Current opportunities of comprehensive therapy for bone metastases from thyroid cancer

Background. Approximately 10 % of patients with well-differentiated thyroid cancer (WDTC) develop distant metastases. Of them, only 23 % have bone metastases. Complications associated with metastatic lesion in the skeleton significantly affect overall condition of patients and their quality of life. Surgery and pharmacotherapy are highly traumatic and toxic. Bisphosphonates are stable structural analogues of pyrophosphate that inhibit osteoclast activity, thereby reducing bone resorption, which increases the time to development of bone complications, improves patient’s quality of life, and reduces pain.

The study objective is to assess performance status and pain severity in WDTC patients with distant bone metastases after bisphosphonate therapy.

Materials and methods. We analyzed clinical experience in using bisphosphonates in WDTC patients treated in P.A. Herzen Moscow Oncology Research Institute between 2016 and 2020. This study included 41 patients with WDTC and bone metastases of various locations. Pain severity was evaluated using a 5-point verbal scale; performance status was evaluated using the Eastern Cooperative Oncology Group scale.

Results. We observed an improvement in patients’ performance status (from score 2 to 0 according to the Eastern Cooperative Oncology Group scale) in response to therapy. We also found a decrease in pain intensity (from score 4 to 1.5).

Conclusion. The inclusion of bisphosphonates into the treatment scheme for WDTC patients with bone metastases can reduce pain intensity and improve performance status.

1. Malignant tumors in Russia in 2017 (morbidity and mortality). Ed. by A.D. Kaprin, V.V. Starinsky, G.V. Petrova. Moscow: MNIOI im. P.A. Gertzena, 2018. 250 p. Available at: https://glavonco.ru/cancer_register/Забол_2018_Электр.pdf. (In Russ.).

2. Choksi P., Papaleontiou M., Guo C. et al. Skeletal complications and mortality in thyroid cancer: a population-based study. J Clin Endocrinol Metab 2017;102(4): 1254–60. DOI: 10.1210/jc.2016-3906.

3. Califano I., Deutsch S., Löwenstein A. et al. Outcomes of patients with bone metastases from differentiated thyroid cancer. Arch Endocrinol Metab 2018;62(1):14–20. DOI: 10.20945/2359-3997000000004.

4. Orita Y., Sugitani I., Matsuura M. et al. Prognostic factors and the therapeutic strategy for patients with bone metastasis from differentiated thyroid carcinoma. Surgery 2010;147(3):424–31. DOI: 10.1016/j.surg.2009.10.009.

5. Andrade F., Probstner D., Decnop M. et al. The impact of zoledronic acid and radioactive iodine therapy on morbimortality of patients with bone metastases of thyroid cancer derived from follicular cells. Eur Thyroid J 2019;8(1):46–55. DOI: 10.1159/000493190.

6. Iñiguez-Ariza N.M., Bible K.C., Clarke B.L. Bone metastases in thyroid cancer. J Bone Oncol 2020;21:100282. DOI: 10.1016/j.jbo.2020.100282.

7. Guise T.A., Mundy G.R. Cancer and bone. Endocr Rev 1998;19(1):18–54. DOI: 10.1210/edrv.19.1.0323.

8. Osorio M., Moubayed S.P., Su H., Urken M.L. Systematic review of site distribution of bone metastases in differentiated thyroid cancer. Head Neck 2017;39(4):812–8. DOI: 10.1002/hed.24655.

9. Klein U., von Figura K. Characterization of dermatan sulfate in mucopolysaccharidosis VI. Evidence for the absence of hyaluronidase-like enzymes in human skin fibroblasts. Biochim Biophys Acta 1980;630(1):10–4. DOI: 10.1016/0304-4165(80)90131-2.

10. Grávalos C., Rodríguez C., Sabino A. et al. SEOM Clinical Guideline for bone metastases from solid tumours (2016). Clin Transl Oncol 2016;18(12):1243–53. DOI: 10.1007/s12094-016-1590-1.

11. Harvey H.A., von Reyn Cream L. Biology of bone metastases: causes and consequences. Clin Breast Cancer 2007;7 Suppl 1:S7–13. DOI: 10.3816/cbc.2007.s.001.

12. Russell R.G., Rogers M.J., Frith J.C. et al. The pharmacology of bisphosphonates and new insights into their mechanisms of action. J Bone Miner Res 1999;14 Suppl 2:53–65. DOI: 10.1002/jbmr.5650140212.

13. Frank A.J., Moll J.М., Hort J.F. A comparison of three ways of measuring pain. Rheumatol Rehabil 1982;21(4):211–7. DOI: 10.1093/rheumatology/21.4.211.

14. Al Rahabi M.K., Ghabbani H.M. Clinical impact of bisphosphonates in root canal therapy. Saudi Med J 2018;39(3):232–8. DOI: 10.15537/smj.2018.3.20923.

15. Rosen L.S., Gordon D., Tchekmedyian N.S. et al. Long-term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with nonsmall cell lung carcinoma and other solid tumors. Cancer 2004;100(12):2613–21. DOI: 10.1002/cncr.20308.

16. Andrade F., Probstner D., Decnop M. et al. The impact of zoledronic acid and radioactive iodine therapy on morbimortality of patients with bone metastases of thyroid cancer derived from follicular cells. Eur Thyroid J 2019;8(1):46–55. DOI: 10.1159/000493190.

17. Orita Y., Sugitani I., Takao S. et al. Prospective evaluation of zoledronic acid in the treatment of bone metastases from differentiated thyroid carcinoma. Ann Surg Oncol 2015;22(12):4008–13. DOI: 10.1245/s10434-015-4497-0.