Observation and treatment of patients with progressive metastatic differentiated thyroid cancer after establishment of radioiodine refractoriness

Differentiated thyroid cancer is one of the most common malignant diseases of the endocrine system. Usually, it responds well to the standard treatment (surgery + radioiodine therapy), especially at early stages. During both treatment and dynamic observation, distant metastases are detected in 10–15 % of patients. In these cases, the patients continue treatment with radioactive iodine. If tumor cells have insufficient ability to capture and retain 131I or completely lose this ability, the effect of radioiodine therapy becomes limited and the disease progresses during therapy which leads to 5–10 % decrease in 10-year survival. The main problem in treatment of differentiated thyroid cancer is communication between radiologists in centers performing radioiodine therapy and clinical oncologists performing surgeries and observation at patient’s place of residence. For both specialists, the main goal is to identify clinical situations where early and effective treatment intervention can be beneficial without the risk of overdiagnosis and excessive treatment.

The article considers common questions arising during multidisciplinary interactions with radiologists of radioiodine centers and presents concise guidelines on the observation and treatment procedures for patients with differentiated thyroid cancer.

1. Rumyantsev P.O., Fomin D.K., Rumyantseva U.V. Criteria of well-differentiated thyroid carcinoma resistance to radioiodine therapy. Opukholi golovy i shei = Head and Neck Tumors 2014;(3):4–9. (In Russ.). DOI: 10.17650/2222-1468-2014-0-3-4-9

2. Durante C., Haddy N., Baudin E. et al. Long-term outcome of 444 patients with distant metastases from papillary andfollicular thyroid carcinoma: benefits and limits of radioiodine therapy. J Clin Endocrinol Metab 2006;91(8):2892–9. DOI: 10.1210/jc.2005-2838

3. Eustatia-Rutten C.F., Corssmit E.P., Biermasz N.R. et al. Survival and death causes in differentiated thyroid carcinoma. J Clin Endocrinol Metab 2006;91(1):313–9. DOI: 10.1210/jc.2005-1322

4. Shurinov A.Yu., Borodavina E.V., Krylov V.V. et al. Guidelines for radioiodine therapy in differentiated thyroid cancer and posttherapeutic follow-up. Opukholi golovy i shei = Head and Neck Tumors 2024;14(1):83–95. (In Russ.). DOI: 10.17650/2222-1468-2024-14-1-83-95

5. Choinzonov E.L., Reshetov I.V., Ivanov S.A. et al. Draft of clinical guidelines for the diagnosis and treatment of differentiated thyroid cancer in adult patients. Endokrinnaya khirurgiya = Endocrine Surgery 2022;16(2):5–29. (In Russ.). DOI: 10.14341/serg12792

6. Haugen B., Alexander E., Bible Keith C. et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2016;26(1):1–133. DOI: 10.1089/thy.2015.0020

7. Shurinov A.Yu., Borodavina E.V. Follow-up after radioiodine remnant ablation in differentiated thyroid cancer: the view of nuclear medicine physician. Opukholi golovy i shei = Head and Neck Tumors 2023;13(1):91–101. (In Russ.). DOI: 10.17650/2222-1468-2023-13-1-91-101

8. Biondi B., Cooper D.S. Benefits of thyrotropin suppression versus the risks of adverse effects in differentiated thyroid cancer. Thyroid 2010;20(2):135–46. DOI: 10.1089/thy.2009.0311

9. Eisenhauer E.A., Therasse P., Bogaerts J. et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45(2):228–47. DOI: 10.1016/j.ejca.2008.10.026

10. Bolotina L.V., Vladimirova L.Yu., Dengina N.V. et al. Practical guidelines on drug treatment of head and neck tumors. RUSSCO practical guidelines, part 1. Zlokachestvennie opukholi = Malignant Tumors 2023;13:100–19. (In Russ.).

11. Schlumberger M., Brose M., Elisei R. et al. Definition and management of radioactive iodine-refractory differentiated thyroid cancer. Lancet Diabetes Endocrinol 2014;2(5):356–8. DOI: 10.1016/S2213-8587(13)70215-8

12. Berdelou A., Lamartina L., Klain M. et al. Treatment of refractory thyroid cancer. Endocr Relat Cancer 2018;25(4):R209–23. DOI: 10.1530/ERC-17-0542

13. Tuttle R.M., Brose M.S., Grande E. et al. Novel concepts for initiating multitargeted kinase inhibitors in radioactive iodine refractory differentiated thyroid cancer. Best Pract Res Clin Endocrinol Metab 2017;31(3):295–305.

