Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Clinical Sarcoma Research
Published in: Clinical Sarcoma Research 1/2016

Open Access 01-12-2016 | Review

Current status and unanswered questions on the use of Denosumab in giant cell tumor of bone

Authors: Czar Louie Gaston, Robert J. Grimer, Michael Parry, Silvia Stacchiotti, Angelo Paolo Dei Tos, Hans Gelderblom, Stefano Ferrari, Giacomo G. Baldi, Robin L. Jones, Sant Chawla, Paolo Casali, Axel LeCesne, Jean-Yves Blay, Sander P. D. Dijkstra, David M. Thomas, Piotr Rutkowski

Published in: Clinical Sarcoma Research | Issue 1/2016

Login to get access

Abstract

Denosumab is a monoclonal antibody to RANK ligand approved for use in giant cell tumour (GCT) of bone. Due to its efficacy, Denosumab is recommended as the first option in inoperable or metastatic GCT. Denosumab has also been used pre-operatively to downstage tumours with large soft tissue extension to allow for less morbid surgery. The role of Denosumab for conventional limb GCT of bone is yet to be defined. Further studies are required to determine whether local recurrence rates will be decreased with the adjuvant use of Denosumab along with surgery. The long term use and toxicity of this agent is unknown as is the proportion of patients with primary or secondary resistance. It is advised that complicated cases of GCT requiring Denosumab treatment should be referred and followed up at expert centres. Collaborative studies involving further clinical trials and rigorous data collection are strongly recommended to identify the optimum use of this drug.
Literature
1.
Behjati S, Tarpey PS, Presneau N, Scheipl S, Pillay N, Van Loo P, Wedge DC, Cooke SL, Gundem G, Davies H, Nik-Zainal S, Martin S, McLaren S, Goody V, Robinson B, Butler A, Teague JW, Halai D, Khatri B, Myklebost O, Baumhoer D, Jundt G, Hamoudi R, Tirabosco R, Amary MF, Futreal PA, Stratton MR, Campbell PJ, Flanagan AM. Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone. Nat Genet. 2013;45(12):1479–82.CrossRefPubMed
2.
van der Heijden L, van der Geest IC, Schreuder HW, van de Sande MA, Dijkstra PD. Liquid nitrogen or phenolization for giant cell tumor of bone?: a comparative cohort study of various standard treatments at two tertiary referral centers. J Bone Joint Surg Am. 2014;96(5):e35.CrossRefPubMed
3.
Jones KB, DeYoung BR, Morcuende JA, Buckwalter JA. Ethanol as a local adjuvant for giant cell tumor of bone. Iowa Orthop J. 2006;26:69–76.PubMedPubMedCentral
4.
Gaston CL, Bhumbra R, Watanuki M, et al. Does the addition of cement improve the rate of local recurrence after curettage of giant cell tumours in bone? J Bone Joint Surg Br. 2011;93(12):1665–9.CrossRefPubMed
5.
Tse LF, Wong KC, Kumta SM, Huang L, Chow TC, Griffith JF. Bisphosphonates reduce local recurrence in extremity giant cell tumor of bone: a case-control study. Bone. 2008;42(1):68–73.CrossRefPubMed
6.
Gouin F, Rochwerger AR, Di Marco A, Rosset P, Bonnevialle P, Fiorenza F, Anract P. Adjuvant treatment with zoledronic acid after extensive curettage for giant cell tumours of bone. Eur J Cancer. 2014;50(14):2425–31.CrossRefPubMed
7.
Balke M, Schremper L, Gebert C, et al. Giant cell tumor of bone: treatment and outcome of 214 cases. J Cancer Res Clin Oncol. 2008;134(9):969–78.CrossRefPubMed
8.
Kivioja AH, Blomqvist C, Hietaniemi K, et al. Cement is recommended in intralesional surgery of giant cell tumors: a scandinavian sarcoma group study of 294 patients followed for a median time of 5 years. Acta Orthop. 2008;79:86–93.CrossRefPubMed
9.
Klenke FM, Wenger DE, Inwards CY, et al. Giant cell tumor of bone: risk factors for recurrence. Clin Orthop Relat Res. 2011;489(2):591–9 (Epub 2010 Aug 13).CrossRef
