CC BY 4.0 · World J Nucl Med
DOI: 10.1055/s-0044-1787731
Original Article

Predictive Factors of Radioactive Iodine Therapy Refractoriness in Patients with Differentiated Thyroid Carcinoma

1   Department of Nuclear Medicine, Academic Hospital Ibn Sina, Faculty of Medicine and Pharmacy, University Mohammed V, Souissi, Rabat, Morocco
,
1   Department of Nuclear Medicine, Academic Hospital Ibn Sina, Faculty of Medicine and Pharmacy, University Mohammed V, Souissi, Rabat, Morocco
,
Mourad Zekri
1   Department of Nuclear Medicine, Academic Hospital Ibn Sina, Faculty of Medicine and Pharmacy, University Mohammed V, Souissi, Rabat, Morocco
,
Dounia Alami
1   Department of Nuclear Medicine, Academic Hospital Ibn Sina, Faculty of Medicine and Pharmacy, University Mohammed V, Souissi, Rabat, Morocco
,
Hamza Zarouf
1   Department of Nuclear Medicine, Academic Hospital Ibn Sina, Faculty of Medicine and Pharmacy, University Mohammed V, Souissi, Rabat, Morocco
,
Imad Ghfir
1   Department of Nuclear Medicine, Academic Hospital Ibn Sina, Faculty of Medicine and Pharmacy, University Mohammed V, Souissi, Rabat, Morocco
,
Hasnae Guerrouj
1   Department of Nuclear Medicine, Academic Hospital Ibn Sina, Faculty of Medicine and Pharmacy, University Mohammed V, Souissi, Rabat, Morocco
› Author Affiliations

Abstract

Aim Differentiated thyroid carcinoma (DTC) is the most prevalent endocrine malignancy, with radioactive iodine (RAI) therapy being a standard of care. However, RAI refractoriness, occurring in a subset of patients, significantly impacts survival rates. Understanding predictive factors for RAI refractoriness is crucial for optimizing patient management.

Methods This retrospective study analyzed data from 90 DTC patients at Ibn Sina University Hospital, Morocco. Patients were categorized into RAI-refractory (RAIR) and non-RAIR groups based on established criteria. Statistical analyses, including univariate and multivariate logistic regression, were performed to identify predictive factors of RAI refractoriness.

Results Age at the time of diagnosis ≥ 54 years, primary tumor diameter ≥ 29 mm, and distal/nodal metastasis were independent predictors of RAIR-DTC. Additionally, the oncocytic carcinoma histological subtype significantly increased the risk of refractoriness. These findings were consistent with previous studies and underscored the importance of early detection and risk stratification.

Conclusion Recognition of predictive factors for RAI refractoriness, including age, tumor size, distal/nodal metastasis, and histological subtype, facilitates early identification of high-risk patients. This enables timely intervention and personalized treatment strategies, particularly relevant in resource-limited settings. Further prospective studies are warranted to validate these findings and explore additional molecular markers for improved prediction of RAI refractoriness.



Publication History

Article published online:
14 June 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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  • References

