Table Info

Table 3.

Main adverse events classified according to the Common Terminology Criteria Adverse Events associated with MKIs and HS-TKIs treatment

Drug	Hypertension		Diarrhea		Skin rash		Anorexia		Nausea		Weight loss		Fatigue		QTc prolongation
Drug	Any grade	G3/4	Any gade	G3/4	Any grade	G3/4	Any grade	G3/4	Any grade	G3/4	Any grade	G3/4	Any grade	G3/4	Any grade	G3/4
Lenvatinib [5]	+++	++	+++	+	+	+	+++	+	++	+	++	+	+++	+	+	+
Sorafenib [6]	++	+	+++	+	+++	+	++	+	+	NE	++	+	++	+	NE	NE
Cabozantinib [36]	++	+	+++	+	+	+	++	+	++	+	++	+	++	+	NE	NE
Selpercatinib [41]	++	+	+++	+	+	+	+	+	+	+	+	+	+	+	NE	NE
Vandetanib [35]	++	+	+++	+	++	+	+	+	++	NE	+	NE	+	+	+	+
Pralsetinib [82]	+	+	+	+	NE	NE	NE	NE	NE	NE	NE	NE	+	+	NE	NE
Entrectinib [58]	NE	NE	++	+	+	NE	NE	NE	+	NE	NE	NE	++	+	NE	NE
Larotrectinib [13]	NE	NE	++	+	NE	NE	NE	NE	++	+	NE	NE	++	+	NE	NE
Dabrafenib + Trametinib [22]	+	+	+	NE	+	NE	+	NE	+++	+	NE	NE	+++	+	NE	NE

MKIs: multikinase inhibitors; HS-TKIs: highly selective tyrosine kinase inhibitors; QTc: QT interval corrected for heart rate; NE: no evidence; +: < 25%; ++: 25–50%; +++: 50–75%; ++++: > 75%

Declarations

Author contributions

LV and AM: Conceptualization, Data curation, Investigation, Methodology, Writing—original draft, Writing—review & editing. Both authors read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

References

Cabanillas ME, Ryder M, Jimenez C. Targeted Therapy for Advanced Thyroid Cancer: Kinase Inhibitors and Beyond. Endocr Rev. 2019;40:1573–604. [DOI] [PubMed] [PMC]

Matrone A, Valerio L, Pieruzzi L, Giani C, Cappagli V, Lorusso L, et al. Protein kinase inhibitors for the treatment of advanced and progressive radiorefractory thyroid tumors: From the clinical trials to the real life. Best Pract Res Clin Endocrinol Metab. 2017;31:319–34. [DOI] [PubMed]

Valerio L, Pieruzzi L, Giani C, Agate L, Bottici V, Lorusso L, et al. Targeted Therapy in Thyroid Cancer: State of the Art. Clin Oncol (R Coll Radiol). 2017;29:316–24. [DOI] [PubMed]

Ark N, Zemo S, Nolen D, Holsinger FC, Weber RS. Management of locally invasive well-differentiated thyroid cancer. Surg Oncol Clin N Am. 2008;17:145–55, ix. [DOI] [PubMed]

Schlumberger M, Tahara M, Wirth LJ, Robinson B, Brose MS, Elisei R, et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med. 2015;372:621–30. [DOI] [PubMed]

Brose MS, Nutting CM, Jarzab B, Elisei R, Siena S, Bastholt L, et al.; DECISION investigators. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet. 2014;384:319–28. [DOI] [PubMed] [PMC]

Brose MS, Robinson BG, Sherman SI, Jarzab B, Lin CC, Vaisman F, et al. Cabozantinib for previously treated radioiodine-refractory differentiated thyroid cancer: Updated results from the phase 3 COSMIC-311 trial. Cancer. 2022;128:4203–12. [DOI] [PubMed] [PMC]

Filetti S, Durante C, Hartl DM, Leboulleux S, Locati LD, Newbold K, et al.; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. ESMO Clinical Practice Guideline update on the use of systemic therapy in advanced thyroid cancer. Ann Oncol. 2022;33:674–84. [DOI] [PubMed]

Subbiah V, Wolf J, Konda B, Kang H, Spira A, Weiss J, et al. Tumour-agnostic efficacy and safety of selpercatinib in patients with RET fusion-positive solid tumours other than lung or thyroid tumours (LIBRETTO-001): a phase 1/2, open-label, basket trial. Lancet Oncol. 2022;23:1261–73. [DOI] [PubMed] [PMC]

10.

