Current status and perspectives of neoadjuvant therapy for locally advanced thyroid cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHANG Yu ,  WANG Yu

Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, P. R. China;

Corresponding author：

WANG Yu, Email: neck130@sina.com

Keywords：

locally advanced thyroid cancer; neoadjuvant therapy; radical resection; tyrosine kinase inhibitor; immunotherapy

DOI：

10.7507/1007-9424.202410054

Video：

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[Abstract] Patients with locally advanced thyroid cancer often face challenges in achieving radical surgery during initial diagnosis. This has become a significant hurdle in the treatment of thyroid cancer. With the continuous development of systemic therapy for thyroid cancer, several studies have demonstrated that neoadjuvant therapy can shrink tumors in some patients, thereby increasing the chances of complete resection and improving prognosis. Targeted therapy plays a crucial role as a core component of neoadjuvant treatment. Simultaneously, the potential efficacy of immunotherapy has gained attention, showing promising prospects. We aim to summarize the research progress and existing issues regarding neoadjuvant therapy for locally advanced thyroid cancer. We look forward to more high-quality clinical studies providing robust evidence for neoadjuvant therapy in locally advanced thyroid cancer, expanding the breadth of treatment options.

1.	Raffaelli M, Voloudakis N, Barczynski M, et al. European Society of Endocrine Surgeons (ESES) consensus statement on advanced thyroid cancer: definitions and management. Br J Surg, 2024, 111(8): znae199.
2.	Hamidi S, Dadu R, Zafereo ME, et al. Initial management of BRAF V600E-variant anaplastic thyroid cancer: the FAST Multidisciplinary Group Consensus Statement. JAMA Oncol, 2024, 10(9): 1264-1271.
3.	中国医师协会外科医师分会甲状腺外科医师委员会, 中国研究型医院学会甲状腺疾病专业委员会, 中国医疗保健国际交流促进会普通外科学分会, 等. 局部进展期甲状腺癌新辅助治疗中国专家共识 (2023版). 中国实用外科杂志, 2023, 43(8): 841-848.
4.	Pitoia F, Abelleira E, Román-González A, et al. Neoadjuvant treatment of locally advanced thyroid cancer: a preliminary Latin American experience. Thyroid, 2024, 34(7): 949-952.
5.	Russell M, Gild ML, Wirth LJ, et al. Neoadjuvant therapy to improve resectability of advanced thyroid cancer: a real-world experience. Head Neck, 2024 Mar 15.
6.	Cabanillas ME, Schlumberger M, Jarzab B, et al. A phase 2 trial of lenvatinib (E7080) in advanced, progressive, radioiodine-refractory, differentiated thyroid cancer: a clinical outcomes and biomarker assessment. Cancer, 2015, 121(16): 2749-2756.
7.	Schlumberger M, Tahara M, Wirth LJ, et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med, 2015, 372(7): 621-630.
8.	Maurer E, Eilsberger F, Wächter S, et al. Mutation-based, short-term “neoadjuvant” treatment allows resectability in stage ⅣB and C anaplastic thyroid cancer. Eur Arch Otorhinolaryngol, 2023, 280(3): 1509-1518.
9.	Kim M, Ahn J, Song DE, et al. Real-world experience of lenvatinib in patients with advanced anaplastic thyroid cancer. Endocrine, 2021, 71(2): 427-433.
10.	Gay S, Monti E, Trambaiolo Antonelli C, et al. Case report: lenvatinib in neoadjuvant setting in a patient affected by invasive poorly differentiated thyroid carcinoma. Future Oncol, 2019, 15(24s): 13-19.
11.	Alshehri K, Alqurashi Y, Merdad M, et al. Neoadjuvant lenvatinib for inoperable thyroid cancer: a case report and literature review. Cancer Rep (Hoboken), 2022, 5(2): e1466.
