Skip to main content
Top
Published in: World Journal of Surgical Oncology 1/2016

Open Access 01-12-2016 | Research

Risks and benefits of combining denosumab and surgery in giant cell tumor of bone—a case series

Authors: Daniel A. Müller, Giovanni Beltrami, Guido Scoccianti, Domenico A. Campanacci, Alessandro Franchi, Rodolfo Capanna

Published in: World Journal of Surgical Oncology | Issue 1/2016

Login to get access

Abstract

Background

The RANK ligand inhibitor denosumab is being investigated for treatment of giant cell tumor of bone, but the available data in the literature remains sparse and controversial. This study analyzes the results of combining denosumab with surgical treatment and highlights possible changes for the oncologic surgeon in daily practice.

Methods

A total of 91 patients were treated surgically for giant cell tumor of bone between 2010 and 2014 in an institution, whereas 25 patients of the total additionally received denosumab and were part of this study. The average age of the patients was 35 years. Eleven patients received denosumab pre- and postoperatively, whereas with 14 patients, the denosumab treatment was applied either before (7 patients) or after (7 patients) the surgery. The average preoperative therapy duration was 3.9 months and the postoperative therapy 6 months by default.

Results

Sixteen patients presented a large tumor extension necessitating a resection of the involved bone or joint. In 10 of these patients, the indication for a resection procedure was abandoned due to the preoperative denosumab treatment and a curettage was performed. In the remaining six cases, the surgical indication was not changed despite the denosumab treatment, and two of them needed a joint replacement after the tumor resection. Also with patients treated with curettage, denosumab seems to facilitate the procedure as a new peripheral bone rim around the tumor was built, though a histologic analysis reveals viable tumor cells persisting in the denosumab-induced bone formation.
After an average follow-up of 23 months, one histologically proven local recurrence occurred, necessitating a second curettage. A second patient showed a lesion in the postoperative imaging highly suspicious for local relapse which remained stable under further denosumab treatment. No adverse effect of the denosumab medication was observed in this study.

