International Orthopaedics

, Volume 43, Issue 2, pp 483–489 | Cite as

Denosumab does not decrease the risk of lung metastases from bone giant cell tumour

  • Shinji TsukamotoEmail author
  • Andreas F. MavrogenisEmail author
  • Giulio Leone
  • Alberto Righi
  • Manabu Akahane
  • Piergiuseppe Tanzi
  • Akira Kido
  • Kanya Honoki
  • Yasuhito Tanaka
  • Davide Maria Donati
  • Costantino ErraniEmail author
Original Paper



There are conflicting reports on the effect of denosumab on lung metastases in patients with giant cell tumor (GCT) of bone. To address these reports, we performed this study to determine if denosumab prevents lung metastasis and to evaluate univariate and multivariate predictors for lung metastases in these patients.

Materials and methods

We retrospectively studied 381 GCT patients with surgery alone and 30 GCT patients with surgery and denosumab administration. The median follow-up was 85.2 months (IQR, 54.2–124.4 months). We evaluated lung metastases and local recurrences, univariate and multivariate predictors for lung metastases, response, and adverse events of denosumab administration.


The occurrence of lung metastases was similar (surgery alone 4.7%, 18 patients; denosumab administration 3.3%, 1 patient); however, the occurrence of local recurrences was significantly higher in the patients with denosumab administration. Denosumab administration was not an important predictor for lung metastases; Campanacci stage and type of surgery were the only univariate predictors for lung metastases, and type of surgery and local recurrence were the only multivariate predictors for lung metastases. Histology showed viable tumour in all tumor specimens of the patients with denosumab administration.


Denosumab does not decrease the risk of lung metastases in patients with bone GCT; the only important predictors for lung metastases in these patients are type of surgery and local recurrence. However, because the number of patients with lung metastases was small for a multivariate analysis, the possibility of denosumab’s effect could not be completely eliminated.


Giant cell tumour of bone Denosumab Metastasis Lungs 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the independent ethics committee of senior author’s institution and is registered with (identifier NCT02996734).

