, Volume 66, Issue 2, pp 254–265 | Cite as

Clinical outcomes and prognostic factors in patients with no less than three distant organ system metastases from differentiated thyroid carcinoma

  • Xin-Yun Zhang
  • Jian-Wen Sun
  • Zhong-Ling Qiu
  • Yang Wang
  • Xiao-Yue Chen
  • Jin-Hua ZhaoEmail author
  • Quan-Yong LuoEmail author
Original Article



For patients with differentiated thyroid carcinoma (DTC), distant metastases are commonly identified in the lungs and bones. However, they are relatively rare in other distant organs, such as the liver, kidneys, or brain. The aim of the current study was to describe the clinical outcomes and evaluate the prognostic factors of patients with no less than three different distant organ system metastases from DTC.


This study retrospectively identified 717 patients diagnosed with DTC with distant metastases between January 2005 and December 2017. Patient response to radioactive iodine (RAI) therapy was monitored by changes in serum thyroglobulin levels and imaging changes. Five-year and 10-year overall survival (OS) rates were calculated by the Kaplan–Meier methods and Cox proportional hazards.


Among the 717 participants, 37 (5.16%) patients had no less than three different distant organ system metastases from DTC. Five-year and 10-year OS were 45.9% and 37.8% in patients with three or more distant organ system metastases while 74.5% and 64.9% in individuals with one or two distant organ system metastases, respectively. RAI avidity and RAIR-DTC were main independent prognostic factors influencing the clinical outcomes for both groups of patients. The presence of 3 or more different distant organ system metastases was the only independent prognostic factors for 10-year OS by multivariate analysis.


Patients with no less than three distant organ system metastases from DTC had poor prognosis. RAI avidity and RAIR-DTC were main factors influencing overall survival for patients with distant metastases from DTC in both groups.


Differentiated thyroid carcinoma Distant metastases Multiple distant organ system metastases Radioactive iodine therapy Overall survival 



The authors thank the American Journal Experts for their help with the edition for proper English language, grammar, punctuation, spelling, and overall style by one or more of the highly qualified native English-speaking editors for this paper. This study was supported by the National Natural Science Foundation of China (Grant number 81671712) and the Shanghai Key Discipline of Medical Imaging (Grant number 2017ZZ02005).

