Skip to main content

Advertisement

SpringerLink
Log in

Radioactive Iodine-Refractory Differentiated Thyroid Cancer in the Elderly

  • Geriatric Oncology (AR MacKenzie, Section Editor)
  • Published:
Current Oncology Reports Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 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.

    Article  PubMed  Google Scholar 

  2. 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.

    Article  PubMed  Google Scholar 

  3. 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.

  4. 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.

    Google Scholar 

  5. 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.

    Article  CAS  PubMed  Google Scholar 

  6. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. 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.

    Article  CAS  PubMed  Google Scholar 

  8. 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.

    Article  PubMed  Google Scholar 

  9. Haymart MR, Banerjee M, Stewart AK, Koenig RJ, Birkmeyer JD, Griggs JJ. Use of radioactive iodine for thyroid cancer. JAMA. 2011;306:721–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. 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.

    Article  PubMed  Google Scholar 

  11. 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.

    Article  CAS  PubMed  Google Scholar 

  12. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. 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.

    Article  CAS  PubMed  Google Scholar 

  14. 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.

    CAS  PubMed  Google Scholar 

  15. 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

    Article  PubMed  Google Scholar 

  16. 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.

    CAS  PubMed  Google Scholar 

  17. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  19. • 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

    Article  PubMed  CAS  Google Scholar 

  20. Sherman SI. Cytotoxic chemotherapy for differentiated thyroid carcinoma. Clin Oncol. 2010;22:464–8.

    Article  CAS  Google Scholar 

  21. Xing M. Molecular pathogenesis and mechanisms of thyroid cancer. Nat Rev Cancer. 2013;13:184–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. 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.

    Article  CAS  PubMed  Google Scholar 

  23. • 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.

    Article  CAS  Google Scholar 

  24. 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.

    Article  CAS  PubMed  Google Scholar 

  25. • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. • 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.

  27. 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.

    Google Scholar 

  28. 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.

    Article  PubMed  Google Scholar 

  29. National Comprehensive Cancer Network. Clinical practice guidelines in oncology. Thyroid carcinoma. Version 1.2016. Fort Washington, PA, National Comprehensive Cancer Network. 2016.

  30. A Study to Try to Bring Back Radioiodine Sensitivity in Patients With Advanced Thyroid Cancer. Obtained from: https://clinicaltrials.gov/ct2/show/NCT03469011.

Download references

Author information

Authors and Affiliations

  1. Division of Hematology and Medical Oncology, Roswell Park Comprehensive Cancer Center, University of Buffalo School of Medicine, Buffalo, NY, 14263, USA

    Rohit Gosain

  2. Division of Hematology and Medical Oncology, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA

    Jonathan S. Alexander & Amitoj Gill

  3. Sylvester Comprehensive Cancer Center, University of Miami - Miller School of Medicine, Miami, FL, USA

    Cesar Perez

Authors
  1. Rohit Gosain
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jonathan S. Alexander
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Amitoj Gill
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cesar Perez
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rohit Gosain.

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

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

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

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11912-018-0736-4

Keywords

Search

Navigation