A Contemporary Review of the Treatment of Medullary Thyroid Carcinoma in the Era of New Drug Therapies

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Revised American Thyroid Association Guidelines for the Management of Medullary Thyroid Carcinoma.

Thyroid. 25: 567-610Fussey J.M. Vaidya B. Kim D. et al.

The role of molecular genetics in the clinical management of sporadic medullary thyroid carcinoma: A systematic review.

Clin Endocrinol. 91: 697-707Vuong H.G. Odate T. Ngo H.T.T. et al.

Clinical significance of RET and RAS mutations in sporadic medullary thyroid carcinoma: a meta-analysis.

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RAS proto-oncogene in medullary thyroid carcinoma.

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The importance of the RET gene in thyroid cancer and therapeutic implications.

Nat Rev Endocrinol. 17: 296-306Pasini B. Borrello M.G. Greco A. et al.

Loss of function effect of RET mutations causing Hirschsprung disease.

Nat Genet. 10: 35-40Santoro M. Carlomagno F. Romano A. et al.

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A comprehensive overview of the role of the RET proto-oncogene in thyroid carcinoma.

Nat Rev Endocrinol. 12: 192-202

GLOBAL ENDOCRINOLOGY: Geographical variation in the profile of RET variants in patients with medullary thyroid cancer: a comprehensive review.

Eur J Endocrinol. 186: R15-R30Machens A. Niccoli-Sire P. Hoegel J. et al.

Early malignant progression of hereditary medullary thyroid cancer.

N Engl J Med. 349: 1517-1525Skinner M.A. Moley J.A. Dilley W.G. et al.

Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A.

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Outcomes of adrenal-sparing surgery or total adrenalectomy in phaeochromocytoma associated with multiple endocrine neoplasia type 2: an international retrospective population-based study.

Lancet Oncol. 15: 648-655Kebebew E. Ituarte P.H. Siperstein A.E. et al.

Medullary thyroid carcinoma: clinical characteristics, treatment, prognostic factors, and a comparison of staging systems.

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Normal thyroid pathology in patients undergoing thyroidectomy for finding a RETgene germline mutation: a report of three cases and review of the literature.

Thyroid. 9: 127-131Machens A. Elwerr M. Lorenz K. et al.

Long-term outcome of prophylactic thyroidectomy in children carrying RET germline mutations.

Br J Surg. 105: e150-e157Moura M.M. Cavaco B.M. Pinto A.E. et al.

High Prevalence of RAS Mutations in RET-Negative Sporadic Medullary Thyroid Carcinomas.

J Clin Endocrinol Metab. 96: E863-E868Pusztaszeri M.P. Bongiovanni M. Faquin W.C.

Update on the cytologic and molecular features of medullary thyroid carcinoma.

Adv Anat Pathol. 21: 26-35

Barriers to the recognition of medullary thyroid carcinoma on FNA: Implications relevant to the new American Thyroid Association guidelines.

Cancer Cytopathology. 126: 397-405Verbeek H.H. de Groot J.W.B. Sluiter W.J. et al.

Calcitonin testing for detection of medullary thyroid cancer in people with thyroid nodules.

Cochrane Database Syst Rev. : 1-98Wang L. Kou H. Chen W. et al.

The diagnostic value of ultrasound in medullary thyroid carcinoma: a comparison with computed tomography.

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New American Thyroid Association sonographic patterns for thyroid nodules perform well in medullary thyroid carcinoma: institutional experience, systematic review, and meta-analysis.

Thyroid. 26: 1093-1100Yun G. Kim Y.K. Choi S.I. et al.

Medullary thyroid carcinoma: application of thyroid imaging reporting and data system (TI-RADS) classification.

Endocrine. 61: 285-292Giraudet A.L. Vanel D. Leboulleux S. et al.

Imaging medullary thyroid carcinoma with persistent elevated calcitonin levels.

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Detection of liver metastases from endocrine tumors: a prospective comparison of somatostatin receptor scintigraphy, computed tomography, and magnetic resonance imaging.

J Clin Oncol. 23: 70-78Lee S.-W. Shim S.R. Jeong S.Y. et al.

Comparison of 5 different PET radiopharmaceuticals for the detection of recurrent medullary thyroid carcinoma: a network meta-analysis.

Clin Nucl Med. 45: 341-348Treglia G. Castaldi P. Villani M.F. et al.

Comparison of 18F-DOPA, 18F-FDG and 68Ga-somatostatin analogue PET/CT in patients with recurrent medullary thyroid carcinoma.

Eur J Nucl Med Mol Imaging. 39: 569-580Golubić A.T. Pasini Nemir E. Žuvić M. et al.