14. Castagna M.G., Maino F., Cipri C. et al. Delayed risk stratification, to include the response to initial treatment (surgery and radioiodine ablation), has better outcome predictivity in differentiated thyroid cancer patients. Eur J Endocrinol 2011;165(3):441–6. DOI: 10.1530/EJE-11-0466

15. Gruber J.J., Colevas A.D. Differentiated thyroid cancer: focus on emerging treatments for radioactive iodine-refractory patients. Oncologist 2015;20(2):113–26. DOI: 10.1634/theoncologist.2014-0313

16. Durante C., Attard M., Torlontano M. et al. Identification and optimal postsurgical follow-up of patients with very low-risk papillary thyroid microcarcinomas. J Clin Endocrinol Metab 2010;95(11):4882–8. DOI: 10.1210/jc.2010-0762

17. Grani G., Lamartina L., Cantisani V. et al. Interobserver agreement of various thyroid imaging reporting and data systems. Endocr Connect 2018;7(1):1–7. DOI: 10.1530/EC-17-0336

18. Lamartina L., Grani G., Biffoni M. et al. Risk stratification of neck lesions detected sonographically during the follow-up of differentiated thyroid cancer. J Clin Endocrinol Metab 2016;101(8):3036–44. DOI: 10.1210/jc.2016-1440

19. Leenhardt L., Erdogan M.F., Hegedus L. et al. 2013 European Thyroid Association Guidelines for cervical ultrasound scan and ultrasound-guided techniques in the postoperative management of patients with thyroid cancer. Eur Thyroid J 2013;2(3):147–59. DOI: 10.1159/000354537

20. Sgouros G., Kolbert K.S., Sheikh A. et al. Patient-specific dosimetry for 131I thyroid cancer therapy using 124I PET and 3-Dimensional-Internal Dosimetry (3D-ID) software. J Nucl Med 2004;45(8):1366–72.

21. Robbins R.J., Wan Q., Grewal R.K. et al. Real-time prognosis for metastatic thyroid carcinoma based on 2-[18F]fluoro-2-deoxyD-glucose-positron emission tomography scanning. J Clin Endocrinol Metab 2006. DOI: 10.1210/jc.2005-1534

22. Leboulleux S., El Bez I., Borget I. et al. Post-radioiodine treatment whole body scan in the era of fluorodesoxyglucose positron emission tomography for differentiated thyroid carcinoma with elevated serum thyroglobulin levels. Thyroid 2012. DOI: 10.1089/thy.2012-0081

23. NCCN Clinical Practice Guidelines in Oncology Thyroid Carcinoma. Version 4.2023. August 16, 2023. NCCN. Published online 2023. DOI: 10.1001/jamaoncol.2018.2706

24. Taylor M.H., Takahashi S., Capdevila J. et al. Correlation of performance status and neutrophil-lymphocyte ratio with efficacy in radioiodine-refractory differentiated thyroid cancer treated with lenvatinib. Thyroid 2021;31(8):1226–34. DOI: 10.1089/thy.2020.0779

25. Tahara M., Kiyota N., Hoff A.O. et al. Impact of lung metastases on overall survival in the phase 3 SELECT study of lenvatinib in patients with radioiodine-refractory differentiated thyroid cancer. Eur J Cancer 2021;147:51–7. DOI: 10.1016/j.ejca.2020.12.032

26. Brose M.S., Panaseykin Y., Konda B. et al. A randomized study of lenvatinib 18 mg vs 24 mg in patients with radioiodine-refractory differentiated thyroid cancer. J Clin Endocrinol Metab 2022;107(3):776–87. DOI: 10.1210/clinem/dgab731

27. Tahara M., Brose M.S., Wirth L.J. et al. Impact of dose interruption on the efficacy of lenvatinib in a phase 3 study in patients with radioiodine-refractory differentiated thyroid cancer. Eur J Cancer 2019;106:61–8. DOI: 10.1016/j.ejca.2018.10.002