Author contributions

X.Y.Z. and Z.L.Q. designed the study. X.Y.C. and J.W.S. conducted the statistical analysis. Y.W. collected the clinical data. X.Y.Z. wrote the whole paper. J.H.Z. and Q.Y.L. supervised and edited the paper. All authors read and approved the final paper.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    R.L. Siegel, K.D. Miller, A. Jemal, Cancer statistics, 2018. CA Cancer J. Clin. 68(1), 7–30 (2018). CrossRefPubMedGoogle Scholar
  2. 2.
    F. Bray, J. Ferlay, I. Soerjomataram, R.L. Siegel, L.A. Torre, A. Jemal. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. (2018). Google Scholar
  3. 3.
    C.M. Kitahara, J.A. Sosa, The changing incidence of thyroid cancer. Nat. Rev. Endocrinol. 12(11), 646–653 (2016). CrossRefPubMedGoogle Scholar
  4. 4.
    L. Furuya-Kanamori, A. Sedrakyan, A.A. Onitilo, N. Bagheri, P. Glasziou, S.A.R. Doi, Differentiated thyroid cancer: millions spent with no tangible gain? Endocr. Relat. Cancer 25(1), 51–57 (2018). CrossRefPubMedGoogle Scholar
  5. 5.
    S.Y. Sohn, H.I. Kim, Y.N. Kim, T.H. Kim, S.W. Kim, J.H. Chung, Prognostic indicators of outcomes in patients with lung metastases from differentiated thyroid carcinoma during long-term follow-up. Clin. Endocrinol. 88(2), 318–326 (2018). CrossRefGoogle Scholar
  6. 6.
    P. Choksi, M. Papaleontiou, C. Guo, F. Worden, M. Banerjee, M. Haymart, Skeletal complications and mortality in thyroid cancer: a population-based study. J. Clin. Endocrinol. Metab. 102(4), 1254–1260 (2017). CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    A.B. Sheikh, A. Akhtar, U. Tariq, A.A.E. Sheikh, F.S. Siddiqui, M.M. Bukhari, Skull metastasis extending to the superior sagittal sinus: an unfamiliar presentation of papillary thyroid carcinoma. Cureus 10(6), e2738 (2018). CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    H.J. Song, Z.L. Qiu, C.T. Shen, W.J. Wei, Q.Y. Luo, Pulmonary metastases in differentiated thyroid cancer: efficacy of radioiodine therapy and prognostic factors. Eur. J. Endocrinol. 173(3), 399–408 (2015). CrossRefPubMedGoogle Scholar
  9. 9.
    Q.Y. Luo, Q. Luo, L.B. Chen, Y.L. Yu, H.K. Lu, R.S. Zhu, Multiple subdermal metastases from papillary thyroid cancer. Thyroid 18(8), 907–908 (2008). CrossRefPubMedGoogle Scholar
  10. 10.
    L.Y. Wang, F.L. Palmer, I.J. Nixon, D. Thomas, S.G. Patel, A.R. Shaha, J.P. Shah, R.M. Tuttle, I. Ganly, Multi-organ distant metastases confer worse disease-specific survival in differentiated thyroid cancer. Thyroid 24(11), 1594–1599 (2014). CrossRefPubMedGoogle Scholar
  11. 11.
    M.E. Cabanillas, D.G. McFadden, C. Durante, Thyroid cancer. Lancet 388(10061), 2783–2795 (2016). CrossRefPubMedGoogle Scholar
  12. 12.
    B.R. Haugen, E.K. Alexander, K.C. Bible, G.M. Doherty, S.J. Mandel, Y.E. Nikiforov, F. Pacini, G.W. Randolph, A.M. Sawka, M. Schlumberger, K.G. Schuff, S.I. Sherman, J.A. Sosa, D.L. Steward, R.M. Tuttle, L. Wartofsky, 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 26(1), 1–133 (2016). CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    H.G. Vuong, U.N.P. Duong, T.Q. Pham, H.M. Tran, N. Oishi, K. Mochizuki, T. Nakazawa, L. Hassell, R. Katoh, T. Kondo, Clinicopathological risk factors for distant metastasis in differentiated thyroid carcinoma: a meta-analysis. World J. Surg. 42(4), 1005–1017 (2018). CrossRefPubMedGoogle Scholar
  14. 14.
    H. Lim, S.S. Devesa, J.A. Sosa, D. Check, C.M. Kitahara, Trends in thyroid cancer incidence and mortality in the United States, 1974-2013. J. Am. Med. Assoc. 317(13), 1338–1348 (2017). CrossRefGoogle Scholar
  15. 15.
    C.A. Benbassat, S. Mechlis-Frish, D. Hirsch, Clinicopathological characteristics and long-term outcome in patients with distant metastases from differentiated thyroid cancer. World J. Surg. 30(6), 1088–1095 (2006). CrossRefPubMedGoogle Scholar
  16. 16.
    D. Casara, D. Rubello, G. Saladini, G. Masarotto, A. Favero, M.E. Girelli, B. Busnardo, Different features of pulmonary metastases in differentiated thyroid cancer: natural history and multivariate statistical analysis of prognostic variables. J. Nucl. Med. 34(10), 1626–1631 (1993)PubMedGoogle Scholar
  17. 17.
    B.H. Lang, K.P. Wong, C.Y. Cheung, K.Y. Wan, C.Y. Lo, Evaluating the prognostic factors associated with cancer-specific survival of differentiated thyroid carcinoma presenting with distant metastasis. Ann. Surg. Oncol. 20(4), 1329–1335 (2013). CrossRefPubMedGoogle Scholar
  18. 18.
