Abstract
Most common thyroid cancers are differentiated thyroid cancers (DTCs) and have papillary, follicular, or Hürthle cell morphology. Papillary thyroid carcinoma (PTC) is the most common malignant tumor of the thyroid gland. The incidence of DTC increases with age. While most of the patients with DTC have an excellent prognosis, the outcome can be poor when diagnosed in elderly patients.
Purpose of Review
Current treatment approach for DTC includes surgery, thyroid-stimulating hormone (TSH) suppression, radioactive iodine, external beam radiotherapy, or systemic treatments such as kinase inhibitors. Radioactive iodine therapy (RAI) is the primary first-line systemic treatment for advanced DTC. However, during the course of treatment, the tumor may become refractory to RAI. Elderly patients are more likely to be diagnosed with advanced disease that can be refractory to RAI.
Recent Findings
The advent of TKIs (tyrosine kinase inhibitors) and their usage in RAI refractory disease has shown improved progression-free survival. These agents are, however, associated with increased toxicity.
Summary
The variable nature of disease and toxicity associated with the systemic therapy makes it important to have an individualized approach to management, especially in the elderly population who can be more susceptible to toxicities.
Similar content being viewed by others
References
Papers of particular interest, published recently, have been highlighted as: • Of importance
Lim H, Devesa SS, Sosa JA, Check D, Kitahara CM. Trends in thyroid cancer incidence and mortality in the United States, 1974–2013. JAMA. 2017;317:1338–48.
Ahn HS, Kim HJ, Welch HG. Korea's thyroid-cancer “epidemic”--screening and overdiagnosis. N Engl J Med. 2014;371(19):1765–7. https://doi.org/10.1056/NEJMp1409841.
Furuya-Kanamori L, Bell KJ, Clark J, Glasziou P, Doi SA. Prevalence of differentiated thyroid cancer in autopsy studies Over six decades: a meta-analysis. J Clin Oncol. 2016.
Greene FL, Trotti A, Fritz AG, et al. Thyroid. In: Greene FL, Trotti A, Fritz AG, Compton CC, Byrd DR, Edge SB, editors. AJCC cancer staging handbook. 7th ed. Chicago: American Joint Committee on Cancer; 2010. p. 111–22.
Shteinshnaider M, Muallem Kalmovich L, Koren S, Or K, Cantrell D, Benbassat C. Reassessment of differentiated thyroid cancer patients using the eighth TNM/AJCC classification system: a comparative study. Thyroid. 2018;28(2):201–9. https://doi.org/10.1089/thy.2017.0265.
Tuttle RM, Tala H, Shah J, Leboeuf R, Ghossein R, Gonen M, 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. https://doi.org/10.1089/thy.2010.0178.
Verburg FA, Mäder U, Tanase K, Thies ED, Diessl S, Buck AK, et al. Life expectancy is reduced in differentiated thyroid cancer patients ≥45 years old with extensive local tumor invasion, lateral lymph node, or distant metastases at diagnosis and normal in all other DTC patients. J Clin Endocrinol Metab. 2013;98(1):172–80.
Park HS, Roman SA, Sosa JA. Treatment patterns of aging Americans with differentiated thyroid cancer. Cancer. 2010;116(1):20–30. https://doi.org/10.1002/cncr.24717.
Haymart MR, Banerjee M, Stewart AK, Koenig RJ, Birkmeyer JD, Griggs JJ. Use of radioactive iodine for thyroid cancer. JAMA. 2011;306:721–8.
Sosa JA, Mehta PJ, Wang TS, Boudourakis L, Roman SA. A population-based study of outcomes from thyroidectomy in aging Americans: at what cost? J Am Coll Surg. 2008;206:1097–105.
Coburn MC, Wanebo HJ. Age correlates with increased frequency of high risk factors in elderly patients with thyroid cancer. Am J Surg. 1995;170:471–5.
Chakravarty D, Santos E, Ryder M, Knauf JA, Liao XH, West BL, et al. Small-molecule MAPK inhibitors restore radioiodine incorporation in mouse thyroid cancers with conditional BRAF activation. J Clin Invest. 2011;121:4700–11.
Fellmer PT, Sato K, Tanaka R, Okamoto T, Kato Y, Kobayashi M, et al. Vascular endothelial growth factor-C gene expression in papillary and follicular thyroid carcinomas. Surgery. 1999;126:1056–61.
Ronga G, Filesi M, Montesano T, di Nicola AD, Pace C, Travascio L, et al. Lung metastases from differentiated thyroid carcinoma. A 40 years’ experience. Q J Nucl Med Mol Imaging. 2004;48:12–9.
