10.1089/thy.2018.0048Tian T., Shuhui H., Hongyuan D., Mengfang Q., Bin L., Rui H., Radioactive Iodine-Refractory Pulmonary Metastases of Papillary Thyroid Cancer in Children, Adolescents, and Young Adults. // The Journal of Clinical Endocrinology & Metabolism. 2023. Vol. 108, Iss. 2. P. 306–314 doi:10.1210/clinem/dgac600Tian T., Shuhui H., Hongyuan D., Mengfang Q., Bin L., Rui H., Radioactive Iodine-Refractory Pulmonary Metastases of Papillary Thyroid Cancer in Children, Adolescents, and Young Adults. // The Journal of Clinical Endocrinology & Metabolism. 2023. Vol. 108, Iss. 2. P. 306–314 doi:10.1210/clinem/dgac600de Sousa MSA, Nunes IN, Christiano YP, Sisdelli L, Cerutti JM. Genetic alterations landscape in pediatric thyroid tumours and/or differentiated thyroid cancer: Systematic review. Review Endocrinology Metabolism Disorders. 2023de Sousa MSA, Nunes IN, Christiano YP, Sisdelli L, Cerutti JM. Genetic alterations landscape in pediatric thyroid tumours and/or differentiated thyroid cancer: Systematic review. Review Endocrinology Metabolism Disorders. 2023Christine EC,, et al. Pediatric thyroid cancer: Recent developments. Research Clinical Endocrinology & Metabolism. 2022;37(1):101715Christine EC,, et al. Pediatric thyroid cancer: Recent developments. Research Clinical Endocrinology & Metabolism. 2022;37(1):101715Gallant J.N., Chen S.C., Ortega C.A., et al. Evaluation of the molecular landscape of pediatric thyroid nodules and use of a multigene genomic classifier in children. // JAMA Oncol. 2022;8(9):1323-1327. doi:10.1001/jamaoncol.2022.1655Gallant J.N., Chen S.C., Ortega C.A., et al. Evaluation of the molecular landscape of pediatric thyroid nodules and use of a multigene genomic classifier in children. // JAMA Oncol. 2022;8(9):1323-1327. doi:10.1001/jamaoncol.2022.1655Hess JR, Newbern DK, Beebe KL, et al. High prevalence of gene fusions and copy number alterations in pediatric radiation therapy-induced papillary and follicular thyroid carcinomas. Thyroid 2022;32(4):411e20Hess JR, Newbern DK, Beebe KL, et al. High prevalence of gene fusions and copy number alterations in pediatric radiation therapy-induced papillary and follicular thyroid carcinomas. Thyroid 2022;32(4):411e20Wasserman JD, Sabbaghian N, Fahiminiya S, et al. DICER1 mutations are frequent in adolescent-onset papillary thyroid carcinoma. Journal of Clinical Endocrinology and Metabolism. 2018;103(5):2009e15Wasserman JD, Sabbaghian N, Fahiminiya S, et al. DICER1 mutations are frequent in adolescent-onset papillary thyroid carcinoma. Journal of Clinical Endocrinology and Metabolism. 2018;103(5):2009e15Chernock RD, Rivera B, Borrelli N, et al. Poorly differentiated thyroid carcinoma of childhood and adolescence: a distinct entity characterized by DICER1 mutations. Modern Pathology. 2020;33(7):1264e74Chernock RD, Rivera B, Borrelli N, et al. Poorly differentiated thyroid carcinoma of childhood and adolescence: a distinct entity characterized by DICER1 mutations. Modern Pathology. 2020;33(7):1264e74Marcia SB, Christopher N, Barbara J, Rossella E, Salvatore S, Lars B. Sorafenib in locally advanced or metastatic patients with radioactive iodine-refractory differentiated thyroid cancer: The phase III DECISION trial. Lancet. 2014;26(384(9940):319-28Marcia SB, Christopher N, Barbara J, Rossella E, Salvatore S, Lars B. Sorafenib in locally advanced or metastatic patients with radioactive iodine-refractory differentiated thyroid cancer: The phase III DECISION trial. Lancet. 2014;26(384(9940):319-28Mahajan P, Dawrant J, Kheradpour A, et al. Response to Lenvatinib in Children with Papillary Thyroid Carcinoma. Thyroid. 2018;28(11):1450-1454Mahajan P, Dawrant J, Kheradpour A, et al. Response to Lenvatinib in Children with Papillary Thyroid Carcinoma. Thyroid. 2018;28(11):1450-1454Dadu R, Shah K, Busaidy NL, et al. Efficacy and tolerability of vemurafenib in patients with BRAF (V600E)-positive papillary thyroid cancer: M.D. Anderson Cancer Center off-label experience. Journal of Clinical Endocrinology and Metabolism. 