10.
Prosser GH, Baloch KG, Tillman RM, et al. Does curettage without adjuvant therapy provide low recurrence rates in giant-cell tumors of bone? Clin Orthop Relat Res. 2005;435:211–8.CrossRefPubMed
11.
Leggon RE, Zlotecki R, Reith J, Scarborough MT. Giant cell tumor of the pelvis and sacrum: 17 cases and analysis of the literature. Clin Orthop Relat Res. 2004;423:196–207.CrossRefPubMed
12.
Martin C, McCarthy EF. Giant cell tumor of the sacrum and spine: series of 23 cases and a review of the literature. Iowa Orthop J. 2010;30:69–75.PubMedPubMedCentral
13.
Bhatia S, Miszczyk L, Roelandts M, et al. Radiotherapy for marginally resected, unresectable or recurrent giant cell tumor of the bone: a rare cancer network study. Rare Tumors. 2011;3(4):e48.CrossRefPubMedPubMedCentral
14.
15.
Zhou M, Yang H, Chen K, et al. Surgical treatment of giant cell tumors of the sacrum and spine combined with pre-operative transarterial embolization. Oncol Lett. 2013;6(1):185–90.PubMedPubMedCentral
16.
Chakravarti A, Spiro IJ, Hug EB, Mankin HJ, Efird JT, Suit HD. Megavoltage radiation therapy for axial and inoperable giant-cell tumor of bone. J Bone Joint Surg Am. 1999;81(11):1566–73.PubMed
17.
Ruka W, Rutkowski P, Morysiński T, et al. The megavoltage radiation therapy in treatment of patients with advanced or difficult giant cell tumors of bone. Int J Radiat Oncol Biol Phys. 2010;78(2):494–8.CrossRefPubMed
18.
Cornelis F, Truchetet ME, Amoretti N, et al. Bisphosphonate therapy for unresectable symptomatic benign bone tumors: a long-term prospective study of tolerance and efficacy. Bone. 2014;58:11–6.CrossRefPubMed
19.
Xu W, Li X, Huang W, et al. Factors affecting prognosis of patients with giant cell tumors of the mobile spine: retrospective analysis of 102 patients in a single center. Ann Surg Oncol. 2013;20(3):804–10.CrossRefPubMed
20.
Agarwal A, Larsen BT, Buadu LD, et al. Denosumab chemotherapy for recurrent giant-cell tumor of bone: a case report of neoadjuvant use enabling complete surgical resection. Case Rep Oncol Med. 2013;2013:496351 (Epub 2013 Jul 30).PubMedPubMedCentral
21.
Mattei TA, Ramos E, Rehman AA, Shaw A, Patel SR, Mendel E. Sustained long-term complete regression of a giant cell tumor of the spine after treatment with Denosumab. Spine J. 2014;14(7):e15–21.CrossRefPubMed
22.
Stewart DJ, Belanger R, Benjamin RS. Prolonged disease-free survival following surgical debulking and high-dose cisplatin/doxorubicin in a patient with bulky metastases from giant cell tumor of bone refractory to “standard” chemotherapy. Am J Clin Oncol. 1995;18(2):144–8.CrossRefPubMed
23.
Yamamoto M, Fukushima T, Sakamoto S, et al. Giant cell tumor of the sphenoid bone: long-term follow-up of two cases after chemotherapy. Surg Neurol. 1998;49(5):547–52.CrossRefPubMed
24.
Mella O, Dahl O, Bang G, et al. Chemotherapy of a malignant, metastasizing giant-cell tumor of bone: report of an unusual case and the response to combination chemotherapy. Cancer. 1982;50(2):207–11.CrossRefPubMed
25.
Thomas D, Henshaw R, Skubitz K, et al. Denosumab in patients with giant cell tumour of bone.: an open-label phase 2 study. Lancet Oncol. 2010;11:275–80.CrossRefPubMed
26.
Chawla S, Henshaw R, Seeger L, et al. 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. 2013;14:901–8.CrossRefPubMed
27.
Huang L, Xu J, Wood DJ, Zheng MH. Gene expression of osteoprotegerin ligand, osteoprotegerin, and receptor activator of NF-kappaB in giant cell tumor of bone: possible involvement in tumor cell-induced osteoclast-like cell formation. Am J Pathol. 2000;156(3):761–7.CrossRefPubMedPubMedCentral
