Pre-operative denosumab is associated with higher risk of local recurrence in giant cell tumor of bone: a systematic review and meta-analysis

Chen, Xi; Li, Hairui; Zhu, Shibai; Wang, Yiou; Qian, Wenwei

doi:10.1186/s12891-020-03294-2

Cited by 28 publications

(29 citation statements)

References 31 publications

(82 reference statements)

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“…Thus, prevention of local recurrence is an important part of GCTB treatment. Denosumab, which is a human monoclonal anti-RANKL antibody that inhibits the RANK/RANKL signaling pathway, has been introduced to treat GCTB 12 , 13 , 34 . Pathological findings have previously revealed osteoclast-like multinucleated giant cell and mononuclear stromal cell depletion and new bone formation after denosumab treatment 11 , 35 , 36 .…”

Section: Discussionmentioning

confidence: 99%

“…Kato et al reported that after denosumab therapy, mononuclear tumor cells with H3F3A mutations could survive, but osteoclast cells could not survive without RANK/RANKL signaling 6 . Some reports have recently suggested that preoperative denosumab administration might increase the recurrence rate after operation 34 , 37 . New bone formation may be difficult to distinguish from preexisting bone trabeculae and make it difficult to identify true surgical margins 34 .…”

Section: Discussionmentioning

confidence: 99%

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Tumor microenvironment in giant cell tumor of bone: evaluation of PD-L1 expression and SIRPα infiltration after denosumab treatment

Toda

Kohashi

Yamamoto

et al. 2021

Sci Rep

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Giant cell tumor of bone (GCTB) is an intermediate malignant bone tumor that is locally aggressive and rarely metastasizes. Denosumab, which is a receptor activator of nuclear factor kappa B ligand (RANKL) inhibitor, can be used to treat GCTB. We focused on potential immunotherapy for GCTB and investigated the tumor microenvironment of GCTB. Programmed death-ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) expression and signal-regulatory protein alpha (SIRPα), forkhead box P3 (FOXP3), and cluster of differentiation 8 (CD8) infiltration were assessed by immunohistochemical studies of 137 tumor tissues from 96 patients. Of the naive primary specimens, 28% exhibited PD-L1 expression and 39% exhibited IDO1 expression. There was significantly more SIRPα+, FOXP3+, and CD8+ cell infiltration in PD-L1- and IDO1-positive tumors than in PD-L1- and IDO1-negative tumors. The frequency of PD-L1 expression and SIRPα+ cell infiltration in recurrent lesions treated with denosumab was significantly higher than in primary lesions and recurrent lesions not treated with denosumab. PD-L1 expression and higher SIRPα+ cell infiltration were significantly correlated with shorter recurrence-free survival. PD-L1 and SIRPα immune checkpoint inhibitors may provide clinical benefit in GCTB patients with recurrent lesions after denosumab therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Tumor microenvironment in giant cell tumor of bone: evaluation of PD-L1 expression and SIRPα infiltration after denosumab treatment

Toda

Kohashi

Yamamoto

et al. 2021

Sci Rep

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“…9 In contrast, Denosumab has been shown to increase the chance of leaving residual tumour behind in intralesional surgeries, Hence, it was not used in previous surgeries around the ankle. 10,11 It was tempting for us to consider continuing denosumab therapy after the third instance of the tumour with the hope that subsequent recurrences would be prevented. However, there is no evidence to suggest that denosumab can prevent future lesions in metachronous GCT.…”

Section: Discussionmentioning

confidence: 99%

“…However, there is no evidence to suggest that denosumab can prevent future lesions in metachronous GCT. 10,11 The optimum strategy for surveillance of children with metachronous GCT is a challenge. We can only speculate whether an early diagnosis on screening before the lesion becomes symptomatic can alter the prognosis or the extent of surgery.…”

Section: Discussionmentioning

confidence: 99%

Metachronous multicentric giant cell tumour of bone in a 12-year-old girl: A case report and review of literature

Wadia

Chaudhary

Anchan

et al. 2021

Journal of Orthopaedics, Trauma and Rehabilitation

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While giant cell tumour of bone is a relatively common tumour in adults, it is exceedingly rare in children. Multicentric metachronous giant cell tumour is an even rarer presentation of this tumour in skeletally immature patients. We present here the challenges in management of this rare tumour. A 12-year-old girl presented with a giant cell tumour affecting four different bones sequentially, three times within a 3-year period. The disease first appeared in the right distal fibula, then a year later in ipsilateral talus and calcaneus and finally a year later, in the T5 vertebral body, all requiring surgical treatment. Our strategy was to manage this lesion aggressively based on the limited literature available and present our own long-term surveillance strategy. Our patient responded well to treatment each time and has remained disease-free for 24 months from her last surgery. This is a rare case of metachronous multicentric giant cell tumour of bone in a skeletally immature patient requiring aggressive treatment and surveillance.

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“…The timing and influence of a neoadjuvant treatment with denosumab on recurrence of GCTB is still under investigation. Chen et al reviewed 10 studies with a total of 1082 cases and found an increased risk of local recurrence after preoperative treatment of GCTB with denosumab [ 12 ]. However, in our case, the aim of the denosumab treatment was the downstaging of the tumour to facilitate a joint salvage procedure and therefore a preoperative treatment was imperative.…”

Section: Discussionmentioning

confidence: 99%

The use of denosumab in the setting of acute pathological fracture through giant cell tumour of bone

2021

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Background Denosumab (XgevaTM) is a fully human antibody to RANK-Ligand, an important signal mediator in the pathogenesis of giant cell tumour of bone (GCTB). The use of denosumab in the treatment of GCTB has changed the way in which these tumours are managed over the past years. Case presentation Described is the case of an acute fracture through a GCTB of the distal radius of a fit and well 32-year-old, non-smoking, female patient following a simple fall onto her outstretched, dominant hand. The aim was to enable joint sparing management for the patient, as opposed to an acute fusion procedure of the carpus. The patient underwent percutaneous k-wire fixation with application of plaster and immediate commencement with denosumab to halt the activity of the GCTB. Bone healing was rapid; plaster and k-wires were removed after 6 weeks. At 6 months denosumab, was ceased and an open curettage and grafting procedure of the tumour bed was undertaken (using MIIG X3, Wright Medical, aqueous calcium sulphate as graft material). Conclusions The use of denosumab in the acute setting of pathological fracture through giant cell tumour of bone allowing joint salvage has not been previously described. The treatment was well tolerated and functional outcomes are excellent, with very promising 4-year follow-up. This novel approach may allow for more joint sparing strategies in the future for other patients in this difficult situation. Further cases will need to be gathered to establish this technique as a suitable treatment pathway.

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Pre-operative denosumab is associated with higher risk of local recurrence in giant cell tumor of bone: a systematic review and meta-analysis

Cited by 28 publications

References 31 publications

Tumor microenvironment in giant cell tumor of bone: evaluation of PD-L1 expression and SIRPα infiltration after denosumab treatment

Tumor microenvironment in giant cell tumor of bone: evaluation of PD-L1 expression and SIRPα infiltration after denosumab treatment

Metachronous multicentric giant cell tumour of bone in a 12-year-old girl: A case report and review of literature

The use of denosumab in the setting of acute pathological fracture through giant cell tumour of bone

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