  • 1 Chai J, Zhang R, Zheng W. et al. Predictive value of clinical and pathological characteristics for metastatic radioactive iodine-refractory differentiated thyroid carcinoma: a 16-year retrospective study. Front Endocrinol (Lausanne) 2022; 13: 930180
  • 2 Jung CK, Bychkov A, Kakudo K. Update from the 2022 World Health Organization Classification of Thyroid Tumors: a standardized diagnostic approach. Endocrinol Metab (Seoul) 2022; 37 (05) 703-718
  • 3 Zhang D, Tang J, Kong D. et al. Impact of gender and age on the prognosis of differentiated thyroid carcinoma: a retrospective analysis based on SEER. Horm Cancer 2018; 9 (05) 361-370
  • 4 Sobin LH, Gospodarowicz MK, Wittekind C. TNM Classification of Malignant Tumours. Hoboken, NJ: John Wiley & Sons; 2011
  • 5 Al-Ibraheem A, Al-Rasheed U, Mashhadani N. et al. Long-term survival analysis and prognostic factors of Arabic patients with differentiated thyroid carcinoma: a 20-year observational study at the King Hussein Cancer Center (KHCC) involving 528 patients. Cancers (Basel) 2023; 15 (16) 4102
  • 6 Tang J, Kong D, Cui Q. et al. Racial disparities of differentiated thyroid carcinoma: clinical behavior, treatments, and long-term outcomes. World J Surg Oncol 2018; 16 (01) 45
  • 7 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 (01) 1-133
  • 8 Cooper DS, Doherty GM, Haugen BR. et al; American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009; 19 (11) 1167-1214
  • 9 Worden F. Treatment strategies for radioactive iodine-refractory differentiated thyroid cancer. Ther Adv Med Oncol 2014; 6 (06) 267-279
  • 10 Xing M, Haugen BR, Schlumberger M. Progress in molecular-based management of differentiated thyroid cancer. Lancet 2013; 381 (9871) 1058-1069
  • 11 Wang W, Larson SM, Fazzari M. et al. Prognostic value of [18F]fluorodeoxyglucose positron emission tomographic scanning in patients with thyroid cancer. J Clin Endocrinol Metab 2000; 85 (03) 1107-1113
  • 12 Karapanou O, Simeakis G, Vlassopoulou B, Alevizaki M, Saltiki K. Advanced RAI-refractory thyroid cancer: an update on treatment perspectives. Endocr Relat Cancer 2022; 29 (05) R57-R66
  • 13 Liu J, Liu Y, Lin Y. Jun Liang radioactive iodine-refractory differentiated thyroid cancer and redifferentiation therapy. Endocrinol Metab (Seoul) 2019; 34 (03) 215-225
  • 14 Iravani A, Solomon B, Pattison DA. et al. Mitogen-activated protein kinase pathway inhibition for redifferentiation of radioiodine refractory differentiated thyroid cancer: an evolving protocol. Thyroid 2019; 29 (11) 1634-1645
  • 15 Karapanou O, Simeakis G, Vlassopoulou B, Alevizaki M, Saltiki K. Advanced RAI-refractory thyroid cancer: an update on treatment perspectives. Endocr Relat Cancer 2022; 29 (05) R57-R66 DOI: 10.1530/ERC-22-0006.
  • 16 Tuttle RM, Ahuja S, Avram AM. et al. Controversies, consensus, and collaboration in the use of 131I therapy in differentiated thyroid cancer: a joint statement from the American Thyroid Association, the European Association of Nuclear Medicine, the Society of Nuclear Medicine and Molecular Imaging, and the European Thyroid Association. Thyroid 2019; 29 (04) 461-470
  • 17 Mu ZZ, Zhang X, Lin YS. Identification of radioactive iodine refractory differentiated thyroid cancer. Chonnam Med J 2019; 55 (03) 127-135
  • 18 Wierts R, Brans B, Havekes B. et al. Dose-response relationship in differentiated thyroid cancer patients undergoing radioiodine treatment assessed by means of 124I PET/CT. J Nucl Med 2016; 57 (07) 1027-1032
  • 19 Chen P, Feng HJ, Ouyang W. et al. Risk factors for nonremission and progression-free survival after I-131 therapy in patients with lung metastasis from differentiated thyroid cancer: a single institute, retrospective analysis in Southern China. Endocr Pract 2016; 22 (09) 1048-1056
  • 20 Schneider DF, Chen H. New developments in the diagnosis and treatment of thyroid cancer. CA Cancer J Clin 2013; 63 (06) 374-394
  • 21 Liu Y, Wang Y, Zhang W. Scoring system and a simple nomogram for predicting radioiodine refractory differentiated thyroid cancer: a retrospective study. EJNMMI Res 2022; 12 (01) 45
  • 22 Li G, Lei J, Song L. et al. Radioiodine refractoriness score: a multivariable prediction model for postoperative radioiodine-refractory differentiated thyroid carcinomas. Cancer Med 2018; 7 (11) 5448-5456
  • 23 Kersting D, Seifert R, Kessler L. et al. Predictive factors for RAI-refractory disease and short overall survival in PDTC. Cancers (Basel) 2021; 13 (07) 1728
  • 24 Nakanishi K, Kikumori T, Miyajima N. et al. Impact of patient age and histological type on radioactive iodine avidity of recurrent lesions of differentiated thyroid carcinoma. Clin Nucl Med 2018; 43 (07) 482-485
  • 25 Wei S, Gao M, Zhao C. et al. Low expression of sodium iodide symporter expression in aggressive variants of papillary thyroid carcinoma. Int J Clin Oncol 2014; 19 (05) 800-804
