Real-life management and outcome of thyroid carcinoma-related bone metastases: results from a nationwide multicenter experience
Purpose and Patients
The M.O.S.CA.TI. (Metastases of the Skeleton from CArcinoma of the ThyroId) is a multicenter, retrospective study investigating the real-life outcome and management of bone metastases (BM) in 143 patients (63 M, 80 F; median age 64 years, range 11–87) with differentiated thyroid carcinoma (DTC).
Radio-active iodine (RAI) treatment was performed in 131 patients (91.6%), surgical approach and/or external radiotherapy in 68 patients (47.6%), and anti-resorptive bone-active drugs in 32 patients (22.4%; in 31 zoledronate and in one denosumab). At the start of treatment, 24 patients (75.0%) receiving anti-resorptive bone-active drugs had at least one clinical skeletal-related event (SRE) (p < 0.001). One or more clinical SREs (pathological fractures and/or malignant hypercalcemia and/or spinal cord compression) developed in 53 patients (37.1%). Development of SREs was significantly associated with metachronous BM (hazard ratio (HR) 2.04; p = 0.04), localization of BM to cervical spine (HR 3.89; p = 0.01), and lack of avid RAI uptake (HR 2.66; p = 0.02). Thirty-nine patients (27.3%) died in correlation with development of SREs (HR 6.97; p = 0.006) and localization of BM to the hip (HR 3.86; p = 0.02). Moreover, overall mortality was significantly decreased by RAI therapy (HR 0.10; p = 0.02), whereas no significant effects were induced by bone-active drugs (p = 0.36), external radiotherapy (p = 0.54), and surgery (p = 0.43) of BM.
SREs are very frequent in BM from DTC and they impact patient survival. In the real life, the use of bone-active drugs is currently limited to zoledronate in patients with pre-existing SREs. In this clinical setting, RAI therapy, but not zoledronate, decreased mortality.
KeywordsThyroid carcinoma Bone metastases Zoledronate Denosumab-radioiodine
This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector. The study was partially supported by G.I.O.S.E.G. (Glucocorticoid-induced osteoporosis and Skeletal Endocrinology Group).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
- 2.C. Durante, N. Haddy, E. Baudin, S. Leboulleux, D. Hartl, J.P. Travagli, B. Caillou, M. Ricard, J.D. Lumbroso, F. DeVathaire, 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, 2892–2899 (2006)CrossRefPubMedGoogle Scholar
- 7.M. Tucci, A. Mosca, G. Lamanna, F. Porpiglia, M. Terzolo, F. Vana, C. Cracco, L. Russo, G. Gorzegno, M. Tampellini, M. Torta, G. Reimondo, M. Poggio, R.M. Scarpa, A. Angeli, L. Dogliotti, A. Berruti, Prognostic significance of disordered calcium metabolism in hormone-refractory prostate cancer patients with metastatic bone disease. Prostate Cancer Prostatic Dis. 12, 94–99 (2009)CrossRefPubMedGoogle Scholar
- 8.D.S. Cooper, G.M. Doherty, B.R. Haugen, R.T. Kloos, S.L. Lee, S.J. Mandel, E.L. Mazzaferri, B. McIver, F. Pacini, M. Schlumberger, S.I. Sherman, D.L. Steward, R.M. Tuttle, Revised American Thyroid Association Management Guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 19, 1167–1214 (2009)CrossRefPubMedGoogle Scholar
- 9.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, 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, 1–133 (2016)CrossRefPubMedPubMedCentralGoogle Scholar
- 11.G. Vitale, F. Fonderico, A. Martignetti, M. Caraglia, A. Ciccarelli, V. Nuzzo, A. Abbruzzese, G. Lupoli, Pamidronate improves the quality of life and induces clinical remission of bone metastases in patients with thyroid cancer. Br. J. Cancer 84, 1586–1590 (2001)CrossRefPubMedPubMedCentralGoogle Scholar
- 12.A. Lipton, K. Fizazi, A.T. Stopeck, D.H. Henry, M.R. Smith, N. Shore, M. Martin, S. Vadhan-Raj, J.E. Brown, G.E. Richardson, F. Saad, D.A. Yardley, K. Zhou, A. Balakumaran, A. Braun, Effect of denosumab versus zoledronic acid in preventing skeletal-related events in patients with bone metastases by baseline characteristics. Eur. J. Cancer 53, 75–83 (2016)CrossRefPubMedGoogle Scholar
- 13.J. Liu, W. Huang, R. Zhou, S. Jia, W. Tang, Y. Luo, J. Zhang Bisphosphonates in the treatment of patients with metastatic breast, lung, and prostate cancer: a meta-analysis. Medicine 94, e2014 (2015)Google Scholar