Conclusions

Denosumab can be a help to the oncologic surgeon by reconstituting a peripheral rim and switching the stage from aggressive to active or latent disease. But as tumor cells remain in the new-formed bone, the surgical technique of curettage has to be changed from gentle to more aggressive to avoid higher local recurrence rates.
Literature
1.
go back to reference Picci PM, Manfrini M, Fabbri N, Gambarotti M, Vanel D. Atlas of musculoskeletal tumors and tumorlike lesions. 1 edn. Cham Heidelberg Dordrecht London New York: Springer International Publishing; 2014. Picci PM, Manfrini M, Fabbri N, Gambarotti M, Vanel D. Atlas of musculoskeletal tumors and tumorlike lesions. 1 edn. Cham Heidelberg Dordrecht London New York: Springer International Publishing; 2014.
3.
go back to reference Resnick D, Kyriakos M, Greenway GD. Tumors and tumor-like lesions of bone: imaging and pathology of specific lesions. Diagnosis of bone and jointdisorders. 3rd ed. Philadelphia: Saunders; 1995. p. 3628-3938 Resnick D, Kyriakos M, Greenway GD. Tumors and tumor-like lesions of bone: imaging and pathology of specific lesions. Diagnosis of bone and jointdisorders. 3rd ed. Philadelphia: Saunders; 1995. p. 3628-3938
4.
go back to reference Siebenrock KA, Unni KK, Rock MG. Giant-cell tumour of bone metastasising to the lungs. A long-term follow-up. J Bone Joint Surg Br. 1998;80:43–7.CrossRefPubMed Siebenrock KA, Unni KK, Rock MG. Giant-cell tumour of bone metastasising to the lungs. A long-term follow-up. J Bone Joint Surg Br. 1998;80:43–7.CrossRefPubMed
5.
6.
go back to reference Skubitz KM. Giant cell tumor of bone: current treatment options. Curr Treat Options Oncol. 2014;15:507–18.CrossRefPubMed Skubitz KM. Giant cell tumor of bone: current treatment options. Curr Treat Options Oncol. 2014;15:507–18.CrossRefPubMed
7.
go back to reference Szendroi M. Giant-cell tumour of bone. J Bone Joint Surg Br. 2004;86:5–12.PubMed Szendroi M. Giant-cell tumour of bone. J Bone Joint Surg Br. 2004;86:5–12.PubMed
8.
go back to reference Enneking WF, Dunham W, Gebhardt MC, Malawar M, Pritchard DJ. A system for the functional evaluation of reconstructive procedures after surgical treatment of tumors of the musculoskeletal system. Clin Orthop Relat Res 1993;286:241–246. Enneking WF, Dunham W, Gebhardt MC, Malawar M, Pritchard DJ. A system for the functional evaluation of reconstructive procedures after surgical treatment of tumors of the musculoskeletal system. Clin Orthop Relat Res 1993;286:241–246.
9.
go back to reference McClung MR, Lewiecki EM, Cohen SB, Bolognese MA, Woodson GC, Moffett AH, et al. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med. 2006;354:821–31.CrossRefPubMed McClung MR, Lewiecki EM, Cohen SB, Bolognese MA, Woodson GC, Moffett AH, et al. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med. 2006;354:821–31.CrossRefPubMed
11.
go back to reference Steensma MR, Tyler WK, Shaber AG, Goldring SR, Ross FP, Williams BO, et al. Targeting the giant cell tumor stromal cell: functional characterization and a novel therapeutic strategy. PLoS One. 2013;8:e69101.CrossRefPubMedPubMedCentral Steensma MR, Tyler WK, Shaber AG, Goldring SR, Ross FP, Williams BO, et al. Targeting the giant cell tumor stromal cell: functional characterization and a novel therapeutic strategy. PLoS One. 2013;8:e69101.CrossRefPubMedPubMedCentral
12.
go back to reference Kim Y, Nizami S, Goto H, Lee FY. Modern interpretation of giant cell tumor of bone: predominantly osteoclastogenic stromal tumor. Clin Orthop Surg. 2012;4:107–16.CrossRefPubMedPubMedCentral Kim Y, Nizami S, Goto H, Lee FY. Modern interpretation of giant cell tumor of bone: predominantly osteoclastogenic stromal tumor. Clin Orthop Surg. 2012;4:107–16.CrossRefPubMedPubMedCentral
13.
go back to reference Thomas D, Henshaw R, Skubitz K, Chawla S, Staddon A, Blay JY, et al. Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Lancet Oncol. 2010;11:275–80.CrossRefPubMed Thomas D, Henshaw R, Skubitz K, Chawla S, Staddon A, Blay JY, et al. Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Lancet Oncol. 2010;11:275–80.CrossRefPubMed
14.
go back to reference Rutkowski P, Ferrari S, Grimer RJ, Stalley PD, Dijkstra SP, Pienkowski A, et al. Surgical downstaging in an open-label phase II trial of denosumab in patients with giant cell tumor of bone. Ann Surg Oncol. 2015;22:2860–8.CrossRefPubMedPubMedCentral Rutkowski P, Ferrari S, Grimer RJ, Stalley PD, Dijkstra SP, Pienkowski A, et al. Surgical downstaging in an open-label phase II trial of denosumab in patients with giant cell tumor of bone. Ann Surg Oncol. 2015;22:2860–8.CrossRefPubMedPubMedCentral
15.
go back to reference Enneking WF. A system of staging musculoskeletal neoplasms. Clin Orthop Relat Res 1986;204:9–24. Enneking WF. A system of staging musculoskeletal neoplasms. Clin Orthop Relat Res 1986;204:9–24.
16.
go back to reference Girolami I, Mancini I, Simoni A, Baldi GG, Simi L, Campanacci D, et al. Denosumab treated giant cell tumour of bone: a morphological, immunohistochemical and molecular analysis of a series. J Clin Pathol. 2016;69:240–7.CrossRefPubMed Girolami I, Mancini I, Simoni A, Baldi GG, Simi L, Campanacci D, et al. Denosumab treated giant cell tumour of bone: a morphological, immunohistochemical and molecular analysis of a series. J Clin Pathol. 2016;69:240–7.CrossRefPubMed
17.
go back to reference Gaston CL, Bhumbra R, Watanuki M, Abudu AT, Carter SR, Jeys LM, 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;93:1665–9.CrossRefPubMed Gaston CL, Bhumbra R, Watanuki M, Abudu AT, Carter SR, Jeys LM, 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;93:1665–9.CrossRefPubMed
18.
go back to reference Gortzak Y, Kandel R, Deheshi B, Werier J, Turcotte RE, Ferguson PC, et al. An in vitro study. J Bone Joint Surg Br. 2010;92:1475–9.CrossRefPubMed Gortzak Y, Kandel R, Deheshi B, Werier J, Turcotte RE, Ferguson PC, et al. An in vitro study. J Bone Joint Surg Br. 2010;92:1475–9.CrossRefPubMed
19.
go back to reference Malawer MM, Bickels J, Meller I, Buch RG, Henshaw RM, Kollender Y. Cryosurgery in the treatment of giant cell tumor. A long-term followup study. Clin Orthop Relat Res 1999;359:176–188. Malawer MM, Bickels J, Meller I, Buch RG, Henshaw RM, Kollender Y. Cryosurgery in the treatment of giant cell tumor. A long-term followup study. Clin Orthop Relat Res 1999;359:176–188.
20.
go back to reference van der Heijden L, Dijkstra PD, van de Sande MA, Kroep JR, Nout RA, van Rijswijk CS, et al. The clinical approach toward giant cell tumor of bone. Oncologist. 2014;19:550–61.CrossRefPubMedPubMedCentral van der Heijden L, Dijkstra PD, van de Sande MA, Kroep JR, Nout RA, van Rijswijk CS, et al. The clinical approach toward giant cell tumor of bone. Oncologist. 2014;19:550–61.CrossRefPubMedPubMedCentral
21.
go back to reference Chawla S, Henshaw R, Seeger L, Choy E, Blay JY, Ferrari S, 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 Chawla S, Henshaw R, Seeger L, Choy E, Blay JY, Ferrari S, 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
Metadata
Title
Risks and benefits of combining denosumab and surgery in giant cell tumor of bone—a case series
Authors
Daniel A. Müller
Giovanni Beltrami
Guido Scoccianti
Domenico A. Campanacci
Alessandro Franchi
Rodolfo Capanna
Publication date
01-12-2016
Publisher
BioMed Central
Published in
World Journal of Surgical Oncology / Issue 1/2016
Electronic ISSN: 1477-7819
DOI
https://doi.org/10.1186/s12957-016-1034-y

Other articles of this Issue 1/2016

World Journal of Surgical Oncology 1/2016 Go to the issue