Schlumberger M, Brose M, Elisei R, Leboulleux S, Luster M, Pitoia F, et al. Definition and management of radioactive iodine-refractory differentiated thyroid cancer. Lancet Diabetes Endocrinol. 2014;2:356–8. Crossref, Medline
Feine U, Lietzenmayer R, Hanke JP, Held J, Wohrle H, Muller-Schauenburg W. Fluorine-18-FDG and iodine-131-iodide uptake in thyroid cancer. J Nucl Med. 1996;37:1468–72.
Rubino C, de Vathaire F, Dottorini ME, Hall P, Schvartz C, Couette JE, et al. Second primary malignancies in thyroid cancer patients. Br J Cancer. 2003;89:1638–44.
Ringel MD. Metastatic dormancy and progression in thyroid cancer: targeting cells in the metastatic frontier. Thyroid. 2011;21(5):487–92. https://doi.org/10.1089/thy.2011.2121.
• Brose MS, Worden FP, Newbold KL, Guo M, Hurria A. Effect of age on the efficacy and safety of lenvatinib in radioiodine-refractory differentiated thyroid cancer in the phase III select trial. J Clin Oncol. 2017;35(23):2692–9. https://doi.org/10.1200/JCO.2016.71.6472. This article shows increased incidence of toxicity in the elderly population but no significant increase in PFS. This was a subset analysis of the SELECT trial using lenvatinib in RAIRD
Sherman SI. Cytotoxic chemotherapy for differentiated thyroid carcinoma. Clin Oncol. 2010;22:464–8.
Xing M. Molecular pathogenesis and mechanisms of thyroid cancer. Nat Rev Cancer. 2013;13:184–99.
Elisei R, Ugolini C, Viola D, Lupi C, Biagini A, Giannini R, et al. BRAF (V600E) mutation and outcome of patients with papillary thyroid carcinoma: a 15-year median follow-up study. J Clin Endocrinol Metab. 2008;93(10):3943–9. https://doi.org/10.1210/jc.2008-0607.
• Schlumberger M, Tahara M, Wirth LJ, Robinson B, Brose MS, Elisei R, et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med. 2015;372:621–30. Crossref, Medline. This trial showed the efficacy of lenvatinib in RAIRD. Median age was 63 in this study with improved progression-free survival at the cost of increased toxicity.
Eskens FA, Verweij J. The clinical toxicity profile of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR) targeting angiogenesis inhibitors; a review. Eur J Cancer. 2006;42:3127–39.
• Brose MS, et al. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet. 2014;384:319–28. https://doi.org/10.1016/S0140-6736(14)60421-9. This study shows that there is a significant improvement in PFS with the use of sorafenib as compared to placebo in RAIRD.
• Results of randomized phase II trial of dabrafenib versus dabrafenib plus trametinib in BRAF-mutated papillary thyroid carcinoma. https://meetinglibrary.asco.org/record/145877/abstract. This was a phase II trial looking at BRAF mutation in papillary thyroid cancer and usage of BRAF inhibitors.
Brose MS, Cabanillas ME, Cohen EEW, et al. An open-label, multi-center phase 2 study of the BRAF inhibitor vemurafenib in patients with metastatic or unresectable papillary thyroid cancer (PTC) positive for the BRAF V600 mutation and resistant to radioactive iodine (NCT01286753, No25530). Eur J Cancer. 2013;49(Suppl. 3):abstr LBA28.
White PS, Pudusseri A, Lee SL, and Omar E. Intermittent Dosing of Dabrafenib and Trametinib in Metastatic BRAF V600E Mutated Papillary Thyroid Cancer: Two Case Reports. Published Online:1 Sep 2017. https://doi.org/10.1089/thy.2017.0106.
National Comprehensive Cancer Network. Clinical practice guidelines in oncology. Thyroid carcinoma. Version 1.2016. Fort Washington, PA, National Comprehensive Cancer Network. 2016.
A Study to Try to Bring Back Radioiodine Sensitivity in Patients With Advanced Thyroid Cancer. Obtained from: https://clinicaltrials.gov/ct2/show/NCT03469011.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
Rohit Gosain, Jonathan S. Alexander, Amitoj Gill, and Cesar Perez declare they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Additional information
This article is part of the Topical Collection on Geriatric Oncology
Rights and permissions
About this article
Cite this article
Gosain, R., Alexander, J.S., Gill, A. et al. Radioactive Iodine-Refractory Differentiated Thyroid Cancer in the Elderly. Curr Oncol Rep 20, 82 (2018). https://doi.org/10.1007/s11912-018-0736-4
Published:
DOI: https://doi.org/10.1007/s11912-018-0736-4