Chu YH, Dias-Santagata D, Farahani AA, Boyraz B, Faquin WC, Nosé V, et al. Clinicopathologic and molecular characterization of NTRK-rearranged thyroid carcinoma (NRTC). Mod Pathol. 2020;33:2186–97. [DOI] [PubMed] [PMC]

11.

Hong DS, DuBois SG, Kummar S, Farago AF, Albert CM, Rohrberg KS, et al. Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials. Lancet Oncol. 2020;21:531–40. [DOI] [PubMed] [PMC]

12.

Laetsch TW, DuBois SG, Mascarenhas L, Turpin B, Federman N, Albert CM, et al. Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions: phase 1 results from a multicentre, open-label, phase 1/2 study. Lancet Oncol. 2018;19:705–14. [DOI] [PubMed] [PMC]

13.

Drilon A, Laetsch TW, Kummar S, DuBois SG, Lassen UN, Demetri GD, et al. Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children. N Engl J Med. 2018;378:731–9. [DOI] [PubMed] [PMC]

14.

Al-Salama ZT, Keam SJ. Entrectinib: First Global Approval. Drugs. 2019;79:1477–83. [DOI] [PubMed]

15.

Germani MM, Boccaccio C, Matrone A, Molinaro E, Alì G, Giordano M, et al. A Misleading Case of NTRK-Rearranged Papillary Thyroid Carcinoma. Oncologist. 2024;29:84–8. [DOI] [PubMed] [PMC]

16.

Willis C, Au T, Hejazi A, Griswold C, Schabath MB, Thompson J, et al. Clinical characteristics and treatment patterns of patients with NTRK fusion-positive solid tumors: A multisite cohort study at US academic cancer centers. J Manag Care Spec Pharm. 2024;30:672–83. [DOI] [PubMed] [PMC]

17.

Chawla N, Bui NQ, Seetharam M. Evolving role of entrectinib in treatment of NTRK-positive tumors. Future Oncol. 2021;17:2835–46. [DOI] [PubMed]

18.

Ricarte-Filho JC, Halada S, O’Neill A, Casado-Medrano V, Laetsch TW, Franco AT, et al. The clinical aspect of NTRK-fusions in pediatric papillary thyroid cancer. Cancer Genet. 2022;262–263:57–63. [DOI] [PubMed] [PMC]

19.

Scott LJ. Larotrectinib: First Global Approval. Drugs. 2019;79:201–6. [DOI] [PubMed]

20.

Peng X, Lei J, Li Z, Zhang K. Case report: Visibly curative effect of dabrafenib and trametinib on advanced thyroid carcinoma in 2 patients. Front Oncol. 2023;12:1099268. [DOI] [PubMed] [PMC]

21.

Jafri S, Yaqub A. Redifferentiation of BRAF V600E-Mutated Radioiodine Refractory Metastatic Papillary Thyroid Cancer After Treatment With Dabrafenib and Trametinib. Cureus. 2021;13:e17488. [DOI] [PubMed] [PMC]

22.

Leboulleux S, Do Cao C, Zerdoud S, Attard M, Bournaud C, Lacroix L, et al. A Phase II Redifferentiation Trial with Dabrafenib-Trametinib and 131I in Metastatic Radioactive Iodine Refractory BRAF p.V600E-Mutated Differentiated Thyroid Cancer. Clin Cancer Res. 2023;29:2401–9. [DOI] [PubMed]

23.

Dierks C, Seufert J, Aumann K, Ruf J, Klein C, Kiefer S, et al. Combination of Lenvatinib and Pembrolizumab Is an Effective Treatment Option for Anaplastic and Poorly Differentiated Thyroid Carcinoma. Thyroid. 2021;31:1076–85. [DOI] [PubMed] [PMC]

24.

Filetti S, Durante C, Hartl D, Leboulleux S, Locati LD, Newbold K, et al. Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-updagger. Ann Oncol. 2019;30:1856–83. [DOI] [PubMed]

25.

Luongo C, Porcelli T, Sessa F, De Stefano MA, Scavuzzo F, Damiano V, et al. Combination of Lenvatinib and Pembrolizumab as Salvage Treatment for Paucicellular Variant of Anaplastic Thyroid Cancer: A Case Report. Curr Oncol. 2021;28:5401–7. [DOI] [PubMed] [PMC]

26.

Boudin L, Morvan JB, Thariat J, Métivier D, Marcy PY, Delarbre D. Rationale Efficacy and Safety Evidence of Lenvatinib and Pembrolizumab Association in Anaplastic Thyroid Carcinoma. Curr Oncol. 2022;29:7718–31. [DOI] [PubMed] [PMC]

27.

Maurer E, Eilsberger F, Wächter S, Riera Knorrenschild J, Pehl A, Holzer K, et al. Mutation-based, short-term “neoadjuvant” treatment allows resectability in stage IVB and C anaplastic thyroid cancer. Eur Arch Otorhinolaryngol. 2023;280:1509–18. [DOI] [PubMed] [PMC]

28.

Locati LD, Colombo E, Dedecjus M, de la Fouchardière C, Sents W, Bongiovanni M, et al. Current picture of anaplastic thyroid cancer patients’ care and meetable needs: A survey of 94 Institutions from the EORTC Endocrine and Head and Neck Cancer Groups. Eur J Cancer. 2023;180:146–54. [DOI] [PubMed]

29.

Bible KC, Kebebew E, Brierley J, Brito JP, Cabanillas ME, Clark TJ Jr, et al. 2021 American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer. Thyroid. 2021;31:337–86. [DOI] [PubMed] [PMC]

30.

Subbiah V, Kreitman RJ, Wainberg ZA, Cho JY, Schellens JHM, Soria JC, et al. Dabrafenib plus trametinib in patients with BRAF V600E-mutant anaplastic thyroid cancer: updated analysis from the phase II ROAR basket study. Ann Oncol. 2022;33:406–15. [DOI] [PubMed] [PMC]

31.

Iyer PC, Cote GJ, Hai T, Gule-Monroe M, Bui-Griffith J, Williams MD, et al. Circulating BRAF V600E Cell-Free DNA as a Biomarker in the Management of Anaplastic Thyroid Carcinoma. JCO Precis Oncol. 2018;2:PO.18.00173. [DOI] [PubMed] [PMC]

32.

Bueno F, Smulever A, Califano I, Guerra J, Del Grecco A, Carrera JM, et al. Dabrafenib plus trametinib treatment in patients with anaplastic thyroid carcinoma: an Argentinian experience. Endocrine. 2023;80:134–41. [DOI] [PubMed] [PMC]

33.

Waguespack SG, Drilon A, Lin JJ, Brose MS, McDermott R, Almubarak M, et al. Efficacy and safety of larotrectinib in patients with TRK fusion-positive thyroid carcinoma. Eur J Endocrinol. 2022;186:631–43. [DOI] [PubMed] [PMC]

34.

Damásio I, Simões-Pereira J, Donato S, Horta M, Cavaco BM, Rito M, et al. Entrectinib in the neoadjuvant setting of anaplastic thyroid cancer: a case report. Eur Thyroid J. 2022;12:e220179. [DOI] [PubMed] [PMC]

35.

Wells SA Jr, Robinson BG, Gagel RF, Dralle H, Fagin JA, Santoro M, et al. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol. 2012;30:134–41. [DOI] [PubMed] [PMC]

36.

Elisei R, Schlumberger MJ, Müller SP, Schöffski P, Brose MS, Shah MH, et al. Cabozantinib in progressive medullary thyroid cancer. J Clin Oncol. 2013;31:3639–46. [DOI] [PubMed] [PMC]

37.