Informed consent

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


  1. 1.
    Fletcher CDM, Bridge JA, Hogendoorn P, Mertens F (2013) WHO classification of tumours of soft tissue and bone. Lyon, IARC, pp 321–324Google Scholar
  2. 2.
    Dominkus M, Ruggieri P, Bertoni F et al (2006) Histologically verified lung metastases in benign giant cell tumours-14 cases from a single institution. Int Orthop 30:499–504. CrossRefGoogle Scholar
  3. 3.
    Chan CM, Adler Z, Reith JD, Gibbs CP (2015) Risk factors for pulmonary metastases from giant cell tumor of bone. J Bone Joint Surg Am 97:420–428. CrossRefGoogle Scholar
  4. 4.
    Rosario M, Kim H-S, Yun JY, Han I (2017) Surveillance for lung metastasis from giant cell tumor of bone. J Surg Oncol 116:907–913. CrossRefGoogle Scholar
  5. 5.
    Wang B, Chen W, Xie X et al (2017) Development and validation of a prognostic index to predict pulmonary metastasis of giant cell tumor of bone. Oncotarget 8:108054–108063. Google Scholar
  6. 6.
    Katz E, Nyska M, Okon E, Zajicek G, Robin G (1987) Growth rate analysis of lung metastases from histologically benign giant cell tumor of bone. Cancer 59(10):1831–1836CrossRefGoogle Scholar
  7. 7.
    Siebenrock KA, Unni KK, Rock MG (1998) Giant-cell tumour of bone metastasising to the lungs. A long-term follow-up J Bone Joint Surg Br 80:43–47CrossRefGoogle Scholar
  8. 8.
    Tubbs WS, Brown LR, Beabout JW et al (1992) Benign giant-cell tumor of bone with pulmonary metastases: clinical findings and radiologic appearance of metastases in 13 cases. AJR Am J Roentgenol 158:331–334. CrossRefGoogle Scholar
  9. 9.
    Errani C, Ruggieri P, Asenzio MAN et al (2010) Giant cell tumor of the extremity: a review of 349 cases from a single institution. Cancer Treat Rev 36:1–7. CrossRefGoogle Scholar
  10. 10.
    O’Donnell RJ, Springfield DS, Motwani HK et al (1994) Recurrence of giant-cell tumors of the long bones after curettage and packing with cement. J Bone Joint Surg Am 76:1827–1833CrossRefGoogle Scholar
  11. 11.
    Viswanathan S, Jambhekar NA (2010) Metastatic giant cell tumor of bone: are there associated factors and best treatment modalities? Clin Orthop 468:827–833. CrossRefGoogle Scholar
  12. 12.
    Chawla S, Henshaw R, Seeger L et al (2013) Safety and efficacy of denosumab for adults and skeletally mature adolescents with giant cell tumour of bone: interim analysis of an open-label, parallel-group, phase 2 study. Lancet Oncol 14:901–908. CrossRefGoogle Scholar
  13. 13.
    Errani C, Tsukamoto S, Mavrogenis AF (2017) How safe and effective is denosumab for bone giant cell tumour? Int Orthop 41(11):2397–2400. CrossRefGoogle Scholar
  14. 14.
    Thomas D, Carriere P, Jacobs I (2010) Safety of denosumab in giant-cell tumour of bone. Lancet Oncol 11:815. CrossRefGoogle Scholar
  15. 15.
    Ueda T, Morioka H, Nishida Y et al (2015) Objective tumor response to denosumab in patients with giant cell tumor of bone: a multicenter phase II trial. Ann Oncol 26(10):2149–2154. CrossRefGoogle Scholar
  16. 16.
    Mak IWY, Evaniew N, Popovic S et al (2014) A translational study of the neoplastic cells of giant cell tumor of bone following neoadjuvant denosumab. J Bone Joint Surg Am 96:e127. CrossRefGoogle Scholar
  17. 17.
    Lau CPY, Huang L, Wong KC, Kumta SM (2013) Comparison of the anti-tumor effects of denosumab and zoledronic acid on the neoplastic stromal cells of giant cell tumor of bone. Connect Tissue Res 54:439–449. CrossRefGoogle Scholar
  18. 18.
    Girolami I, Mancini I, Simoni A et al (2016) Denosumab treated giant cell tumour of bone: a morphological, immunohistochemical and molecular analysis of a series. J Clin Pathol 69:240–247. CrossRefGoogle Scholar
  19. 19.
    Errani C, Tsukamoto S, Leone G et al (2018) Denosumab may increase the risk of local recurrence in patients with giant-cell tumor of bone treated with curettage. J Bone Joint Surg Am 100:496–504. CrossRefGoogle Scholar
  20. 20.
    Matcuk GR, Patel DB, Schein AJ et al (2015) Giant cell tumor: rapid recurrence after cessation of long-term denosumab therapy. Skelet Radiol 44:1027–1031. CrossRefGoogle Scholar
  21. 21.
    Campanacci M, Baldini N, Boriani S, Sudanese A (1987) Giant-cell tumor of bone. J Bone Joint Surg Am 69:106–114CrossRefGoogle Scholar
  22. 22.
    Palmerini E, Chawla NS, Ferrari S et al (2017) Denosumab in advanced/unresectable giant-cell tumour of bone (GCTB): for how long? Eur J Cancer Oxf Engl 1990 76:118–124. CrossRefGoogle Scholar
  23. 23.
    Choi H, Charnsangavej C, Faria SC et al (2007) Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: proposal of new computed tomography response criteria. J Clin Oncol 25:1753–1759. CrossRefGoogle Scholar
  24. 24.
    U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute (2009) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. U.S. May 28. Available at: Accessed on: April 14, 2018
  25. 25.
    Bacci G, Rocca M, Salone M et al (2008) High grade osteosarcoma of the extremities with lung metastases at presentation: treatment with neoadjuvant chemotherapy and simultaneous resection of primary and metastatic lesions. J Surg Oncol 98(6):415–420. CrossRefGoogle Scholar
  26. 26.
    Ciccarese F, Bazzocchi A, Ciminari R et al (2015) The many faces of pulmonary metastases of osteosarcoma: retrospective study on 283 lesions submitted to surgery. Eur J Radiol 84(12):2679–2685. CrossRefGoogle Scholar
  27. 27.
    Kito M, Matusmoto S, Ae K et al (2017) Pulmonary metastasis from giant cell tumor of bone: clinical outcome prior to the introduction of molecular target therapy. Jpn J Clin Oncol 47:529–534. CrossRefGoogle Scholar
  28. 28.
    Moskovszky L, Szuhai K, Krenács T et al (2009) Genomic instability in giant cell tumor of bone. A study of 52 cases using DNA ploidy, relocalization FISH, and array-CGH analysis. Genes Chromosomes Cancer 48:468–479. CrossRefGoogle Scholar

Copyright information

© SICOT aisbl 2018
corrected publication September/2018

Authors and Affiliations

  1. 1.Department of OrthopaedicsNara Medical UniversityNaraJapan
  2. 2.First Department of OrthopaedicsNational and Kapodistrian University of Athens, School of MedicineAthensGreece
  3. 3.Department of OrthopaedicsSan Gerardo HospitalMonzaItaly
  4. 4.Department of PathologyIstituto Ortopedico RizzoliBolognaItaly
  5. 5.Department of Public Health, Health Management, and PolicyNara Medical UniversityNaraJapan
  6. 6.Department of Orthopaedic OncologyIstituto Ortopedico RizzoliBolognaItaly

Personalised recommendations