- 14.D. Santini, G. Procopio, C. Porta, T. Ibrahim, S. Barni, C. Mazzara, A. Fontana, A. Berruti, R. Berardi, B. Vincenzi, C. Ortega, D. Ottaviani, G. Carteni, G. Lanzetta, V. Virzì, M. Santoni, N. Silvestris, M.A. Satolli, E. Collovà, A. Russo, G. Badalamenti, S.L. Fedeli, F.M. Tanca, V. Adamo, E. Maiello, R. Sabbatini, A. Felici, S. Cinieri, G. Tonini, S. Bracarda, Natural history of malignant bone disease in renal cancer: final results of an Italian bone metastasis survey. PLoS ONE 30, e83026 (2013)CrossRefGoogle Scholar
- 16.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, 598–605 (1996)PubMedGoogle Scholar
- 20.Y.E. Nikiforov, R.R. Seethala, G. Tallini, Z.W. Baloch, F. Basolo, L.D. Thompson, J.A. Barletta, B.M. Wenig, A. Al Ghuzlan, K. Kakudo, T.J. Giordano, V.A. Alves, E. Khanafshar, S.L. Asa, A.K. El-Naggar, W.E. Gooding, S.P. Hodak, R.V. Lloyd, G. Maytal, O. Mete, M.N. Nikiforova, V. Nosé, M. Papotti, D.N. Poller, P.M. Sadow, A.S. Tischler, R.M. Tuttle, K.B. Wall, V.A. LiVolsi, G.W. Randolph, R.A. Ghossein, Nomenclature revision for encapsulated follicular variant of papillary thyroid carcinoma: a paradigm shift to reduce overtreatment of indolent tumors. JAMA Oncol. 2, 1023–1029 (2016)CrossRefPubMedPubMedCentralGoogle Scholar
- 21.E. Hindié, P. Zanotti-Fregonara, I. Keller, F. Duron, J.Y. Devaux, M. Calzada-Nocaudie, E. Sarfati, J.L. Moretti, P. Bouchard, M.E. Toubert, Bone metastases of differentiated thyroid cancer: impact of early 131I-based detection on outcome. Endocr. Rel. Cancer 14, 799–807 (2007)CrossRefGoogle Scholar
- 22.F.A. Verburg, C. Aktolun, A. Chiti, S. Frangos, L. Giovanella, M. Hoffmann, I. Iakovou, J. Mihailovic, B.J. Krause, W. Langsteger, M. Luster, Why the European Association of Nuclear Medicine has declined to endorse the 2015 American Thyroid Association Management Guidelines for adult patients with thyroid nodules and differentiated thyroid cancer. Eur. J. Nucl. Med. Mol. Imaging 43, 1001–1005 (2016)CrossRefPubMedGoogle Scholar
- 32.R. Pedersini, S. Monteverdi, G. Mazziotti, V. Amoroso, E. Roca, F. Maffezzoni, L. Vassalli, F. Rodella, A.M. Formenti, S. Frara, R. Maroldi, A. Berruti, E. Simoncini, A. Giustina, Morphometric vertebral fractures in breast cancer patients treated with adjuvant aromatase inhibitor therapy: a cross-sectional study. Bone 97, 147–152 (2017)CrossRefPubMedGoogle Scholar
- 33.G. Mazziotti, F. Sorvillo, M. Piscopo, M. Cioffi, P. Pilla, B. Biondi, S. Iorio, A. Giustina, G. Amato, C. Carella, Recombinant human TSH modulates in vivo C-telopeptides of type-1 collagen and bone alkaline phosphatase, but not osteoprotegerin production in postmenopausal women monitored for differentiated thyroid carcinoma. J. Bone Miner. Res. 20, 480–486 (2005)CrossRefPubMedGoogle Scholar
- 35.G. Mazziotti, M. Mormando, A. Cristiano, A. Bianchi, T. Porcelli, A. Giampietro, F. Maffezzoni, V. Serra, L. De Marinis, A. Giustina, Association between l-thyroxine treatment, GH deficiency, and radiological vertebral fractures in patients with adult-onset hypopituitarism. Eur. J. Endocrinol. 170, 893–899 (2014)CrossRefPubMedGoogle Scholar
- 36.M.O. Bernier, L. Leenhardt, C. Hoang, A. Aurengo, J.Y. Mary, F. Menegaux, E. Enkaoua, G. Turpin, J. Chiras, G. Saillant, G. Hejblum, Survival and therapeutic modalities in patients with bone metastases of differentiated thyroid carcinomas. J. Clin. Endocrinol. Metab. 86, 1568–1573 (2001)CrossRefPubMedGoogle Scholar
- 39.R.J. Weiss, W. Ekström, B.H. Hansen, J. Keller, M. Laitinen, C. Trovik, O. Zaikova, R. Wedin, Pathological subtrochanteric fractures in 194 patients: a comparison of outcome after surgical treatment of pathological and non-pathological fractures. J. Surg. Oncol. 107, 498–504 (2013)CrossRefPubMedGoogle Scholar
- 42.Y.M. Choi, W.G. Kim, H. Kwon, M.J. Jeon, J.J. Lee, J.S. Ryu, E.G. Hong, T.Y. Kim, Y.K. Shong, W.B. Kim, Early prognostic factors at the time of diagnosis of bone metastasis in patients with bone metastases of differentiated thyroid carcinoma. Eur. J. Endocrinol. 175, 165–172 (2016)CrossRefPubMedGoogle Scholar
- 45.K. Fizazi, A. Lipton, X. Mariette, J.J. Body, Y. Rahim, J.R. Gralow, G. Gao, L. Wu, W. Sohn, S. Jun, Randomized phase II trial of denosumab in patients with bone metastases from prostate cancer, breast cancer, or other neoplasms after intravenous bisphosphonates. J. Clin. Oncol. 27, 1564–1571 (2009)CrossRefPubMedGoogle Scholar