Schlumberger M, Jarzab B, Cabanillas ME, Robinson B, Pacini F, Ball DW, et al. A Phase II Trial of the Multitargeted Tyrosine Kinase Inhibitor Lenvatinib (E7080) in Advanced Medullary Thyroid Cancer. Clin Cancer Res. 2016;22:44–53. [DOI] [PubMed]

38.

Matrone A, Prete A, Nervo A, Ragni A, Agate L, Molinaro E, et al. Lenvatinib as a salvage therapy for advanced metastatic medullary thyroid cancer. J Endocrinol Invest. 2021;44:2139–51. [DOI] [PubMed]

39.

Wirth LJ, Sherman E, Robinson B, Solomon B, Kang H, Lorch J, et al. Efficacy of Selpercatinib in RET-Altered Thyroid Cancers. N Engl J Med. 2020;383:825–35. [DOI] [PubMed] [PMC]

40.

Wirth LJ, Brose MS, Subbiah V, Worden F, Solomon B, Robinson B, et al. Durability of Response With Selpercatinib in Patients With RET-Activated Thyroid Cancer: Long-Term Safety and Efficacy From LIBRETTO-001. J Clin Oncol. 2024;42:3187–95. [DOI] [PubMed] [PMC]

41.

Hadoux J, Elisei R, Brose MS, Hoff AO, Robinson BG, Gao M, et al.; LIBRETTO-531 Trial Investigators. Phase 3 Trial of Selpercatinib in Advanced RET-Mutant Medullary Thyroid Cancer. N Engl J Med. 2023;389:1851–61. [DOI] [PubMed]

42.

Subbiah V, Hu MI, Wirth LJ, Schuler M, Mansfield AS, Curigliano G, et al. Pralsetinib for patients with advanced or metastatic RET-altered thyroid cancer (ARROW): a multi-cohort, open-label, registrational, phase 1/2 study. Lancet Diabetes Endocrinol. 2021;9:491–501. [DOI] [PubMed]

43.

Subbiah V, Hu MI, Mansfield AS, Taylor MH, Schuler M, Zhu VW, et al. Pralsetinib in Patients with Advanced/Metastatic Rearranged During Transfection (RET)-Altered Thyroid Cancer: Updated Efficacy and Safety Data from the ARROW Study. Thyroid. 2024;34:26–40. [DOI] [PubMed]

44.

Rao SN, Smallridge RC. Anaplastic thyroid cancer: An update. Best Pract Res Clin Endocrinol Metab. 2023;37:101678. [DOI] [PubMed]

45.

Maniakas A, Zafereo M, Cabanillas ME. Anaplastic Thyroid Cancer: New Horizons and Challenges. Endocrinol Metab Clin North Am. 2022;51:391–401. [DOI] [PubMed]

46.

Hamidi S, Dadu R, Zafereo ME, Ferrarotto R, Wang JR, Maniakas A, et al. Initial Management of BRAF V600E-Variant Anaplastic Thyroid Cancer: The FAST Multidisciplinary Group Consensus Statement. JAMA Oncol. 2024;10:1264–71. [DOI] [PubMed]

47.

Yang SR, Tsai MH, Hung CJ, Peng SL, Chiu NT, Huang YH, et al. Anaplastic Thyroid Cancer Successfully Treated With Radiation and Immunotherapy: A Case Report. AACE Clin Case Rep. 2021;7:299–302. [DOI] [PubMed] [PMC]

48.

Romei C, Tacito A, Molinaro E, Piaggi P, Cappagli V, Pieruzzi L, et al. Clinical, pathological and genetic features of anaplastic and poorly differentiated thyroid cancer: A single institute experience. Oncol Lett. 2018;15:9174–82. [DOI] [PubMed] [PMC]

49.

Pozdeyev N, Gay LM, Sokol ES, Hartmaier R, Deaver KE, Davis S, et al. Genetic Analysis of 779 Advanced Differentiated and Anaplastic Thyroid Cancers. Clin Cancer Res. 2018;24:3059–68. [DOI] [PubMed] [PMC]

50.

Quiros RM, Ding HG, Gattuso P, Prinz RA, Xu X. Evidence that one subset of anaplastic thyroid carcinomas are derived from papillary carcinomas due to BRAF and p53 mutations. Cancer. 2005;103:2261–8. [DOI] [PubMed]

51.

Minna E, Brich S, Todoerti K, Pilotti S, Collini P, Bonaldi E, et al. Cancer Associated Fibroblasts and Senescent Thyroid Cells in the Invasive Front of Thyroid Carcinoma. Cancers (Basel). 2020;12:112. [DOI] [PubMed] [PMC]

52.

Wang JR, Zafereo ME, Dadu R, Ferrarotto R, Busaidy NL, Lu C, et al. Complete Surgical Resection Following Neoadjuvant Dabrafenib Plus Trametinib in BRAFV600E-Mutated Anaplastic Thyroid Carcinoma. Thyroid. 2019;29:1036–43. [DOI] [PubMed] [PMC]

53.

McIver B, Hay ID, Giuffrida DF, Dvorak CE, Grant CS, Thompson GB, et al. Anaplastic thyroid carcinoma: a 50-year experience at a single institution. Surgery. 2001;130:1028–34. [DOI] [PubMed]

54.

Navas Moreno V, Sebastián Valles F, Lahera Vargas M, Hernández Marín B, Carrillo López E, Marazuela M, et al. Neoadjuvant Treatment in Locally Advanced Thyroid Carcinoma. J Clin Med. 2024;13:5769. [DOI] [PubMed] [PMC]

55.

Barbaro D, Forleo R, Profilo MA, Lapi P, Giani C, Torregrossa L, et al. Neoadjuvant treatment with lenvatinib and pembrolizumab in a BRAF V600E-mutated anaplastic thyroid cancer: a case report. Front Endocrinol (Lausanne). 2024;15:1389294. [DOI] [PubMed] [PMC]

56.

Zhao X, Wang JR, Dadu R, Busaidy NL, Xu L, Learned KO, et al. Surgery After BRAF-Directed Therapy Is Associated with Improved Survival in BRAF^V600EMutant Anaplastic Thyroid Cancer: A Single-Center Retrospective Cohort Study. Thyroid. 2023;33:484–91. [DOI] [PubMed] [PMC]

57.

Cabanillas ME, Ferrarotto R, Garden AS, Ahmed S, Busaidy NL, Dadu R, et al. Neoadjuvant BRAF- and Immune-Directed Therapy for Anaplastic Thyroid Carcinoma. Thyroid. 2018;28:945–51. [DOI] [PubMed] [PMC]

58.

Song Y, Zhang Y, Bai Y, Wang T, Xu G, Ma X, et al. Combination kinase inhibitors and immunotherapy for unresectable anaplastic thyroid carcinoma: A retrospective single-center study. Oral Oncol. 2024;159:107067. [DOI] [PubMed]

59.

Doebele RC, Drilon A, Paz-Ares L, Siena S, Shaw AT, Farago AF, et al.; trial investigators. Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1-2 trials. Lancet Oncol. 2020;21:271–82. [DOI] [PubMed] [PMC]

60.

US Department of Health and Human Services. Common terminology criteria for adverse events (CTCAE) v5. 0. Cancer Ther Eval Progr. 2017;155.

61.

Barbaro D, Lapi P, Viacava P, Torregrossa L. Low-intermediate dose of lenvatinib in anaplastic thyroid cancer is highly effective and safe. BMJ Case Rep. 2020;13:e236934. [DOI] [PubMed] [PMC]

62.

Iwasaki H, Toda S, Suganuma N, Murayama D, Nakayama H, Masudo K. Lenvatinib vs. palliative therapy for stage IVC anaplastic thyroid cancer. Mol Clin Oncol. 2020;12:138–43. [DOI] [PubMed] [PMC]

63.

Huang J, Xu B, Mo H, Zhang W, Chen X, Wu D, et al. Safety, Activity, and Biomarkers of SHR-1210, an Anti-PD-1 Antibody, for Patients with Advanced Esophageal Carcinoma. Clin Cancer Res. 2018;24:1296–304. [DOI] [PubMed]

64.

Yang S, Ji D, Xue F, Chen T, Wang Y, Ji Q. Neoadjuvant famitinib and camrelizumab, a new combined therapy allowing surgical resection of the primary site for anaplastic thyroid carcinoma. Cancer Rep (Hoboken). 2023;6:e1770. [DOI] [PubMed] [PMC]

65.

Molinaro E, Campopiano MC, Pieruzzi L, Matrone A, Agate L, Bottici V, et al. Active Surveillance in Papillary Thyroid Microcarcinomas is Feasible and Safe: Experience at a Single Italian Center. J Clin Endocrinol Metab. 2020;105:e172–80. [DOI] [PubMed] [PMC]

66.

Tuttle RM, Fagin JA, Minkowitz G, Wong RJ, Roman B, Patel S, et al. Natural History and Tumor Volume Kinetics of Papillary Thyroid Cancers During Active Surveillance. JAMA Otolaryngol Head Neck Surg. 2017;143:1015–20. [DOI] [PubMed] [PMC]

67.

Sanabria A, Ferraz C, Ku CHC, Padovani R, Palacios K, Paz JL, et al. Implementing active surveillance for low-risk thyroid carcinoma into clinical practice: collaborative recommendations for Latin America. Arch Endocrinol Metab. 2024;68:e230371. [DOI] [PubMed] [PMC]

68.

Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26:1–133. [DOI] [PubMed] [PMC]

69.

Tuttle RM, Ahuja S, Avram AM, Bernet VJ, Bourguet P, Daniels GH, et al. Controversies, Consensus, and Collaboration in the Use of ¹³¹I Therapy in Differentiated Thyroid Cancer: A Joint Statement from the American Thyroid Association, the European Association of Nuclear Medicine, the Society of Nuclear Medicine and Molecular Imaging, and the European Thyroid Association. Thyroid. 2019;29:461–70. [DOI] [PubMed]

70.

Gay S, Monti E, Trambaiolo Antonelli C, Mora M, Spina B, Ansaldo G, et al. Case report: lenvatinib in neoadjuvant setting in a patient affected by invasive poorly differentiated thyroid carcinoma. Future Oncol. 2019;15:13–9. [DOI] [PubMed]

71.

Alshehri K, Alqurashi Y, Merdad M, Samargandy S, Daghistani R, Marzouki H. Neoadjuvant lenvatinib for inoperable thyroid cancer: A case report and literature review. Cancer Rep (Hoboken). 2022;5:e1466. [DOI] [PubMed] [PMC]

72.

Valerio L, Giani C, Agate L, Molinaro E, Viola D, Bottici V, et al. Prevalence and Risk Factors of Developing Fistula or Organ Perforation in Patients Treated with Lenvatinib for Radioiodine-Refractory Thyroid Cancer. Eur Thyroid J. 2021;10:399–407. [DOI] [PubMed] [PMC]

73.

Pitoia F, Abelleira E, Román-González A, Danilovic DLS, Scheffel RS, Maia AL, et al. Neoadjuvant Treatment of Locally Advanced Thyroid Cancer: A Preliminary Latin American Experience. Thyroid. 2024;34:949–52. [DOI] [PubMed]

74.

Tsuboi M, Takizawa H, Aoyama M, Tangoku A. Surgical treatment of locally advanced papillary thyroid carcinoma after response to lenvatinib: A case report. Int J Surg Case Rep. 2017;41:89–92. [DOI] [PubMed] [PMC]

75.

Stewart KE, Strachan MWJ, Srinivasan D, MacNeill M, Wall L, Nixon IJ. Tyrosine Kinase Inhibitor Therapy in Locally Advanced Differentiated Thyroid Cancer: A Case Report. Eur Thyroid J. 2019;8:102–7. [DOI] [PubMed] [PMC]

76.