28.
Atkins GJ, Kostakis P, Vincent C, et al. RANK expression as a cell surface marker of human osteoclast precursors in peripheral blood, bone marrow, and giant cell tumors of bone. J Bone Miner Res. 2006;21:1339–49.CrossRefPubMed
29.
30.
Branstetter DG, Nelson SD, Manivel JC, et al. Denosumab induces tumor reduction and bone formation in patients with giant-cell tumor of bone. Clin Cancer Res. 2012;18:4415–24.CrossRefPubMed
31.
Goldenberg MM. Pharmaceutical approval update. Pharm Ther. 2013;38(8):443–5.
32.
Stiacchiotti S, dei Tos P, Gelderblom H, Ferrari S, Parry M, Baldi GG, Jones R, Chawla S, Casali P, LeCesne A, Blay J, Dijkstra S, Thomas D, Rutkowski P. Current status and open questions on Denosumab therapy in giant cell tumor of bone. In: Symposium conducted at the 2015 annual meeting of the connective tissue oncology society, Salt Lake City, USA. 2015.
33.
Karras NA, Polgreen LE, Ogilvie C, Manivel JC, Skubitz KM, Lipsitz E. Denosumab treatment of metastatic giant-cell tumor of bone in a 10-year-old girl. J Clin Oncol. 2013;31(12):200–2.CrossRef
34.
Demirsoy U, Karadogan M, Selek Ö, Anik Y, Aksu G, Müezzinoglu B, Corapcioglu F. Golden bullet-Denosumab: early rapid response of metastatic giant cell tumor of the bone. J Pediatr Hematol Oncol. 2014;36(2):156–8.CrossRefPubMed
35.
Gossai N, Hilgers MV, Polgreen LE, Greengard EG. Critical hypercalcemia following discontinuation of Denosumab therapy for metastatic giant cell tumor of bone. Pediatr Blood Cancer. 2015;62(6):1078–80.CrossRefPubMed
36.
Ulas A, Bulent Akinci M, Silay K, Sendur MA, Sener Dede D, Yalcin B. Denosumab: excellent response of metastatic giant cell tumor of the bone. J BUON. 2015;20(2):666–7.PubMed
37.
Mak IW, Evaniew N, Popovic S, Tozer R, Ghert M. A translational study of the neoplastic cells of giant cell tumor of bone following neoadjuvant Denosumab. J Bone Joint Surg Am. 2014;96(15):e127.CrossRefPubMed
38.
Lau CP, Huang L, Wong KC, Kumta SM. 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. 2013;54(6):439–49.CrossRef
39.
Girolami I, Mancini I, Simoni A, Baldi GG, Simi L, Campanacci D, Beltrami G, Scoccianti G, D’Arienzo A, Capanna R, Franchi A. Denosumab treated giant cell tumour of bone: a morphological, immunohistochemical and molecular analysis of a series. J Clin Pathol. 2015 (Epub ahead of print).
40.
Bussiere JL, Pyrah I, Boyce R, et al. Reproductive toxicity of Denosumab in cynomolgus monkeys. Reprod Toxicol. 2013;42:27–40.CrossRefPubMed
41.
42.
Setsu N, Kobayashi E, Asano N, Yasui N, Kawamoto H, Kawai A, Horiuchi K. Severe hypercalcemia following Denosumab treatment in a juvenile patient. J Bone Miner Metab. 2015 (Epub ahead of print).
43.
Kajizono M, Sada H, Sugiura Y, Soga Y, Kitamura Y, Matsuoka J, Sendo T. Incidence and risk factors of osteonecrosis of the jaw in advanced cancer patients after treatment with zoledronic acid or Denosumab: a retrospective cohort study. Biol Pharm Bull. 2015;38(12):1850–5.CrossRef
44.
Bukata SV, Sudan M, Mendanha W, et al. Considerations for long-term maintenance treatment with Denosumab for stable inoperable giant cell tumor: making a case for spacing of doses after initial response. In: paper presented at the meeting of the connective tissue oncology society, Salt Lake City, USA. 2015.
45.
Watanabe N, Matsumoto S, Shimoji T, Ae K, Tanizawa T, Gokita T, Motoi N, Ueno T, Koizumi M. Early evaluation of the therapeutic effect of Denosumab on tartrate-resistant acid phosphatase 5b expression in a giant cell tumor of bone: a case report. BMC Res Notes. 2014;7:608.CrossRefPubMedPubMedCentral
46.
