Follow-up after radioiodine remnant ablation in differentiated thyroid cancer: the view of nuclear medicine physician

Timeliness of accurate dynamic observation and a clear understanding of the treatment response guarantees health of patients with differentiated thyroid cancer. Multidimensional approach to evaluation of thyroid-stimulating hormone, tumor markers, ultrasound picture, as well as results of molecular imaging with radioactive iodine is clearly defined in international clinical guidelines. At the A.F. Tsyb Medical Radiological Research Center – branch of the National Medical Research Radiological Center for more than 15 years tactics of control exam 6 months after radioactive iodine ablation has been implemented. The aim of the current article is to consider the sequence of diagnostic search for different responses to treatment of differentiated thyroid cancer.

1. Filetti S., Durante C., Hartl D., Leboulleux S. et al. Berruti on behalf of the ESMO Guidelines Committee. 2019. Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2019;30(12):1856–83. DOI: 10.1093/ annonc/mdz400

2. Клинические рекомендации. Дифференцированный рак щитовидной железы. 2020 г. Доступно по: https://cr.minzdrav.gov. ru/schema/329_1#doc_a1. Clinical recommendations. Differentiated thyroid cancer. 2020 y. Available by: https://cr.minzdrav.gov.ru/schema/329_1#doc_a1. (In Russ.).

3. Gulec S., Ahuja S., Avram A. et al. A joint statement from the American Thyroid Association, the European Association of Nuclear Medicine, the European Thyroid Association, the Society of Nuclear Medicine and Molecular Imaging on Current Diagnostic and Theranostic Approaches in the Management of Thyroid Cancer. Thyroid 2021;31(7):1009–19. DOI: 10.1089/ thy.2020.0826

4. Haddad R., Bischoff L., Ball D. et al. Thyroid Carcinoma. Version 2.2022. NCCN Clinical Practice Guidelines in Oncology. J Nat Compr Canc Netw 2022;20(8):925–51. DOI: 10.6004/ jnccn.2022.0040

5. Шуринов А.Ю., Крылов В.В., Бородавина Е.В. Радиойодаблация при раке щитовидной железы. Исторические и современные аспекты. Обзор литературы. Онкологический журнал: лучевая диагностика, лучевая терапия 2021;4(4):9–19. DOI: 10.37174/2587-7593-2021-4-4-9-19 Shurinov A.Yu., Krylov V.V., Borodavina E.V. Radioiodablation in thyroid cancer. Historical and modern aspects. Literature review. Onkologicheskij zhurnal: luchevaya diagnostika, luchevaya terapiya = Oncological Journal: radiation diagnostics, radiation therapy 2021;4(4):9–19. (In Russ.). DOI: 10.37174/2587-7593- 2021-4-4-9-19

6. Duren M., Siperstein A., Shen W. et al. Value of stimulated serum thyroglobulin levels for detecting persistent or recurrent differentiated thyroid cancer in high- and low-risk patients. Surgery 1999;26(1):13–9. DOI: 10.1067/msy.1999.98849

7. Pacini F., Lippi F., Formica N. et al. Therapeutic doses of iodine-131 reveal undiagnosed metastases in thyroid cancer patients with detectable serum thyroglobulin levels. J Nucl Med 1987;28(12):1888–91.

8. Pineda J., Lee T., Ain K. et al. Iodine-131 therapy for thyroid cancer patients with elevated thyroglobulin and negative diagnostic scan. J Clin Endocrinol Metab 1995;80(5):1488–92. DOI: 10.1210/ jcem.80.5.7744991

9. Roelants V., De Nayer P., Bouckaert A., Beckers C. The predictive value of serum thyroglobulin in the follow-up of differentiated thyroid cancer. Eur J Nucl Med 1997;24:722–7. DOI: 10.1007/ BF00879658