Iwasaki H, Toda S, Ito H, Nemoto D, Murayama D, Okubo Y, et al. A Case of Unresectable Papillary Thyroid Carcinoma Treated with Lenvatinib as Neoadjuvant Chemotherapy. Case Rep Endocrinol. 2020;2020:6438352. [DOI] [PubMed] [PMC]

77.

Danilovic DLS, Castro G Jr, Roitberg FSR, Vanderlei FAB, Bonani FA, Freitas RMC, et al. Potential role of sorafenib as neoadjuvant therapy in unresectable papillary thyroid cancer. Arch Endocrinol Metab. 2018;62:370–5. [DOI] [PubMed] [PMC]

78.

Nava CF, Scheffel RS, Cristo AP, Ferreira CV, Weber S, Zanella AB, et al. Neoadjuvant Multikinase Inhibitor in Patients With Locally Advanced Unresectable Thyroid Carcinoma. Front Endocrinol (Lausanne). 2019;10:712. [DOI] [PubMed] [PMC]

79.

Huang NS, Wei WJ, Xiang J, Chen JY, Guan Q, Lu ZW, et al. The Efficacy and Safety of Anlotinib in Neoadjuvant Treatment of Locally Advanced Thyroid Cancer: A Single-Arm Phase II Clinical Trial. Thyroid. 2021;31:1808–13. [DOI] [PubMed]

80.

Chen JY, Huang NS, Wei WJ, Hu JQ, Cao YM, Shen Q, et al. The Efficacy and Safety of Surufatinib Combined with Anti PD-1 Antibody Toripalimab in Neoadjuvant Treatment of Locally Advanced Differentiated Thyroid Cancer: A Phase II Study. Ann Surg Oncol. 2023;30:7172–80. [DOI] [PubMed]

81.

Matrone A, Gambale C, Prete A, Cappagli V, Lorusso L, Bottici V, et al. Systemic treatment of advanced, metastatic, medullary thyroid carcinoma. J Cancer Metastasis Treat. 2021;7:23. [DOI]

82.

Wells SA Jr, Asa SL, Dralle H, Elisei R, Evans DB, Gagel RF, et al.; American Thyroid Association Guidelines Task Force on Medullary Thyroid Carcinoma. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015;25:567–610. [DOI] [PubMed] [PMC]

83.

Matrone A, Gambale C, Prete A, Elisei R. Sporadic Medullary Thyroid Carcinoma: Towards a Precision Medicine. Front Endocrinol (Lausanne). 2022;13:864253. [DOI] [PubMed] [PMC]

84.

Ciampi R, Ramone T, Romei C, Casalini R, Matrone A, Prete A, et al. NF1 Gene Inactivation Acts as Tumor Driver in RET/RAS Negative Medullary Thyroid Carcinomas. Eur J Endocrinol. 2023:lvad051. [DOI] [PubMed]

85.

Ciampi R, Romei C, Ramone T, Prete A, Tacito A, Cappagli V, et al. Genetic Landscape of Somatic Mutations in a Large Cohort of Sporadic Medullary Thyroid Carcinomas Studied by Next-Generation Targeted Sequencing. iScience. 2019;20:324–36. [DOI] [PubMed] [PMC]

86.

Romei C, Tacito A, Molinaro E, Agate L, Bottici V, Viola D, et al. Twenty years of lesson learning: how does the RET genetic screening test impact the clinical management of medullary thyroid cancer? Clin Endocrinol (Oxf). 2015;82:892–9. [DOI] [PubMed]

87.

Matrone A, Elisei R. Insights into highly selective RET inhibitors in medullary thyroid cancer. Curr Opin Endocr Metab Res. 2024;35:100521. [DOI]

88.

Romei C, Casella F, Tacito A, Bottici V, Valerio L, Viola D, et al. New insights in the molecular signature of advanced medullary thyroid cancer: evidence of a bad outcome of cases with double RET mutations. J Med Genet. 2016;53:729–34. [DOI] [PubMed]

89.

Zhang Y, Zheng WH, Zhou SH, Gu JL, Yu Q, Zhu YZ, et al. Molecular genetics, therapeutics and RET inhibitor resistance for medullary thyroid carcinoma and future perspectives. Cell Commun Signal. 2024;22:460. [DOI] [PubMed] [PMC]

90.

Adashek JJ, Desai AP, Andreev-Drakhlin AY, Roszik J, Cote GJ, Subbiah V. Hallmarks of RET and Co-occuring Genomic Alterations in RET-aberrant Cancers. Mol Cancer Ther. 2021;20:1769–76. [DOI] [PubMed] [PMC]

91.

Gigliotti BJ, Brooks JA, Wirth LJ. Fundamentals and recent advances in the evaluation and management of medullary thyroid carcinoma. Mol Cell Endocrinol. 2024;592:112295. [DOI] [PubMed]

92.

Jozaghi Y, Zafereo M, Williams MD, Gule-Monroe MK, Wang J, Grubbs EG, et al. Neoadjuvant selpercatinib for advanced medullary thyroid cancer. Head Neck. 2021;43:E7–12. [DOI] [PubMed] [PMC]

93.

Contrera KJ, Gule-Monroe MK, Hu MI, Cabanillas ME, Busaidy NL, Dadu R, et al. Neoadjuvant Selective RET Inhibitor for Medullary Thyroid Cancer: A Case Series. Thyroid. 2023;33:129–32. [DOI] [PubMed]

94.

De Leo S, Trevisan M, Re Sartò GV, Moneta C, Pirovano M, Colombo C, et al. Letter to the Editor: Tumor Lysis Syndrome During Selpercatinib Treatment in a Patient with Medullary Thyroid Cancer. Thyroid. 2023;33:1130–2. [DOI] [PubMed]

95.

Grasic Kuhar C, Lozar T, Besic N, Music Marolt M. Outcome of Patients with Locally Advanced Metastatic Medullary Thyroid Cancer and Induction Therapy with Tyrosine Kinase Inhibitors in Slovenia. Adv Ther. 2021;38:5684–99. [DOI] [PubMed]

96.

Cleary JM, Sadow PM, Randolph GW, Palmer EL, Lynch TP, Nikiforov YE, et al. Neoadjuvant treatment of unresectable medullary thyroid cancer with sunitinib. J Clin Oncol. 2010;28:e390–2. [DOI] [PubMed]

97.

Golingan H, Hunis B, Golding AC, Bimston DN, Harrell RM. Neoadjuvant Lenvatinib in Advanced Unresectable Medullary Thyroid Carcinoma: A Case Report. AACE Clin Case Rep. 2019;6:e73–8. [DOI] [PubMed] [PMC]

98.

Gugenheim J, Crovetto A, Petrucciani N. Neoadjuvant therapy for pancreatic cancer. Updates Surg. 2022;74:35–42. [DOI] [PubMed] [PMC]

99.

Korde LA, Somerfield MR, Carey LA, Crews JR, Denduluri N, Hwang ES, et al. Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breast Cancer: ASCO Guideline. J Clin Oncol. 2021;39:1485–505. [DOI] [PubMed] [PMC]

100.

Smith HG, Nilsson PJ, Shogan BD, Harji D, Gambacorta MA, Romano A, et al. Neoadjuvant treatment of colorectal cancer: comprehensive review. BJS Open. 2024;8:zrae038. [DOI] [PubMed] [PMC]

101.

Matrone A, De Napoli L, Torregrossa L, Aghababyan A, Papini P, Ambrosini CE, et al. Core Needle Biopsy Can Early and Precisely Identify Large Thyroid Masses. Front Oncol. 2022;12:854755. [DOI] [PubMed] [PMC]

102.

Clifton-Bligh RJ. Mechanisms of resistance to RET-directed therapies. Endocr Relat Cancer. 2025;32:e240224. [DOI] [PubMed] [PMC]

103.

Subbiah V, Gouda MA, Iorgulescu JB, Dadu R, Patel K, Sherman S, et al. Adaptive Darwinian off-target resistance mechanisms to selective RET inhibition in RET driven cancer. NPJ Precis Oncol. 2024;8:62. [DOI] [PubMed] [PMC]