The value of 18F-DOPA PET/CT in patients with medullary thyroid carcinoma and increased calcitonin values.

Nucl Med Commun. 38: 636-641Treglia G. Cocciolillo F. Di Nardo F. et al.

Detection rate of recurrent medullary thyroid carcinoma using fluorine-18 dihydroxyphenylalanine positron emission tomography: a meta-analysis.

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Diagnostic accuracy of 18F-FDG PET in restaging patients with medullary thyroid carcinoma and elevated calcitonin levels.

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Detection rate of somatostatin receptor PET in patients with recurrent medullary thyroid carcinoma: a systematic review and a meta-analysis.

Hormones. 16: 362-372Giovanella L. Treglia G. Iakovou I. et al.

EANM practice guideline for PET/CT imaging in medullary thyroid carcinoma.

Eur J Nucl Med Mol Imaging. 47: 61-77

Positron Emission Tomography Imaging in Medullary Thyroid Carcinoma: Time for Reappraisal?.

Thyroid. 31: 151-155Perros P. Boelaert K. Colley S. et al.

Guidelines for the management of thyroid cancer.

Clin Endocrinol. 81: 1-122Patel K.N. Yip L. Lubitz C.C. et al.

The American Association of Endocrine Surgeons guidelines for the definitive surgical management of thyroid disease in adults.

Ann Surg. 271: e21-e93

Biomarker-based risk stratification for previously untreated medullary thyroid cancer.

J Clin Endocrinol Metab. 95: 2655-2663Machens A. Lorenz K. Weber F. et al.

Exceptionality of Distant Metastasis in Node-Negative Hereditary and Sporadic Medullary Thyroid Cancer: Lessons Learned.

J Clin Endocrinol Metab. 106: e2968-e2979https://doi.org/10.1210/clinem/dgab214McMullen C. Rocke D. Freeman J.

Complications of bilateral neck dissection in thyroid cancer from a single high-volume center.

JAMA Otolaryngology–Head Neck Surg. 143: 376-381Sosa J.A. Tuggle C.T. Wang T.S. et al.

Clinical and economic outcomes of thyroid and parathyroid surgery in children.

J Clin Endocrinol Metab. 93: 3058-3065Fersht N. Vini L. A'hern R. et al.

The role of radiotherapy in the management of elevated calcitonin after surgery for medullary thyroid cancer.

Thyroid. 11: 1161-1168Brierley J. Tsang R. Simpson W. et al.

Medullary thyroid cancer: analyses of survival and prognostic factors and the role of radiation therapy in local control.

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The role of external beam radiotherapy in the management of medullary carcinoma of the thyroid: A systematic review.

Radiother Oncol. 136: 113-120Wu L.T. Averbuch S.D. Ball D.W. et al.

Treatment of advanced medullary thyroid carcinoma with a combination of cyclophosphamide, vincristine, and dacarbazine.

Cancer. 73: 432-436Nocera M. Baudin E. Pellegriti G. et al.

Treatment of advanced medullary thyroid cancer with an alternating combination of doxorubicin-streptozocin and 5 FU-dacarbazine.

Br J Cancer. 83: 715-718AJCC cancer staging manual. 8th edition. Springer, Chicago, ILEsfandiari N.H. Hughes D.T. Yin H. et al.

The Effect of Extent of Surgery and Number of Lymph Node Metastases on Overall Survival in Patients with Medullary Thyroid Cancer.

J Clin Endocrinol Metab. 99: 448-454Adam M.A. Thomas S. Roman S.A. et al.

Rethinking the Current American Joint Committee on Cancer TNM Staging System for Medullary Thyroid Cancer.

JAMA Surg. 152: 869-876

Prognostic impact of N staging in 715 medullary thyroid cancer patients: proposal for a revised staging system.

Ann Surg. 257: 323-329Wang Z. Tang C. Wang Y. et al.

Inclusion of the Number of Metastatic Lymph Nodes in the Staging System for Medullary Thyroid Cancer: Validating a Modified AJCC TNM Staging System.

Thyroid. https://doi.org/10.1089/thy.2021.0571Yang J.H. Lindsey S.C. Camacho C.P. et al.

Integration of a postoperative calcitonin measurement into an anatomical staging system improves initial risk stratification in medullary thyroid cancer.

Clin Endocrinol. 83: 938-942Barbet J. Campion Lc Kraeber-Bodéré Fo et al.

Prognostic Impact of Serum Calcitonin and Carcinoembryonic Antigen Doubling-Times in Patients with Medullary Thyroid Carcinoma.

J Clin Endocrinol Metab. 90: 6077-6084Alencar R. Kendler D.B. Andrade F. et al.