10. Pacini F., Molinaro E., Castagna M. et al. Ablation of thyroid residues with 30 mCi 131I: a comparison in thyroid cancer patients prepared with recombinant human TSH or thyroid hormone withdrawal. J Clin Endocrinol Metab 2002;87(9):4063–8. DOI: 10.1210/jc.2001-011918

11. Kukulska A., Krajewska J., Gawkowska-Suwiriska M. et al. Radioiodine thyroid remnant ablation in patients with differentiated thyroid carcinoma (DTC): prospective comparison of long-term outcomes of treatment with 30, 60, and 100 mCi. Thyroid Res 2010;3(1):9. DOI: 10.1186/1756-6614-3-9

12. Toubeau M., Touzery C., Arveux P. et al. Predictive value for disease progression of serum thyroglobulin levels measured in the postoperative period and after 131I ablation therapy in patients with differentiated thyroid cancer. J Nucl Med 2004;45(6):988–94.

13. Haugen B., Alexander E., Bible K.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

14. Lamartina L., Grani G., Durante C., Filetti S. Recent advances in managing differentiated thyroid cancer. F1000Res 2018;7:86. DOI: 10.12688/f1000research.12811.1

15. Gray J., Singh G., Uttley L., Balasubramanian S. Routine thyroglobulin, neck ultrasound and physical examination in the routine follow up of patients with differentiated thyroid cancer: where is the evidence? Endocrine 2018;62(1):26–33. DOI: 10.1007/ s12020-018-1720-3

16. Prpić M., Franceschi M., Romić M. et al. Thyroglobulin as a tumor marker in differentiated thyroid cancer – clinical considerations. Acta Clin Croat 2018;57(3):518–27. DOI: 10.20471/ acc.2018.57.03.16

17. Giovanella L., Clark P., Chiovato L. et al. Thyroglobulin measurement using highly sensitive assays in patients with differentiated thyroid cancer: a clinical position paper. Eur J Endocrinol 2014;171(2):R33–46. DOI: 10.1530/EJE-14-0148

18. Spencer C. Clinical review: clinical utility of thyroglobulin antibody (TgAb) measurements for patients with differentiated thyroid cancers (DTC). J Clin Endocrinol Metab 2011;96(12):3615–27. DOI: 10.1210/jc.2011-1740

19. Dekker B., Van der Horst-Schrivers A., Brouwers A. et al. Clinical irrelevance of lower titer thyroglobulin autoantibodies in patients with differentiated thyroid carcinoma. Eur Thyroid J 2022 20;11(6):e220137. DOI: 10.1530/ETJ-22-0137

20. Brassard M., Borget I., Edet-Sanson A. et al. Long-term follow-up of patients with papillary and follicular thyroid cancer: a prospective study on 715 patients. J Clin Endocrinol Metab 2011;96(5):1352–9. DOI: 10.1210/jc.2010-2708

21. Durante C., Montesano T., Attard M. et al. Long-term surveillance of papillary thyroid cancer patients who do not undergo postoperative radioiodine remnant ablation: is there a role for serum thyroglobulin measurement? J Clin Endocrinol Metab 2012;97(8):2748–53. DOI: 10.1210/jc.2012-1123

22. Angell T., Spencer C., Rubino B. et al. In search of an unstimulated thyroglobulin baseline value in low-risk papillary thyroid carcinoma patients not receiving radioactive iodine ablation. Thyroid 2014;24(7):1127–33. DOI: 10.1089/thy.2013.0691

23. Grani G., Fumarola A. Thyroglobulin in lymph node fine-needle aspiration washout: a systematic review and meta-analysis of diagnostic accuracy. J Clin Endocrinol Metab 2014;99(6):1970–82. DOI: 10.1210/jc.2014-1098

24. Torlontano M., Attard M., Crocetti U. et al. Follow-up of low risk patients with papillary thyroid cancer: role of neck ultrasonography in detecting lymph node metastases. J Clin Endocrinol Metab 2004;89(7):3402–7. DOI: 10.1210/ jc.2003-031521

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

26. 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

27. Leboulleux S., Girard E., Rose M. et al. Ultrasound criteria of malignancy for cervical lymph nodes in patients followed up for differentiated thyroid cancer. J Clin Endocrinol Metab 2007;92(9):3590–4. DOI: 10.1210/jc.2007-0444

28. Leenhardt L., Erdogan M., 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

29. Lamartina L., Deandreis D., Durante C., Filetti S. ENDOCRINE TUMOURS: imaging in the follow-up of differentiated thyroid cancer: current evidence and future perspectives for a risk-adapted approach. Eur J Endocrinol 2016;175(5):R185–202. DOI: 10.1530/ EJE-16-0088

30. Grani G., Ramundo V., Falcone R. et al. Thyroid cancer patients with no evidence of disease: the need for repeat neck ultrasound. J Clin Endocrinol Metab 2019;104(11):4981–9. DOI: 10.1210/ jc.2019-00962

31. Castagna M., 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

32. Tuttle R., Tala H., Shah J. et al. Estimating risk of recurrence in differentiated thyroid cancer after total thyroidectomy and radioactive iodine remnant ablation: using response to therapy variables to modify the initial risk estimates predicted by the new American Thyroid Association staging system. Thyroid 2010;20(12):1341–9. DOI: 10.1089/thy.2010.0178

33. 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

34. Castagna M., 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

35. Tuttle R., Tala H., Shah J. et al. Estimating risk of recurrence in differentiated thyroid cancer after total thyroidectomy and radioactive iodine remnant ablation: using response to therapy variables to modify the initial risk estimates predicted by the new American Thyroid Association staging system. Thyroid 2010; 20(12):1341–9. DOI: 10.1089/thy.2010.0178

36. Jeon M., Kim W., Park W. et al. Modified dynamic risk stratification for predicting recurrence using the response to initial therapy in patients with differentiated thyroid carcinoma. Eur J Endocrinol 2014;170:23–30. DOI: 10.1530/EJE-13-0524

37. Han J., Kim W., Yim J. et al. Long-term clinical outcome of differentiated thyroid cancer patients with undetectable stimulated thyroglobulin level one year after initial treatment. Thyroid 2012;22(8):784–90. DOI: 10.1089/thy.2011.0322

38. Scheffel R., Zanella A., Antunes D. et al. Low recurrence rates in a cohort of differentiated thyroid carcinoma patients: a referral center experience. Thyroid 2015;25(8):883–9. DOI: 10.1089/ thy.2015.0077

39. Llamas-Olier A., Cuéllar D., Buitrago G. Intermediate-risk papillary thyroid cancer: risk factors for early recurrence in patients with excellent response to initial therapy. Thyroid 2018;28(10):1311–7. DOI: 10.1089/thy.2017.0578

40. Ganly I., Nixon I., Wang L. et al. Survival from differentiated thyroid cancer: what has age got to do with it? Thyroid 2015;25(10):1106–14. DOI: 10.1089/thy.2015.0104

41. Comtois R., Theriault C., Del Vecchio P. Assessment of the efficacy of iodine-131 for thyroid ablation. J Nucl Med 1993;34(11):1927–30.

42. Schlumberger M., Berg G., Cohen O. et al. Follow-up of low-risk patients with differentiated thyroid carcinoma. Eur J Endocrinol 2004;150(2):105–12. DOI: 10.1530/eje.0.1500105

43. Sacks W., Fung C., Chang J. et al. The effectiveness of radioactive iodine for treatment of low-risk thyroid cancer: a systematic analysis of the peer-reviewed literature from 1966 to April 2008. Thyroid 2010;20(11):1235–45. DOI: 10.1089/thy.2009.0455

44. Dietlein M., Eschner W., Grünwald F. et al. Procedure guidelines for radioiodine therapy of differentiated thyroid cancer. Nuklearmedizin 2016;55:77–89. DOI: 10.1055/s-0037-1616478