  • 26 Faggiano A, Coulot J, Bellon N. et al. Age-dependent variation of follicular size and expression of iodine transporters in human thyroid tissue. J Nucl Med 2004; 45 (02) 232-237
  • 27 Mihailovic J, Stefanovic L, Malesevic M, Markoski B. The importance of age over radioiodine avidity as a prognostic factor in differentiated thyroid carcinoma with distant metastases. Thyroid 2009; 19 (03) 227-232
  • 28 Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 2010; 17 (06) 1471-1474
  • 29 Liu L, Shi Y, Lai Q. et al. Construction of a signature model to predict the radioactive iodine response of papillary thyroid cancer. Front Endocrinol (Lausanne) 2022; 13: 865909
  • 30 Lee F, Kuo C-Y, Tsai C-H, Cheng S-P. Propensity score-matched analysis to identify pathways associated with loss of sodium iodide symporter in papillary thyroid cancer. Curr Issues Mol Biol 2022; 44 (04) 1488-1496
  • 31 Tavares C, Coelho MJ, Eloy C. et al. NIS expression in thyroid tumors, relation with prognosis clinicopathological and molecular features. Endocr Connect 2018; 7 (01) 78-90
  • 32 Luo Y, Jiang H, Xu W. et al. Clinical, pathological, and molecular characteristics correlating to the occurrence of radioiodine refractory differentiated thyroid carcinoma: a systematic review and meta-analysis. Front Oncol 2020; 10: 549882
  • 33 Kim HJ, Lee JI, Kim NK, Min Y-K, Kim SW, Chung JH. Prognostic implications of radioiodine avidity and serum thyroglobulin in differentiated thyroid carcinoma with distant metastasis. World J Surg 2013; 37 (12) 2845-2852
  • 34 Besic N, Vidergar-Kralj B, Frkovic-Grazio S, Movrin-Stanovnik T, Auersperg M. The role of radioactive iodine in the treatment of Hürthle cell carcinoma of the thyroid. Thyroid 2003; 13 (06) 577-584
  • 35 Ghossein RA, Hiltzik DH, Carlson DL. et al. Prognostic factors of recurrence in encapsulated Hurthle cell carcinoma of the thyroid gland: a clinicopathologic study of 50 cases. Cancer 2006; 106 (08) 1669-1676
  • 36 Bonichon F, Schvartz C, Toubeau M. et al. Hurthle cell thyroid carcinoma: a multicentric retrospective study of 130 patients. Thyroid 2012; 1: A100
  • 37 Watson RG, Brennan MD, Goellner JR, van Heerden JA, McConahey WM, Taylor WF. Invasive Hürthle cell carcinoma of the thyroid: natural history and management. Mayo Clin Proc 1984; 59 (12) 851-855
  • 38 Sugino K, Ito K, Mimura T, Kameyama K, Iwasaki H, Ito K. Hürthle cell tumor of the thyroid: analysis of 188 cases. World J Surg 2001; 25 (09) 1160-1163
  • 39 McDonald MP, Sanders LE, Silverman ML, Chan HS, Buyske J. Hürthle cell carcinoma of the thyroid gland: prognostic factors and results of surgical treatment. Surgery 1996; 120 (06) 1000-1004 , discussion 1004–1005
  • 40 Cooper DS, Schneyer CR. Follicular and Hürthle cell carcinoma of the thyroid. Endocrinol Metab Clin North Am 1990; 19 (03) 577-591
  • 41 Ganly I, Ricarte Filho J, Eng S. et al. Genomic dissection of Hurthle cell carcinoma reveals a unique class of thyroid malignancy. J Clin Endocrinol Metab 2013; 98 (05) E962-E972
  • 42 Simões-Pereira J, Mourinho N, Ferreira TC, Limbert E, Cavaco BM, Leite V. Avidity and outcomes of radioiodine therapy for distant metastasis of distinct types of differentiated thyroid cancer. J Clin Endocrinol Metab 2021; 106 (10) e3911-e3922
  • 43 Nixon IJ, Whitcher MM, Palmer FL. et al. The impact of distant metastases at presentation on prognosis in patients with differentiated carcinoma of the thyroid gland. Thyroid 2012; 22 (09) 884-889
  • 44 Lakshmanan A, Scarberry D, Shen DH, Jhiang SM. Modulation of sodium iodide symporter in thyroid cancer. Horm Cancer 2014; 5 (06) 363-373
  • 45 Schlumberger M, Brose M, Elisei R. et al. Definition and management of radioactive iodine-refractory differentiated thyroid cancer. Lancet Diabetes Endocrinol 2014; 2 (05) 356-358
  • 46 Kogai T, Brent GA. The sodium iodide symporter (NIS): regulation and approaches to targeting for cancer therapeutics. Pharmacol Ther 2012; 135 (03) 355-370
  • 47 Aashiq M, Silverman DA, Na'ara S, Takahashi H, Amit M. Radioiodine-refractory thyroid cancer: molecular basis of redifferentiation therapies, management, and novel therapies. Cancers (Basel) 2019; 11 (09) 1382
  • 48 Azouzi N, Cailloux J, Cazarin JM. et al. NADPH oxidase NOX4 is a critical mediator of BRAFV600E-induced downregulation of the sodium/iodide symporter in papillary thyroid carcinomas. Antioxid Redox Signal 2017; 26 (15) 864-877
  • 49 García B, Santisteban P. PI3K is involved in the IGF-I inhibition of TSH-induced sodium/iodide symporter gene expression. Mol Endocrinol 2002; 16 (02) 342-352
  • 50 Crezee T, Tesselaar MH, Jaeger M. et al. IGF2 is a potential factor in RAI-refractory differentiated thyroid cancer. Oncol Lett 2021; 22 (02) 590