CA19-9 as a predictor of worse clinical outcome in medullary thyroid carcinoma.

Eur Thyroid J. 8: 186-191Xu B. Fuchs T.L. Ahmadi S. et al.

International Medullary Thyroid Carcinoma Grading System: A Validated Grading System for Medullary Thyroid Carcinoma.

J Clin Oncol. 40: 96-104Saad M.F. Ordonez N.G. Rashid R.K. et al.

Medullary carcinoma of the thyroid. A study of the clinical features and prognostic factors in 161 patients.

Medicine. 63: 319-342Sahli Z.T. Canner J.K. Zeiger M.A. et al.

Association between age and disease specific mortality in medullary thyroid cancer.

Am J Surg. 221: 478-484Miyauchi A. Onishi T. Morimoto S. et al.

Relation of doubling time of plasma calcitonin levels to prognosis and recurrence of medullary thyroid carcinoma.

Ann Surg. 199: 461Yeh T. Yeung M. Sherman E.J. et al.

Structural doubling time predicts overall survival in patients with medullary thyroid cancer in patients with rapidly progressive metastatic medullary thyroid cancer treated with molecular targeted therapies.

Thyroid. 30: 1112-1119Elisei R. Lorusso L. Romei C. et al.

Medullary Thyroid Cancer Secreting Carbohydrate Antigen 19-9 (Ca 19-9): A Fatal Case Report.

J Clin Endocrinol Metab. 98: 3550-3554Milman S. Whitney K.D. Fleischer N.

Metastatic medullary thyroid cancer presenting with elevated levels of CA 19-9 and CA 125.

Thyroid. 21: 913-916Vierbuchen M. Larena A. Schröder S. et al.

Blood group antigen expression in medullary carcinoma of the thyroid. An immunohistochemical study on the occurrence of type 1 chain-derived antigens.

Virchows Arch B Cell Pathol Incl Mol Pathol. 62: 79-88Lorusso L. Romei C. Piaggi P. et al.

Ca19.9 Positivity and Doubling Time Are Prognostic Factors of Mortality in Patients with Advanced Medullary Thyroid Cancer with No Evidence of Structural Disease Progression According to Response Evaluation Criteria in Solid Tumors.

Thyroid. 31: 1050-1055Rodríguez-Antona C. Pallares J. Montero-Conde C. et al.

Overexpression and activation of EGFR and VEGFR2 in medullary thyroid carcinomas is related to metastasis.

Endocrine-Related Cancer. 17: 7-16Wells Jr., S.A. Robinson B.G. Gagel R.F. et al.

Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial.

J Clin Oncol. 30: 134Elisei R. Schlumberger M.J. Müller S.P. et al.

Cabozantinib in progressive medullary thyroid cancer.

J Clin Oncol. 31: 3639Schlumberger M. Elisei R. Müller S. et al.

Overall survival analysis of EXAM, a phase III trial of cabozantinib in patients with radiographically progressive medullary thyroid carcinoma.

Ann Oncol. 28: 2813-2819Schlumberger M. Jarzab B. Cabanillas M.E. et al.

A Phase II Trial of the Multitargeted Tyrosine Kinase Inhibitor Lenvatinib (E7080) in Advanced Medullary Thyroid CancerPhase II Trial of Lenvatinib in Medullary Thyroid Cancer.

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Lenvatinib as a salvage therapy for advanced metastatic medullary thyroid cancer.

J Endocrinological Invest. 44: 2139-2151Lam E.T. Ringel M.D. Kloos R.T. et al.

Phase II clinical trial of sorafenib in metastatic medullary thyroid cancer.

J Clin Oncol. 28: 2323De Souza J. Busaidy N. Zimrin A. et al.

Phase II trial of sunitinib in medullary thyroid cancer (MTC).

J Clin Oncol. 28: 5504Ravaud A. de la Fouchardière C. Caron P. et al.

A multicenter phase II study of sunitinib in patients with locally advanced or metastatic differentiated, anaplastic or medullary thyroid carcinomas: mature data from the THYSU study.

Eur J Cancer. 76: 110-117Chougnet C.N. Borget I. Leboulleux S. et al.

Vandetanib for the treatment of advanced medullary thyroid cancer outside a clinical trial: results from a French cohort.

Thyroid. 25: 386-391Kesby N.L. Papachristos A.J. Gild M. et al.

Outcomes of Advanced Medullary Thyroid Carcinoma in the Era of Targeted Therapy.

Ann Surg Oncol. 29: 64-71

Advances in targeting RET-dependent cancers.

Cancer Discov. 10: 498-505Carlomagno F. Guida T. Anaganti S. et al.

