Clinical, radiological and pathological outcomes following treatment of primary giant cell tumour of bone with Denosumab.
Denosumab
giant cell tumour
Journal
ANZ journal of surgery
ISSN: 1445-2197
Titre abrégé: ANZ J Surg
Pays: Australia
ID NLM: 101086634
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
13
05
2020
revised:
27
06
2020
accepted:
05
07
2020
pubmed:
9
8
2020
medline:
15
5
2021
entrez:
9
8
2020
Statut:
ppublish
Résumé
Giant cell tumour of bone (GCTOB) is a relatively uncommon, benign, but locally aggressive neoplasm. Denosumab is a fully human monoclonal antibody with inhibitory effects on receptor activator of nuclear factor kappa-B ligand that has shown early promise as a possible treatment adjuvant for GCTB. However, much is still unknown about its current indications, long-term effects, the potential risk for rapid relapse and its involvement in sarcomatous transformation. We analysed the outcomes of 154 patients with GCTOB. We assessed clinical outcomes via local recurrence free-survival, metastatic free-survival and sarcomatous transformation between those treated without Denosumab and those with neo-adjuvant Denosumab. Our radiological and pathological outcomes were assessed through independent specialist reviews. Four (19.0%) patients of the neo-adjuvant group had local recurrence of disease versus 16 (12.0%) patients in the surgery alone group; this results in a 3.62 times increased likelihood of developing local recurrence (P = 0.030). The median time to local recurrence was shorter for the neo-adjuvant group (421.5 days versus 788.5 days) (P = 0.01). There was no difference between Denosumab and the surgery groups in terms of metastatic disease (P = 0.45). Two patients in our cohort with GCTOB developed sarcomatous transformation, both were treated with Denosumab. Our use of Denosumab tended to be for those patients who had surgically difficult tumours to halt the progression and allow easier resections. Of concern we noted a trend towards increasing recurrence rates with the potential risk for rapid relapse. Furthermore, two cases experienced sarcomatous transformation, which is a growing area of concern within the literature.
Sections du résumé
BACKGROUND
Giant cell tumour of bone (GCTOB) is a relatively uncommon, benign, but locally aggressive neoplasm. Denosumab is a fully human monoclonal antibody with inhibitory effects on receptor activator of nuclear factor kappa-B ligand that has shown early promise as a possible treatment adjuvant for GCTB. However, much is still unknown about its current indications, long-term effects, the potential risk for rapid relapse and its involvement in sarcomatous transformation.
METHODS
We analysed the outcomes of 154 patients with GCTOB. We assessed clinical outcomes via local recurrence free-survival, metastatic free-survival and sarcomatous transformation between those treated without Denosumab and those with neo-adjuvant Denosumab. Our radiological and pathological outcomes were assessed through independent specialist reviews.
RESULTS
Four (19.0%) patients of the neo-adjuvant group had local recurrence of disease versus 16 (12.0%) patients in the surgery alone group; this results in a 3.62 times increased likelihood of developing local recurrence (P = 0.030). The median time to local recurrence was shorter for the neo-adjuvant group (421.5 days versus 788.5 days) (P = 0.01). There was no difference between Denosumab and the surgery groups in terms of metastatic disease (P = 0.45). Two patients in our cohort with GCTOB developed sarcomatous transformation, both were treated with Denosumab.
CONCLUSION
Our use of Denosumab tended to be for those patients who had surgically difficult tumours to halt the progression and allow easier resections. Of concern we noted a trend towards increasing recurrence rates with the potential risk for rapid relapse. Furthermore, two cases experienced sarcomatous transformation, which is a growing area of concern within the literature.
Substances chimiques
Bone Density Conservation Agents
0
Denosumab
4EQZ6YO2HI
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2553-2558Informations de copyright
© 2020 Royal Australasian College of Surgeons.
Références
Thomas DM, Skubitz KM. Giant cell tumour of bone. Curr. Opin. Oncol. 2009; 21: 338-44.
Hakozaki M, Tajino T, Yamada H et al. Radiological and pathological characteristics of giant cell tumor of bone treated with denosumab. Diagn. Pathol. 2014; 9: 111.
Campanacci M, Baldini N, Boriani S, Sudanese A. Giant-cell tumor of bone. J. Bone Joint Surg. Am. 1987; 69: 106-14.