12.	Qian K, Wang Y, An N, et al. Effect and safety of apatinib as neoadjuvant therapy in locally advanced differentiated thyroid cancer: a phase 2 trial. J Endocr Soc, 2024, 8(9): bvae132.
13.	Huang NS, Wei WJ, Xiang J, 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(12): 1808-1813.
14.	Brose MS, Nutting CM, Jarzab B, et al. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet, 2014, 384(9940): 319-328.
15.	Cleary JM, Sadow PM, Randolph GW, et al. Neoadjuvant treatment of unresectable medullary thyroid cancer with sunitinib. J Clin Oncol, 2010, 28(23): e390-e392.
16.	Subbiah V, Kreitman RJ, Wainberg ZA, et al. Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: the phase 2 ROAR trial. Nat Med, 2023, 29(5): 1103-1112.
17.	Subbiah V, Kreitman RJ, Wainberg ZA, 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(4): 406-415.
18.	Wang JR, Zafereo ME, Dadu R, et al. Complete surgical resection following neoadjuvant dabrafenib plus trametinib in BRAFV600E-mutated anaplastic thyroid carcinoma. Thyroid, 2019, 29(8): 1036-1043.
19.	Haddad RI, Bischoff L, Ball D, et al. Thyroid carcinoma, version 2. 2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw, 2022, 20(8): 925-951.
20.	Zhao X, Wang JR, Dadu R, et al. Surgery after BRAF-directed therapy is associated with improved survival in BRAFV600E mutant anaplastic thyroid cancer: a single-center retrospective cohort study. Thyroid, 2023, 33(4): 484-491.
21.	Yun KM, Cohen EEW. An era of advances in systemic therapies for advanced thyroid cancer. JCO Oncol Pract, 2024, 20(7): 899-906.
22.	Boucai L, Zafereo M, Cabanillas ME. Thyroid cancer: a review. JAMA, 2024, 331(5): 425-435.
23.	Subbiah V, Hu MI, Wirth LJ, 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(8): 491-501.
24.	Huang NS, Chen JY, Meng Y, et al. Pralsetinib as neoadjuvant therapy for RET-Altered differentiated thyroid cancer: two case reports. Oral Oncol, 2024 Sep 21: 159: 107014.
25.	Capdevila J, Wirth LJ, Ernst T, et al. PD-1 blockade in anaplastic thyroid carcinoma. J Clin Oncol, 2020, 38(23): 2620-2627.
26.	Hamidi S, Iyer PC, Dadu R, et al. Checkpoint inhibition in addition to dabrafenib/trametinib for BRAFV600E-mutated anaplastic thyroid carcinoma. Thyroid, 2024, 34(3): 336-346.
27.	Barbaro D, Forleo R, Profilo MA, et al. Neoadjuvant treatment with lenvatinib and pembrolizumab in a BRAF V600E-mutated anaplastic thyroid cancer: a case report. Front Endocrinol (Lausanne), 2024 Jul 9: 15: 1389294.
28.	Chen JY, Huang NS, Wei WJ, 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(12): 7172-7180.
29.	Onoda N, Sugino K, Higashiyama T, et al. The safety and efficacy of weekly paclitaxel administration for anaplastic thyroid cancer patients: a nationwide prospective study. Thyroid, 2016, 26(9): 1293-1299.
30.	Yamazaki H, Sugino K, Katoh R, et al. Response to neoadjuvant paclitaxel predicts survival in anaplastic thyroid carcinoma. Cancer Med, 2023, 12(3): 3027-3035.
31.	Huang NS, Li Q, Gao XY, et al. Using a CT-based scale to evaluate disease extension and the resectability of locally advanced thyroid cancer. Eur Radiol, 2023, 33(12): 9063-9073.
32.	Haugen BR, Alexander EK, Bible KC, 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): 1-133.
33.	Wang J, Takashima S, Matsushita T, et al. Esophageal invasion by thyroid carcinomas: prediction using magnetic resonance imaging. J Comput Assist Tomogr, 2003, 27(1): 18-25.