2015;100(1):77Dadu R, Shah K, Busaidy NL, et al. Efficacy and tolerability of vemurafenib in patients with BRAF (V600E)-positive papillary thyroid cancer: M.D. Anderson Cancer Center off-label experience. Journal of Clinical Endocrinology and Metabolism. 2015;100(1):77Ho AL, Grewal RK, Leboeuf R., et al. Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer. New English Journal of Medicine. 2013;368(7):623-632Ho AL, Grewal RK, Leboeuf R., et al. Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer. New English Journal of Medicine. 2013;368(7):623-632Steven GW, Alexander D, Jessica JL, et al. Efficacy and safety of larotrectinib in patients with TRK fusion-positive thyroid carcinoma. European Journal of Endocrinology. 2022;186(Iss.6):631–643Steven GW, Alexander D, Jessica JL, et al. Efficacy and safety of larotrectinib in patients with TRK fusion-positive thyroid carcinoma. European Journal of Endocrinology. 2022;186(Iss.6):631–643Desai AV, Robinson GW, Gauvain K, et al. Entrectinib in children and young adults with solid or primary CNS tumors harboring NTRK, ROS1, or ALK aberrations (STARTRK-NG). Neuro-Oncology. 2022;24(10):1776-1789Desai AV, Robinson GW, Gauvain K, et al. Entrectinib in children and young adults with solid or primary CNS tumors harboring NTRK, ROS1, or ALK aberrations (STARTRK-NG). Neuro-Oncology. 2022;24(10):1776-1789Wirth LJ, Sherman E, Robinson B, et al. Efficacy of selpercatinib in RET-altered thyroid cancers. The New England Journal of Medicine. 2020;383(9):825e35Wirth LJ, Sherman E, Robinson B, et al. Efficacy of selpercatinib in RET-altered thyroid cancers. The New England Journal of Medicine. 2020;383(9):825e35Subbiah V, Hu MI, Mansfield AS, et al. Pralsetinib in Patients with Advanced/Metastatic Rearranged During Transfection (RET)Altered Thyroid Cancer: Updated Efficacy and Safety Data from the ARROW Study [published correction appears in Thyroid. 2024 Apr 16. doi: 10.1089/thy.2023.0363.correx.]. Thyroid. 2024;34(1):26-40. doi: https://doi.org/10.1089/thy.2023.0363Subbiah V, Hu MI, Mansfield AS, et al. Pralsetinib in Patients with Advanced/Metastatic Rearranged During Transfection (RET)Altered Thyroid Cancer: Updated Efficacy and Safety Data from the ARROW Study [published correction appears in Thyroid. 2024 Apr 16. doi: 10.1089/thy.2023.0363.correx.]. Thyroid. 2024;34(1):26-40. doi: https://doi.org/10.1089/thy.2023.0363Kieran MW, Geoerger B, Dunkel IJ, Broniscer A, Hargrave D, Hingorani P, Aerts I, et al. A Phase I and Pharmacokinetic Study of Oral Dabrafenib in Children and Adolescent Patients with Recurrent or Refractory BRAF V600 MutationPositive Solid Tumors. Clin Cancer Res. 2019;25(24):7294-7302. doi: https://doi.org/10.1158/1078-0432.CCR-17-3572Kieran MW, Geoerger B, Dunkel IJ, Broniscer A, Hargrave D, Hingorani P, Aerts I, et al. A Phase I and Pharmacokinetic Study of Oral Dabrafenib in Children and Adolescent Patients with Recurrent or Refractory BRAF V600 MutationPositive Solid Tumors. Clin Cancer Res. 2019;25(24):7294-7302. doi: https://doi.org/10.1158/1078-0432.CCR-17-3572Tuttle M, Morris LF, Haugen B, Shah J, Sosa JA, Rohren E, Subramaniam RM, Hunt JL & Perrier ND 2017b Thyroid-differentiated and anaplastic carcinoma (Chapter 73). In AJCC Cancer Staging Manual, 8th editionTuttle M, Morris LF, Haugen B, Shah J, Sosa JA, Rohren E, Subramaniam RM, Hunt JL & Perrier ND 2017b Thyroid-differentiated and anaplastic carcinoma (Chapter 73). In AJCC Cancer Staging Manual, 8th editionKakudo K, Bychkov A, Bai Y, Li Y, Liu Z, Jung CK. The new 4th edition World Health Organization classification for thyroid tumors, Asian perspectives. Pathol Int. 2018;68:641-664. doi: https://doi.org/10.1111/pin.12737Kakudo K, Bychkov A, Bai Y, Li Y, Liu Z, Jung CK. The new 4th edition World Health Organization classification for thyroid tumors, Asian perspectives. Pathol Int. 2018;68:641-664. doi: https://doi.org/10.1111/pin.12737Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). European journal of cancer (Oxford, England: 1990). 