45. Gastanga M., Cantara S., Pacini F. Reappraisal of the indication for radioiodine thyroid ablation in differentiated thyroid cancer patients. J Endocrinol Invest 2016;39(10):1087–94. DOI: 10.1007/ s40618-016-0503-z

46. Deandreis D., Rubino C., Tala H. et al. Comparison of empiric versus whole-body-blood clearance dosimetry-based approach to radioactive iodine treatment in patients with metastases from differentiated thyroid cancer. J Nucl Med 2017;58(5):717–22. DOI: 10.2967/jnumed.116.179606

47. Verburg F., Schmidt M., Kreissl M. et al. Procedural guideline for Iodine-131 whole-body scintigraphy in differentiated thyroid carcinoma (version 5). Nuklearmedizin 2019;58(3):228–41. DOI: 10.1055/a-0891-1839

48. Giovanella L., Treglia G., Sadeghi R. et al. Unstimulated highly sensitive thyroglobulin in follow-up of differentiated thyroid cancer patients: a meta-analysis. J Clin Endocrinol Metab 2014;99(2):440– 7. DOI: 10.1210/jc.2013-3156

49. Francis G., Waguespack S., Bauer A. et al. American Thyroid Association Guidelines Task Force Management guidelines for children with thyroid nodules and differentiated thyroid cancer. Thyroid 2015;25(7):716–59. DOI: 10.1089/thy.2014.0460

50. Li J., He Z., Bansal V., Hennessey J. Low iodine diet in differentiated thyroid cancer: a review. Clin Endocrinol (Oxf) 2016;84(1):3–12. DOI: 10.1111/cen.12846

51. Campennì А., Barbaro D., Guzzo M. et al. Personalized management of differentiated thyroid cancer in real life – practical guidance from a multidisciplinary panel of experts. Endocrine 2020;70(2):280–91. DOI: 10.1007/s12020-020-02418-x

52. Feine U., Lietzenmayer R., Hanke J. et al. 18FDG whole-body PET in differentiated thyroid carcinoma. Flipflop in uptake patterns of 18FDG and 131I. [In German]. Nuklearmedizin 1995;34(4):127–34.

53. Feine U., Lietzenmayer R., Hanke J. et al. Fluorine-18-FDG and iodine-131-iodide uptake in thyroid cancer. J Nucl Med 1996;37(9):1468–72.

54. Asa S., Aksoy S., Vatankulu B. et al. The role of FDG-PET/CT in differentiated thyroid cancer patients with negative iodine-131 whole-body scan and elevated anti-Tg level. Ann Nucl Med 2014;28(10):970–9. DOI: 10.1007/s12149-014-0897-7

55. Liu Y. The role of 18F-FDG PET/CT in the follow-up of welldifferentiated thyroid cancer with negative thyroglobulin but positive and/or elevated antithyroglobulin antibody. Nucl Med Commun 2016;37(6):577–82. DOI: 10.1097/MNM.0000000000000480

56. Ozkan E., Aras G., Kucuk N. Correlation of 18F-FDG PET/CT findings with histopathological results in differentiated thyroid cancer patients who have increased thyroglobulin or antithyroglobulin antibody levels and negative 131I whole-body scan results. Clin Nucl Med 2013;38(5):326–31. DOI: 10.1097/ RLU.0b013e318286827b

57. Liu M., Cheng L., Jin Y. et al. Predicting 131I-avidity of metastases from differentiated thyroid cancer using 18F-FDG PET/CT in postoperative patients with elevated thyroglobulin. Sci Rep 2018;8(1):4352. DOI: 10.1038/s41598-018-22656-4

58. Silberstein E. The problem of the patient with thyroglobulin elevation but negative iodine scintigraphy: the TENIS syndrome. Semin Nucl Med 2011;41(2):113–20. DOI: 10.1053/j. semnuclmed.2010.10.002

59. Bartel C., Magerefteh S., Avram A. et al. Snmmi procedure standard for scintigraphy for differentiated thyroid cancer. J Nucl Med Technol 2020;48(3):202–9. DOI: 10.2967/jnmt.120.243626

60. Avram А., Giovanella L., Greenspan B. et al. SNMMI procedure standard/eanm practice guideline for nuclear medicine evaluation and therapy of differentiated thyroid cancer: abbreviated version. J Nucl Med 2022;63(6):15N–35N.

61. Petranović P., Kreissl M., Campenni A. et al. SNMMI/EANM practice guideline vs. ETA Consensus Statement: differences and similarities in approaching differentiated thyroid cancer management-the EANM perspective. Eur J Nucl Med Mol Imaging 2022;49(12):3959–63. DOI: 10.1007/s00259-022-05935-1

62. Giovanella L., Treglia G., Ceriani L., Verburg F. Detectable thyroglobulin with negative imaging in differentiated thyroid cancer patients. What to do with negative anatomical imaging and radioiodine scan? Nuklearmedizin 2014;53(1):1–10. DOI: 10.3413/ Nukmed-0618-13-08

63. Van Nostrand D. Radioiodine imaging for differentiated thyroid cancer: not all radioiodine images are performed equally. Thyroid 2019;29(7):901–9.

64. Donohoe K., Aloff J., Avram А. et al. Appropriate use criteria for nuclear medicine in the evaluation and treatment of differentiated thyroid cancer. J Nucl Med 2020;61(3):375–96. DOI: 10.2967/ jnumed.119.240945

65. Binse I., Poeppel T., Ruhlmann M. et al. 68Ga-DOTATOC PET/CT in patients with iodine- and 18F-FDG-negative differentiated thyroid carcinoma and elevated serum thyroglobulin. J Nucl Med 2016;57(10):1512–7. DOI: 10.2967/ jnumed.115.171942

66. Vrachimis A., Stegger L., Wenning C. et al. 68Ga-DOTATATE PET/ MRI and 18F-FDG PET/CT are complementary and superior to diffusion-weighted MR imaging for radioactive-iodine-refractory differentiated thyroid cancer. Eur J Nucl Med Mol Imaging 2016;43(10):1765–72. DOI: 10.1007/s00259-016-3378-5

67. Czepczynski R., Matysiak-Grzes M., Gryczynska M. et al. Peptide receptor radionuclide therapy of differentiated thyroid cancer: efficacy and toxicity. Arch Immunol Ther Exp (Warsz) 2015;63(2):147–54. DOI: 10.1007/s00005-014-0318-6

68. Versari A., Sollini M., Frasoldati A. et al. Differentiated thyroid cancer: A new perspective with radiolabeled somatostatin analogues for imaging and treatment of patients. Thyroid 2014;24(4):715–26. DOI: 10.1089/thy.2013.0225

69. Roll W., Riemann B., Schafers M. et al. 177Lu-DOTATATE therapy in radioiodine-refractory differentiated thyroid cancer: a single center experience. Clin Nucl Med 2018;43(10):e346–51. DOI: 10.1097/RLU.0000000000002219

70. Gubbi S., Koch C., Klubo-Gwiezdzinska J. Peptide receptor radionuclide therapy in thyroid cancer. Front endocrinol (Lausanne) 2022;13:896287. DOI: 10.3389/fendo.2022.896287

71. Ryu Y.J., Lim S.Y., Na Y.M. et al. Prostate-specific membrane antigen expression predicts recurrence of papillary thyroid carcinoma after total thyroidectomy. BMC Cancer 2022;22(1):1278. DOI: 10.1186/s12885-022-10375-z

72. Piek M., De Vries L., Donswijk M. et al. Ploeg IMC. Retrospective analysis of PSMA PET/CT thyroid incidental uptake in adults: incidence, diagnosis, and treatment/outcome in a tertiary cancer referral center and University Medical Center. Eur J Nucl Med Mol Imaging 2022;49(7):2392–400. DOI: 10.1007/s00259- 022-05679-y