Disease associated mutations at valine 804 in the RET receptor tyrosine kinase confer resistance to selective kinase inhibitors.

Oncogene. 23: 6056-6063Busaidy N. Cabanillas M. Sherman S. et al.

Emergence of V804M resistance gatekeeper mutation in sporadic medullary thyroid carcinoma patients treated with TKI tyrosine kinase inhibitors.

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State-of-the-art strategies for targeting RET-dependent cancers.

J Clin Oncol. 38: 1209Wirth L.J. Sherman E. Robinson B. et al.

Efficacy of Selpercatinib in RET-Altered Thyroid Cancers.

New Engl J Med. 383: 825-835Subbiah V. Hu M.I.-N. Gainor J.F. et al.

Clinical activity of the RET inhibitor pralsetinib (BLU-667) in patients with RET fusion+ solid tumors.

J Clin Oncol. 38: 109Schoffski P. Aftimos P.G. Massard C. et al.

A phase I study of BOS172738 in patients with advanced solid tumors with RET gene alterations including non-small cell lung cancer and medullary thyroid cancer.

Am Soc Clin Oncol. Drilon A. Rogers E. Zhai D. et al.

TPX-0046 is a novel and potent RET/SRC inhibitor for RET-driven cancers.

Ann Oncol. 30: v190-v191Jozaghi Y. Zafereo M. Williams M.D. et al.

Neoadjuvant selpercatinib for advanced medullary thyroid cancer.

Head & Neck. 43: E7-E12Grasic Kuhar C. Lozar T. Besic N. et al.

Outcome of Patients with Locally Advanced Metastatic Medullary Thyroid Cancer and Induction Therapy with Tyrosine Kinase Inhibitors in Slovenia.

Adv Ther. 38: 5684-5699

Selpercatinib Aimed at RET-Altered Cancers.

New Engl J Med. 383: 868-869Grossrubatscher E. Fanciulli G. Pes L. et al.

Advances in the management of medullary thyroid carcinoma: focus on peptide receptor radionuclide therapy.

J Clin Med. 9: 3507

Peptide Receptor Radionuclide Therapy in Patients With Differentiated Thyroid Cancer: A Meta-analysis.

Clin Nucl Med. 45: 604-610Pozdeyev N. Erickson T.A. Zhang L. et al.

Comprehensive immune profiling of medullary thyroid cancer.

Thyroid. 30: 1263-1279

Immunotherapy for advanced thyroid cancers—rationale, current advances and future strategies.

Nat Rev Endocrinol. 16: 629-641Bachleitner-Hofmann T. Friedl J. Hassler M. et al.

Pilot trial of autologous dendritic cells loaded with tumor lysate (s) from allogeneic tumor cell lines in patients with metastatic medullary thyroid carcinoma.

Oncol Rep. 21: 1585-1592Schott M. Feldkamp J. Klucken M. et al.

Calcitonin-specific antitumor immunity in medullary thyroid carcinoma following dendritic cell vaccination.

Cancer Immunol Immunother. 51: 663-668Schott M. Seissler J. Lettmann M. et al.

Immunotherapy for medullary thyroid carcinoma by dendritic cell vaccination.

J Clin Endocrinol Metab. 86: 4965-4969Machens A. Lorenz K. Dralle H.

Time to calcitonin normalization after surgery for node-negative and node-positive medullary thyroid cancer.

J Br Surg. 106: 412-418Van Heerden J. Grant C.S. Gharib H. et al.

Long-term course of patients with persistent hypercalcitoninemia after apparent curative primary surgery for medullary thyroid carcinoma.

Ann Surg. 212: 395Fialkowski E. DeBenedetti M. Moley J.

Long-term outcome of reoperations for medullary thyroid carcinoma.

World J Surg. 32: 754-765Kebebew E. Kikuchi S. Duh Q.Y. et al.

Long-term results of reoperation and localizing studies in patients with persistent or recurrent medullary thyroid cancer.

Arch Surg. 135: 895-901Fromigue J. De Baere T. Baudin E. et al.

Chemoembolization for liver metastases from medullary thyroid carcinoma.

J Clin Endocrinol Metab. 91: 2496-2499Lorenz K. Brauckhoff M. Behrmann C. et al.

Selective arterial chemoembolization for hepatic metastases from medullary thyroid carcinoma.

Surgery. 138: 986-993Koehler V.F. Fuss C.T. Berr C.M. et al.

Medullary thyroid cancer with ectopic Cushing's syndrome: A multicentre case series.

Clin Endocrinol. 96: 847-856Corsello A. RAMUNNO V. Locantore P. et al.

Medullary thyroid cancer with ectopic Cushing’s syndrome: a case report and systematic review of detailed cases from the literature.

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