2009;45(2):228–247. doi: https://doi.org/10.1016/j.ejca.2008.10.026Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). European journal of cancer (Oxford, England: 1990). 2009;45(2):228–247. doi: https://doi.org/10.1016/j.ejca.2008.10.026Tamer F, Güven M, Oral A, Yazici B, Akgün A. Which factors affect treatment success/prognosis in thyroid cancers with pulmonary metastases and what is/how should be the effective cumulative cure/dose as a current approach; a retrospective study. Ann Nucl Med. Published online May 19, 2025. doi: https://doi.org/10.1007/s12149-025-02060-5Tamer F, Güven M, Oral A, Yazici B, Akgün A. Which factors affect treatment success/prognosis in thyroid cancers with pulmonary metastases and what is/how should be the effective cumulative cure/dose as a current approach; a retrospective study. Ann Nucl Med. Published online May 19, 2025. doi: https://doi.org/10.1007/s12149-025-02060-5Durante C, Haddy N, Baudin E, et al. Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy. J Clin Endocrinol Metab. 2006;91:2892–2899. doi: https://doi.org/10.1210/jc.2005-2838Durante C, Haddy N, Baudin E, et al. Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy. J Clin Endocrinol Metab. 2006;91:2892–2899. doi: https://doi.org/10.1210/jc.2005-2838Marotta V, Rocco D, Crocco A, et al. Survival Predictors of Radioiodine-refractory Differentiated Thyroid Cancer Treated With Lenvatinib in Real Life. J Clin Endocrinol Metab. 2024;109(10):2541-2552. doi: https://doi.org/10.1210/clinem/dgae181Marotta V, Rocco D, Crocco A, et al. Survival Predictors of Radioiodine-refractory Differentiated Thyroid Cancer Treated With Lenvatinib in Real Life. J Clin Endocrinol Metab. 2024;109(10):2541-2552. doi: https://doi.org/10.1210/clinem/dgae181Nakanishi K, Kikumori T, Miyajima N, et al. Impact of Patient Age and Histological Type on Radioactive Iodine Avidity of Recurrent Lesions of Differentiated Thyroid Carcinoma. Clin Nucl Med. 2018;43(7):482-485. doi: https://doi.org/10.1097/RLU.0000000000002078Nakanishi K, Kikumori T, Miyajima N, et al. Impact of Patient Age and Histological Type on Radioactive Iodine Avidity of Recurrent Lesions of Differentiated Thyroid Carcinoma. Clin Nucl Med. 2018;43(7):482-485. doi: https://doi.org/10.1097/RLU.0000000000002078Lang BH, Wong KP, Cheung CY, Wan KY, Lo CY. Evaluating the prognostic factors associated with cancer-specific survival of differentiated thyroid carcinoma presenting with distant metastasis. Ann Surg Oncol. 2013;20(4):1329-1335. doi: https://doi.org/10.1245/s10434-012-2711-xLang BH, Wong KP, Cheung CY, Wan KY, Lo CY. Evaluating the prognostic factors associated with cancer-specific survival of differentiated thyroid carcinoma presenting with distant metastasis. Ann Surg Oncol. 2013;20(4):1329-1335. doi: https://doi.org/10.1245/s10434-012-2711-xTsai HC, Ho KC, Chen SH, Tseng JR, Yang LY, Lin KJ, Cheng JC, Liou MJ. Feasibility of Recombinant Human TSH as a Preparation for Radioiodine Therapy in Patients with Distant Metastases from Papillary Thyroid Cancer: Comparison of Long-Term Survival Outcomes with Thyroid Hormone Withdrawal. Diagnostics. 2022;12(1):221. doi: https://doi.org/10.3390/diagnostics12010221Tsai HC, Ho KC, Chen SH, Tseng JR, Yang LY, Lin KJ, Cheng JC, Liou MJ. Feasibility of Recombinant Human TSH as a Preparation for Radioiodine Therapy in Patients with Distant Metastases from Papillary Thyroid Cancer: Comparison of Long-Term Survival Outcomes with Thyroid Hormone Withdrawal. Diagnostics. 2022;12(1):221. doi: https://doi.org/10.3390/diagnostics12010221Zhuanzhuan Mu, Xin Zhang, Di Sun, Yuqing Sun, Cong Shi, Gaoda Ju, et al. Characterizing Genetic Alterations Related to Radioiodine Avidity in Metastatic Thyroid Cancer, The Journal of Clinical Endocrinology & Metabolism. 