Results of treatment of patients with poorly differentiated carcinoma of the thyroid gland

Introduction. Poorly differentiated carcinoma of the thyroid gland (PDTC) is characterised by aggressive, high rate of tumor growth, massive infiltration, early lymphogenous and hematogenous dissemination. Ways to improve treatment outcomes include developing individual treatment programmes. Given the unsatisfactory results of the treatment, the search for combined treatment options is well founded.

Materials and methods. An analysis was made of the treatment of PDTC in patients from May 2014 to July 2021. The study included 24 patients aged 22 to 81 years (9 (37.5 %) men and 15 (62.5 %) women). Surgical treatment was performed in 14 (58.3 %) cases. In 8 (33.3 %) cases, a course of radioiodine therapy with a total dose of 3–4 Gbq was performed in the postoperative period. Seven (29.2 %) patients underwent external beam radiation therapy. In 2 (8.3 %) cases, chemotherapy with carboplatin was performed simultaneously with external beam radiation therapy. Four (16.7 %) patients were prescribed lenvatinib. For one reason or another, 9 (37.5 %) patients did not receive treatment.

Results. For patients not treated, the overall survival rate was 5.8 ± 0.5 months, for patients treated – 9.6 ± 1.0 months (p <0.00095). According to the index Lenvatinib showed a significant increase in the general group of patients – up to 15 months.

Conclusion. Combined treatment in the form of a combination of surgical, radiation and chemotherapeutic methods at PDTC, allows to achieve much higher survival. In order to achieve longer-term stabilization, further research is needed on new ways to enhance the anti-tumor effect of modern drugs.

1. Smallridge R., Ain K., Asa S. et al. American Thyroid Association guidelines for management of patients with anaplastic thyroid cancer. Thyroid 2012;22(11):1104–39. DOI: 10.1089/thy.2012.0302

2. Smallridge R., Copland J. Anaplastic thyroid carcinoma: pathogenesis and emerging therapies. Clin Oncol (R Coll Radiol) 2010;22:486–97. DOI: 10.1016/j.clon.2010.03.013

3. Dijkstra B. Changing patterns of thyroid carcinoma. Ir J Med Sci 2007;176(2):87–90. DOI: 10.1007/s11845-007-0041-y

4. Ranganath R., Shah M., Shah A. Anaplastic thyroid cancer. Curr Opin Endocrinol Diabetes Obes 2015;22(5):387–91. DOI: 10.1097/MED.0000000000000189

5. Sugitani I., Miyauchi A., Sugino K. et al. Prognostic factors and treatment outcomes for anaplastic thyroid carcinoma: ATC Research Consortium of Japan cohort study of 677 patients. World J Surg 2012;36(6):1247–54. DOI: 10.1007/s00268-012-1437-z

6. Sun C., Li Q., Hu Z. et al. Treatment and prognosis of anaplastic thyroid carcinoma: experience from a single institution in China. PLoS One 2013;8:e80011. DOI: 10.1371/journal.pone.0080011

7. Zivaljevic V., Tausanovic K., Paunovic I. et al. Age as a prognostic factor in anaplastic thyroid cancer. Int J Endocrinol 2014;5:240513. DOI: 10.1155/2014/240513

8. Kunstman J., Juhlin C., Goh G. et al. Characterization of the mutational landscape of anaplastic thyroid cancer via whole-exome sequencing. Hum Mol Genet 2015;24(8):2318–29. DOI: 10.1093/hmg/ddu749

9. Landa I., Ibrahimpasic T., Boucai L. et al. Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers. J Clin Invest 2016;126(3):105–66. DOI: 10.1172/JCI85271

10. Latteyer S., Tiedje V., Konig K. et al. Targeted next-generation sequencing for TP53, RAS, BRAF, ALK and NF1 mutations in anaplastic thyroid cancer. Endocrine 2016;54:733–41. DOI: 10.1007/s12020-016-1080-9

11. Tiedje V., Ting S., Herold T. et al. NGS based identification of mutational hotspots for targeted therapy in anaplastic thyroid carcinoma. Oncotarget 2017;8(26):42613–20. DOI: 10.18632/oncotarget.17300

12. Aldinger K. Anaplastic carcinoma of the thyroid. A review of 84 cases of spindle and giant cell carcinoma of the thyroid. Cancer 1978;41(6):2267–75. DOI: 10.1002/1097-0142(197806)41:6<2267::aid-cncr2820410627>3.0.co;2-7

13. Zhang Z. Histone deacetylation of NIS promoter underlies BRAF V600E-promoted NIS silencing in thyroid cancer. Endocr Relat Cancer 2014;21(2):161–73. DOI: 10.1530/ERC-13-0399

14. Lee J., Hwang J., Lee E. Recent progress of genome study for anaplastic thyroid cancer. Genomics Inform 2013;11(2):68–75. DOI: 10.5808/GI.2013.11.2.68

15. Howell G., Hodak S., Yip L. RAS mutations in thyroid cancer. Oncologist 2013;18)8):926–32. DOI: 10.1634/theoncologist.2013-0072

16. Garcia-Rostan G., Camp R., Herrero A. et al. β-Catenin dysregulation in thyroid neoplasms. Am J Pathol 2001;158(3): 987–96. DOI: 10.1016/s0002-9440(10)64045-x

17. Sastre-Perona A., Santisteban P. Role of the Wnt pathway in thyroid cancer. Front Endocrinol (Lausanne) 2012;3:31.

18. Brauner E., Gunda V., Vanden Borre P. et al. Combining BRAF inhibitor and anti PD-L1 antibody dramatically improves tumor regression and anti tumor immunity in an immunocompetent murine model of anaplastic thyroid cancer. Oncotarget 2016;7(13):17194–211. DOI: 10.18632/oncotarget.7839

19. Haymart M., Banerjee M., Yin H. et at. Marginal treatment benefit in anaplastic thyroid cancer. Cancer 2013;119(17):3133–9. DOI: 10.1002/cncr.28187

20. Orita Y., Sugitani I., Amemiya T., Fujimoto Y. Prospective application of our novel prognostic index in the treatment of anaplastic thyroid carcinoma. Surgery 2011;150(6):1212–9. DOI: 10.1016/j.surg.2011.09.005

21. Wendler J., Kroiss M., Gast K. et al. Clinical presentation, treatment and outcome of anaplastic thyroid carcinoma: results of a multicenter study in Germany. Eur J Endocrinol 2016;175(6):521–9. DOI: 10.1530/EJE-16-0574

22. Sun C., Li C., Hu Z. et al. Influence of risk grouping on therapeutic decisions in patients with anaplastic thyroid carcinoma. Eur Arch Otorhinolaryngol 2015;272(4):985–93. DOI: 10.1007/s00405-014-2937-2

23. Steggink L., van Dijk B., Links T., Plukker J. Survival in anaplastic thyroid cancer in relation to pre-existing goiter: a population-based study. Am J Surg 2015;209(6):1013–19. DOI: 10.1016/j.amjsurg.2014.06.027

24. Dralle H., Musholt T., Schabram J. et al. German Association of Endocrine Surgeons practice guideline for the surgical management of malignant thyroid tumors. Langenbecks Arch Surg 2013;398(3):347–75. DOI: 10.1007/s00423-013-1057-6

25. Goffredo P., Thomas S., Adam M. et al. Impact of timeliness of resection and thyroidectomy margin status on survival for patients with anaplastic thyroid cancer: an analysis of 335 cases. Ann Surg Oncol 2015;22(13):4166–74. DOI: 10.1245/s10434-015-4742-6

26. Brignardello E., Palestini N., Felicetti F. et al. Early surgery and survival of patients with anaplastic thyroid carcinoma: analysis of a case series referred to a single institution between 1999 and 2012. Thyroid 2014;24(11):1600–6. DOI: 10.1089/thy.2014.0004

27. Pezzi T., Mohamed A., Sheu T. et al. Radiation therapy dose is associated with improved survival for unresected anaplastic thyroid carcinoma: outcomes from the National Cancer Data Base. Cancer 2017;123(9):1653–61. DOI: 10.1002/cncr.30493

28. Dumke A., Pelz T., Vordermark D. Long-term results of radiotherapy in anaplastic thyroid cancer. Radiat Oncol 2014;9(1):90. DOI: 10.1186/1748-717X-9-90

29. Lowe N., Loughran S., Slevin N., Yap B. Anaplastic thyroid cancer: the addition of systemic chemotherapy to radiotherapy led to an observed improvement in survival – a single centre experience and review of the literature. Sci World J 2014;2014:674583. DOI: 10.1155/2014/674583

30. Higashiyama T., Ito Y., Hirokawa M. et al. Induction chemotherapy with weekly paclitaxel administration for anaplastic thyroid carcinoma. Thyroid 2010;20(1):7–14. DOI: 10.1089/thy.2009.0115

31. Sosa J., Elisei R., Jarzab B. et al. Randomized safety and efficacy study of fosbretabulin with paclitaxel/carboplatin against anaplastic thyroid carcinoma. Thyroid 2014;24(2):232–40. DOI: 10.1089/thy.2013.0078

32. Marten K., Gudena V. Use of vemurafenib in anaplastic thyroid carcinoma: a case report. Cancer Biol Ther 2015;16(10):1430–3. DOI: 10.1080/15384047.2015.1071734

33. Savvides P. Phase II trial of sorafenib in patients with advanced anaplastic carcinoma of the thyroid. Thyroid 2013;23(5):600–4. DOI: 10.1089/thy.2012.0103

34. Subbiah V., Kreitman R., Wainberg Z. et al. Dabrafenib and trametinib treatment in patients with locally advanced or metastatic BRAF V600-mutant anaplastic thyroid cancer. J Clin Oncol 2017;36(1):7–13. DOI: 10.1200/JCO.2017.73.6785

35. Tahara M., Kiyota N., Yamazaki T. et al. Lenvatinib for anaplastic thyroid cancer. Front Oncol 2017;7:25. DOI:10.3389/fonc.2017.00025