Szendroi M. Giant-cell tumour of bone. J. Bone Joint Surg. Br. 2004; 86: 5-12.
Luengo-Alonso G, Mellado-Romero M, Shemesh S, Ramos-Pascua L, Pretell-Mazzini J. Denosumab treatment for giant-cell tumor of bone: a systematic review of the literature. Arch. Orthop. Trauma Surg. 2019; 139: 1339-49.
Sobti A, Agrawal P, Agarwala S, Agarwal M. Giant cell tumor of bone - an overview. Arch. Bone Joint Surg. 2016; 4: 2-9.
Thornley P, Habib A, Bozzo A, Evaniew N, Ghert M. The role of denosumab in the modern treatment of giant cell tumor of bone. JBJS Rev. 2017; 5: e4.
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.
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.
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.
Thomas DM. RANKL, denosumab, and giant cell tumor of bone. Curr. Opin. Oncol. 2012; 24: 397-403.
Jamshidi K, Gharehdaghi M, Hajialiloo SS, Mirkazemi M, Ghaffarzadehgan K, Izanloo A. Denosumab in patients with giant cell tumor and its recurrence: a systematic review. Arch. Bone Joint Surg. 2018; 6: 260-8.
Rutkowski P, Ferrari S, Grimer RJ 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.
Ueda T, Morioka H, Nishida Y et al. Objective tumor response to denosumab in patients with giant cell tumor of bone: a multicenter phase II trial. Ann. Oncol. 2015; 26: 2149-54.
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.
Gaston CL, Grimer RJ. Current status and unanswered questions on the use of denosumab in giant cell tumor of bone. Clin. Sarcoma Res. 2016; 6: 15.
Watanabe N, Matsumoto S, Shimoji T et al. 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.
Müller DA, Beltrami G, Scoccianti G, Campanacci DA, Franchi A, Capanna R. Risks and benefits of combining denosumab and surgery in giant cell tumor of bone-a case series. World J. Surg. Oncol. 2016; 14: 281.
Errani C, Tsukamoto S, Leone G et al. Denosumab may increase the risk of local recurrence in patients with giant-cell tumor of bone treated with curettage. J. Bone Joint Surg. Am. 2018; 100: 496-504.
Matcuk GR Jr, Patel DB, Schein AJ, White EA, Menendez LR. Giant cell tumor: rapid recurrence after cessation of long-term denosumab therapy. Skeletal Radiol. 2015; 44: 1027-31.
Brodowicz T, Hemetsberger M, Windhager R. Denosumab for the treatment of giant cell tumor of the bone. Future Oncol. 2015; 11: 1881-94.
Roitman PD, Jauk F, Farfalli GL, Albergo JI, Aponte-Tinao LA. Denosumab-treated giant cell tumor of bone. Its histologic spectrum and potential diagnostic pitfalls. Hum. Pathol. 2017; 63: 89-97.
Wojcik J, Rosenberg AE, Bredella MA et al. Denosumab-treated giant cell tumor of bone exhibits morphologic overlap with malignant giant cell tumor of bone. Am. J. Surg. Pathol. 2016; 40: 72-80.
Goldschlager T, Dea N, Boyd M et al. Giant cell tumors of the spine: has denosumab changed the treatment paradigm? J. Neurosurg. Spine 2015; 22: 526-33.
Dubory A, Missenard G, Domont J, Court C. Interest of denosumab for the treatment of giant-cells tumors and aneurysmal bone cysts of the spine. About nine cases. Spine 2016; 41: E654-60.
Traub F, Singh J, Dickson BC et al. Efficacy of denosumab in joint preservation for patients with giant cell tumour of the bone. Eur. J. Cancer 2016; 59: 1-12.
Palmerini E, Chawla NS, Ferrari S et al. Denosumab in advanced/unresectable giant-cell tumour of bone (GCTB): for how long? Eur. J. Cancer 2017; 76: 118-24.
Boye K, Jebsen NL, Zaikova O et al. Denosumab in patients with giant-cell tumor of bone in Norway: results from a nationwide cohort. Acta Oncol. 2017; 56: 479-83.
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: 3050-5.
Broehm CJ, Garbrecht EL, Wood J, Bocklage T. Two cases of sarcoma arising in giant cell tumor of bone treated with denosumab. Case Rep. Med. 2015; 2015: 767198.