1. Raffaelli M, Voloudakis N, Barczynski M, et al. European Society of Endocrine Surgeons (ESES) consensus statement on advanced thyroid cancer: definitions and management. Br J Surg, 2024, 111(8): znae199.
2. Hamidi S, Dadu R, Zafereo ME, et al. Initial management of BRAF V600E-variant anaplastic thyroid cancer: the FAST Multidisciplinary Group Consensus Statement. JAMA Oncol, 2024, 10(9): 1264-1271.
3. 中国医师协会外科医师分会甲状腺外科医师委员会, 中国研究型医院学会甲状腺疾病专业委员会, 中国医疗保健国际交流促进会普通外科学分会, 等. 局部进展期甲状腺癌新辅助治疗中国专家共识 (2023版). 中国实用外科杂志, 2023, 43(8): 841-848.
4. Pitoia F, Abelleira E, Román-González A, et al. Neoadjuvant treatment of locally advanced thyroid cancer: a preliminary Latin American experience. Thyroid, 2024, 34(7): 949-952.
5. Russell M, Gild ML, Wirth LJ, et al. Neoadjuvant therapy to improve resectability of advanced thyroid cancer: a real-world experience. Head Neck, 2024 Mar 15.
6. Cabanillas ME, Schlumberger M, Jarzab B, et al. A phase 2 trial of lenvatinib (E7080) in advanced, progressive, radioiodine-refractory, differentiated thyroid cancer: a clinical outcomes and biomarker assessment. Cancer, 2015, 121(16): 2749-2756.
7. Schlumberger M, Tahara M, Wirth LJ, et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med, 2015, 372(7): 621-630.
8. Maurer E, Eilsberger F, Wächter S, et al. Mutation-based, short-term “neoadjuvant” treatment allows resectability in stage ⅣB and C anaplastic thyroid cancer. Eur Arch Otorhinolaryngol, 2023, 280(3): 1509-1518.
9. Kim M, Ahn J, Song DE, et al. Real-world experience of lenvatinib in patients with advanced anaplastic thyroid cancer. Endocrine, 2021, 71(2): 427-433.
10. Gay S, Monti E, Trambaiolo Antonelli C, et al. Case report: lenvatinib in neoadjuvant setting in a patient affected by invasive poorly differentiated thyroid carcinoma. Future Oncol, 2019, 15(24s): 13-19.
11. Alshehri K, Alqurashi Y, Merdad M, et al. Neoadjuvant lenvatinib for inoperable thyroid cancer: a case report and literature review. Cancer Rep (Hoboken), 2022, 5(2): e1466.
12. Qian K, Wang Y, An N, et al. Effect and safety of apatinib as neoadjuvant therapy in locally advanced differentiated thyroid cancer: a phase 2 trial. J Endocr Soc, 2024, 8(9): bvae132.
13. Huang NS, Wei WJ, Xiang J, 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(12): 1808-1813.
14. Brose MS, Nutting CM, Jarzab B, et al. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet, 2014, 384(9940): 319-328.
15. Cleary JM, Sadow PM, Randolph GW, et al. Neoadjuvant treatment of unresectable medullary thyroid cancer with sunitinib. J Clin Oncol, 2010, 28(23): e390-e392.
16. Subbiah V, Kreitman RJ, Wainberg ZA, et al. Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: the phase 2 ROAR trial. Nat Med, 2023, 29(5): 1103-1112.
17. Subbiah V, Kreitman RJ, Wainberg ZA, 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(4): 406-415.
18. Wang JR, Zafereo ME, Dadu R, et al. Complete surgical resection following neoadjuvant dabrafenib plus trametinib in BRAFV600E-mutated anaplastic thyroid carcinoma. Thyroid, 2019, 29(8): 1036-1043.
19. Haddad RI, Bischoff L, Ball D, et al. Thyroid carcinoma, version 2. 2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw, 2022, 20(8): 925-951.
20. Zhao X, Wang JR, Dadu R, et al. Surgery after BRAF-directed therapy is associated with improved survival in BRAFV600E mutant anaplastic thyroid cancer: a single-center retrospective cohort study. Thyroid, 2023, 33(4): 484-491.
21. Yun KM, Cohen EEW. An era of advances in systemic therapies for advanced thyroid cancer. JCO Oncol Pract, 2024, 20(7): 899-906.
22. Boucai L, Zafereo M, Cabanillas ME. Thyroid cancer: a review. JAMA, 2024, 331(5): 425-435.
23. Subbiah V, Hu MI, Wirth LJ, 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(8): 491-501.
24. Huang NS, Chen JY, Meng Y, et al. Pralsetinib as neoadjuvant therapy for RET-Altered differentiated thyroid cancer: two case reports. Oral Oncol, 2024 Sep 21: 159: 107014.
25. Capdevila J, Wirth LJ, Ernst T, et al. PD-1 blockade in anaplastic thyroid carcinoma. J Clin Oncol, 2020, 38(23): 2620-2627.
26. Hamidi S, Iyer PC, Dadu R, et al. Checkpoint inhibition in addition to dabrafenib/trametinib for BRAFV600E-mutated anaplastic thyroid carcinoma. Thyroid, 2024, 34(3): 336-346.
27. Barbaro D, Forleo R, Profilo MA, et al. Neoadjuvant treatment with lenvatinib and pembrolizumab in a BRAF V600E-mutated anaplastic thyroid cancer: a case report. Front Endocrinol (Lausanne), 2024 Jul 9: 15: 1389294.
28. Chen JY, Huang NS, Wei WJ, 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(12): 7172-7180.
29. Onoda N, Sugino K, Higashiyama T, et al. The safety and efficacy of weekly paclitaxel administration for anaplastic thyroid cancer patients: a nationwide prospective study. Thyroid, 2016, 26(9): 1293-1299.
30. Yamazaki H, Sugino K, Katoh R, et al. Response to neoadjuvant paclitaxel predicts survival in anaplastic thyroid carcinoma. Cancer Med, 2023, 12(3): 3027-3035.
31. Huang NS, Li Q, Gao XY, et al. Using a CT-based scale to evaluate disease extension and the resectability of locally advanced thyroid cancer. Eur Radiol, 2023, 33(12): 9063-9073.
32. Haugen BR, Alexander EK, Bible KC, 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): 1-133.
33. Wang J, Takashima S, Matsushita T, et al. Esophageal invasion by thyroid carcinomas: prediction using magnetic resonance imaging. J Comput Assist Tomogr, 2003, 27(1): 18-25.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

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