2024;109(5):1231–1240. doi: https://doi.org/10.1210/clinem/dgad697Zhuanzhuan Mu, Xin Zhang, Di Sun, Yuqing Sun, Cong Shi, Gaoda Ju, et al. Characterizing Genetic Alterations Related to Radioiodine Avidity in Metastatic Thyroid Cancer, The Journal of Clinical Endocrinology & Metabolism. 2024;109(5):1231–1240. doi: https://doi.org/10.1210/clinem/dgad697Seo GH, Kong KA, Kim BS, et al. Radioactive iodine treatment for children and young adults with thyroid cancer in South Korea: a population-based study. The Journal of Clinical Endocrinology & Metabolism. 2021;106(7):e2580e8Seo GH, Kong KA, Kim BS, et al. Radioactive iodine treatment for children and young adults with thyroid cancer in South Korea: a population-based study. The Journal of Clinical Endocrinology & Metabolism. 2021;106(7):e2580e8Pasqual E, Schonfeld S, Morton LM, et al. Association between radioactive iodine treatment for pediatric and young adulthood differentiated thyroid cancer and risk of second primary malignancies. The Journal of Clinical Oncology. 2022;40(13):1439e49Pasqual E, Schonfeld S, Morton LM, et al. Association between radioactive iodine treatment for pediatric and young adulthood differentiated thyroid cancer and risk of second primary malignancies. The Journal of Clinical Oncology. 2022;40(13):1439e49Sugino K, Nagahama M, Kitagawa W, et al. Distant metastasis in pediatric and adolescent differentiated thyroid cancer: clinical outcomes and risk factor Analyses. The Journal of Clinical Endocrinology & Metabolism. 2020;105:11Sugino K, Nagahama M, Kitagawa W, et al. Distant metastasis in pediatric and adolescent differentiated thyroid cancer: clinical outcomes and risk factor Analyses. The Journal of Clinical Endocrinology & Metabolism. 2020;105:11Klein HMS, Nies M, Bocca G, et al. Pediatric differentiated thyroid carcinoma in The Netherlands: a nationwide follow-up study. The Journal of Clinical Endocrinology & Metabolism. 2016;101(5):2031e9Klein HMS, Nies M, Bocca G, et al. Pediatric differentiated thyroid carcinoma in The Netherlands: a nationwide follow-up study. The Journal of Clinical Endocrinology & Metabolism. 2016;101(5):2031e9Hay ID, Johnson TR, Kaggal S, et al. Papillary thyroid carcinoma (PTC) in children and adults: comparison of initial presentation and longterm postoperative outcome in 4432 patients consecutively treated at the mayo clinic during eight decades (1936-2015). World Journal of Surgery. 2018;42(2):329e42Hay ID, Johnson TR, Kaggal S, et al. Papillary thyroid carcinoma (PTC) in children and adults: comparison of initial presentation and longterm postoperative outcome in 4432 patients consecutively treated at the mayo clinic during eight decades (1936-2015). World Journal of Surgery. 2018;42(2):329e42Shi C, Sun D, Sun YQ, et al. Less is more: once vs. multiple radioactive iodine (RAI) therapy in patients with RAI-avid pulmonary micrometastatic differentiated thyroid cancer. Eur J Nucl Med Mol Imaging. Published online May 26, 2025. doi: https://doi.org/10.1007/s00259-025-07339-3Shi C, Sun D, Sun YQ, et al. Less is more: once vs. multiple radioactive iodine (RAI) therapy in patients with RAI-avid pulmonary micrometastatic differentiated thyroid cancer. Eur J Nucl Med Mol Imaging. Published online May 26, 2025. doi: https://doi.org/10.1007/s00259-025-07339-3Seejore K, Mulla O, Gerrard GE, et al. Outcomes of 756 patients with differentiated thyroid cancer and excellent response to treatment: An evidence-based paradigm for long-term surveillance strategies. Clin Endocrinol (Oxf). 2022;96(3):395-401. doi: https://doi.org/10.1111/cen.14549Seejore K, Mulla O, Gerrard GE, et al. Outcomes of 756 patients with differentiated thyroid cancer and excellent response to treatment: An evidence-based paradigm for long-term surveillance strategies. Clin Endocrinol (Oxf). 2022;96(3):395-401. doi: https://doi.org/10.1111/cen.14549

The authors declare that there are no conflicts of interest present.