    Y. Saito, K. Sugino, H. Takami, K. Matsuzu, T. Uruno, K. Ohkuwa, W. Kitagawa, M. Nagahama, H. Kawakubo, K. Ito, Y. Kitagawa. Clinical status and treatment of liver metastasis of differentiated thyroid cancer using tyrosine kinase inhibitors. World J. Surg. (2018). CrossRefGoogle Scholar
  19. 19.
    A.R. Shaha, J.P. Shah, T.R. Loree, Differentiated thyroid cancer presenting initially with distant metastasis. Am. J. Surg. 174(5), 474–476 (1997)CrossRefGoogle Scholar
  20. 20.
    M. Davidson, R.J. Olsen, A.A. Ewton, R.J. Robbins, Pancreas metastases from papillary thyroid carcinoma: a review of the literature. Endocr. Pract. 23(12), 1425–1429 (2017). CrossRefPubMedGoogle Scholar
  21. 21.
    Y.W. Hong, J.D. Lin, M.C. Yu, C.C. Hsu, Y.S. Lin, Outcomes and prognostic factors in thyroid cancer patients with cranial metastases: a retrospective cohort study of 4,683 patients. Int J. Surg. 55, 182–187 (2018). CrossRefPubMedGoogle Scholar
  22. 22.
    K. Korhonen, H. Zhuang, Pediatric patient with cerebral metastasis from papillary thyroid cancer. Clin. Nucl. Med. 43(6), 471–473 (2018). CrossRefPubMedGoogle Scholar
  23. 23.
    D. Albano, M.B. Panarotto, R. Durmo, C. Rodella, F. Bertagna, R. Giubbini, Clinical and prognostic role of detection timing of distant metastases in patients with differentiated thyroid cancer. Endocrine 63(1), 79–86 (2019). CrossRefPubMedGoogle Scholar
  24. 24.
    M.C. Kreissl, M.J.R. Janssen, J. Nagarajah, Current treatment strategies in metastasized differentiated thyroid cancer. J. Nucl. Med. 60(1), 9–15 (2019). CrossRefPubMedGoogle Scholar
  25. 25.
    H. Kim, H.I. Kim, S.W. Kim, J. Jung, M.J. Jeon, W.G. Kim, T.Y. Kim, H.K. Kim, H.C. Kang, J.M. Han, Y.Y. Cho, T.H. Kim, J.H. Chung, Prognosis of differentiated thyroid carcinoma with initial distant metastasis: a multicenter study in Korea. Endocrinol. Metab. 33(2), 287–295 (2018). CrossRefGoogle Scholar
  26. 26.
    J.D. Lin, S.F. Kuo, B.Y. Huang, S.F. Lin, S.T. Chen, The efficacy of radioactive iodine for the treatment of well-differentiated thyroid cancer with distant metastasis. Nucl. Med Commun. 39(12), 1091–1096 (2018). CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    N.D. Perrier, J.D. Brierley, R.M. Tuttle, Differentiated and anaplastic thyroid carcinoma: major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J. Clin. 68(1), 55–63 (2018). CrossRefPubMedGoogle Scholar
  28. 28.
    G. Mazziotti, A.M. Formenti, M.B. Panarotto, E. Arvat, A. Chiti, A. Cuocolo, M.E. Dottorini, C. Durante, L. Agate, S. Filetti, F. Felicetti, A. Filice, L. Pace, T. Pellegrino, M. Rodari, M. Salvatori, C. Tranfaglia, A. Versari, D. Viola, S. Frara, A. Berruti, A. Giustina, R. Giubbini, Real-life management and outcome of thyroid carcinoma-related bone metastases: results from a nationwide multicenter experience. Endocrine 59(1), 90–101 (2018). CrossRefPubMedGoogle Scholar
  29. 29.
    D.H. Shah, A.M. Samuel, Metastasis to the liver in well-differentiated carcinoma of the thyroid. Thyroid 6(6), 607–611 (1996). CrossRefPubMedGoogle Scholar
  30. 30.
    C. Durante, N. Haddy, E. Baudin, S. Leboulleux, D. Hartl, J.P. Travagli, B. Caillou, M. Ricard, J.D. Lumbroso, F. De Vathaire, M. Schlumberger, Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy. J. Clin. Endocrinol. Metab. 91(8), 2892–2899 (2006). CrossRefPubMedGoogle Scholar
  31. 31.
    P.M. Manohar, L.J. Beesley, E.L. Bellile, F.P. Worden, A.M. Avram, Prognostic value of FDG-PET/CT metabolic parameters in metastatic radioiodine-refractory differentiated thyroid cancer. Clin. Nucl. Med. 43(9), 641–647 (2018). CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    M. Schlumberger, C. Challeton, F. De Vathaire, J.P. Travagli, P. Gardet, J.D. Lumbroso, C. Francese, F. Fontaine, M. Ricard, C. Parmentier, Radioactive iodine treatment and external radiotherapy for lung and bone metastases from thyroid carcinoma. J. Nucl. Med. 37(4), 598–605 (1996)PubMedGoogle Scholar
  33. 33.
    Z.L. Qiu, H.J. Song, Y.H. Xu, Q.Y. Luo, Efficacy and survival analysis of 131I therapy for bone metastases from differentiated thyroid cancer. J. Clin. Endocrinol. Metab. 96(10), 3078–3086 (2011). CrossRefPubMedGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Nuclear MedicineShanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghaiChina
  2. 2.Department of Nuclear MedicineShanghai General Hospital, Shanghai Jiao Tong University School of MedicineShanghaiChina

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