Lipton A, Steger GG, Figueroa J, Alvarado C, Solal-Celigny P, Body JJ, de Boer R, Berardi R, Gascon P, Tonkin KS, Coleman R, Paterson AH, Peterson MC, Fan M, Kinsey A, Jun S. Randomized active-controlled phase II study of Denosumab efficacy and safety in patients with breast cancer-related bone metastases. J Clin Oncol. 2007;25(28):4431–7.CrossRefPubMed
47.
Thangaraj R, Grimer RJ, Carter SR, Stirling AJ, Spilsbury J, Spooner D. Giant cell tumour of the sacrum: a suggested algorithm for treatment. Eur Spine J. 2010;19:1189–94.CrossRefPubMedPubMedCentral
48.
Akaike K, Suehara Y, Takagi T, Kaneko K, Saito T. An eggshell-like mineralized recurrent lesion in the popliteal region after treatment of giant cell tumor of the bone with Denosumab. Skelet Radiol. 2014;43(12):1767–72.CrossRef
49.
Heijden LV, Sande MA, Hogendoorn PC, Gelderblom H, Dijkstra PD. Neoadjuvant Denosumab for extensive giant cell tumor in os ischium: a case report. Acta Orthop. 2015;86(3):393–5.CrossRefPubMedPubMedCentral
50.
Rutkowski P, Ferrari S, Grimer RJ, Stalley PD, Dijkstra SP, Pienkowski A, Vaz G, Wunder JS, Seeger LL, Feng A, Roberts ZJ, Bach BA. Surgical downstaging in an open-label phase ii trial of Denosumab in patients with giant cell tumor of bone. Ann Surg Oncol. 2015;22(9):2860–8.CrossRefPubMedPubMedCentral
51.
Hakozaki M, Tajino T, Yamada H, Hasegawa O, Tasaki K, Watanabe K, Konno S. Radiological and pathological characteristics of giant cell tumor of bone treated with Denosumab. Diagn Pathol. 2014;9:111.CrossRefPubMedPubMedCentral
52.
53.
Bickels J, Meller I, Shmookler BM, Malawer MM. The role and biology of cryosurgery in the treatment of bone tumors. A review. Acta Orthop Scand. 1999;70(3):308–15.CrossRefPubMed
54.
Ueda T, Morioka H, Nishida Y, Kakunaga S, Tsuchiya H, Matsumoto Y, Asami Y, Inoue T, Yoneda T. Objective tumor response to Denosumab in patients with giant cell tumor of bone: a multicenter phase II trial. Ann Oncol. 2015;26(10):2149–54.CrossRefPubMedPubMedCentral
55.
Aponte-Tinao LA, Piuzzi NS, Roitman P, Farfalli GL. A high-grade sarcoma arising in a patient with recurrent benign giant cell tumor of the proximal tibia while receiving treatment with Denosumab. Clin Orthop Relat Res. 2015;473(9):3050–5.CrossRefPubMed
Metadata
Title
Current status and unanswered questions on the use of Denosumab in giant cell tumor of bone
Authors
Czar Louie Gaston
Robert J. Grimer
Michael Parry
Silvia Stacchiotti
Angelo Paolo Dei Tos
Hans Gelderblom
Stefano Ferrari
Giacomo G. Baldi
Robin L. Jones
Sant Chawla
Paolo Casali
Axel LeCesne
Jean-Yves Blay
Sander P. D. Dijkstra
David M. Thomas
Piotr Rutkowski
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Clinical Sarcoma Research / Issue 1/2016
Electronic ISSN: 2045-3329
DOI
https://doi.org/10.1186/s13569-016-0056-0

Other articles of this Issue 1/2016

Clinical Sarcoma Research 1/2016 Go to the issue

Research

Clinical implications of repeated drug monitoring of imatinib in patients with metastatic gastrointestinal stromal tumour

Research

A Korean single-center, real-world, retrospective study of first-line weekly paclitaxel in patients with metastatic angiosarcoma

Research

Response to anti-PD1 therapy with nivolumab in metastatic sarcomas

Meeting Report

The ENCCA-WP7/EuroSarc/EEC/PROVABES/EURAMOS 3rd European Bone Sarcoma Networking Meeting/Joint Workshop of EU Bone Sarcoma Translational Research Networks; Vienna, Austria, September 24–25, 2015. Workshop Report

Review

UK guidelines for the management of soft tissue sarcomas

Research

High nuclear expression of proteasome activator complex subunit 1 predicts poor survival in soft tissue leiomyosarcomas
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits