Giant cell tumour of the bone treated with denosumab: How has the blood supply and oncological prognosis of the tumour changed?

Abstract

Background: Denosumab is gradually applied to refractory or unresectable giant cell tumour of the bone. Whether denosumab can effectively reduce the blood supply of tumour and bring benefit is worthy of study. The aim of the study is to evaluate the related changes after treatment: blood supply, surgical plan downstaging, surgical difficulty and oncological prognosis.

Methods: A self-case-control study was performed from June 2014 to November 2016, and 18 patients were enrolled. Patients received subcutaneous denosumab 120 mg every 4 weeks preoperatively, with additional doses administered on Days 8 and 15 during the first month of therapy. The initial treatment duration was 12 weeks. After 12 weeks treatment, enhanced CT examination was performed for evaluating whether surgical treatment was practicable. The patients received preoperative denosumab treatment for 5 (median 3, range 3-12) months in average. The microvessel density of tumour samples was calculated for evaluating tumour blood supply. The computed tomography (CT) enhancement rate was compared before and after treatment. The related changes of parameters were recorded as the following: clinical benefits, serious side effects, enhancement rate of CT, surgical plans, intraoperative blood loss, operative time, surgical difficulty, histological changes and local recurrence. The patients were followed up every 3 months postoperatively.

Results: The average CT enhancement rate of lesions was 2.08 and 1.40 before and after treatment (p = 0.000), respectively. The unenhanced CT value was significantly increased after treatment (p = 0.038). The CT enhancement rate changed more significantly in pelvic or sacral lesions than that in limb lesions (p = 0.024). Sixteen cases underwent final surgery, and surgical plan was downstaged. The histological examination showed tumour cells were significantly reduced or even disappeared after treatment. The microvessel density decreased significantly after treatment. The mean postoperative follow-up was 18.8 (10-31) months, and five patients had local recurrence. The high local recurrence rate (4/6) in sacral tumours may be related to the increased difficulty of curettage.

Conclusion: Denosumab treatment can reduce the blood supply of giant cell tumour. The sacral or pelvic lesions changed more significantly than limb lesions. The surgical plan downstaging can also be achieved. The clear margin after denosumab treatment facilitated tumour resection but, increased difficult in curettage surgery, and high recurrence rate of sacral tumour is being concerned.

The translational impact of this article: Denosumab is a new type of humanized monoclonal antibody which showed some effect in the treatment giant cell tumor of bone. Pre-operative treatment with denosamub can reduce intra-operative blood loss and down-stage surgical plan in suitable cases.

Keywords: Blood supply; Denosumab; Giant cell tumour of bone; Prognosis; Surgical treatment.

Figure 1

The HE staining of tumour tissue before denosumab treatment showed typical histological features of GCTB; (B) the osteoclast-like giant cells almost disappeared and mononuclears decreased significantly after treatment. GCTB = giant cell tumour of bone, HE = hematoxylin-eosin after GCTB.

Figure 2

The CT scan showed the significant changing of sacral giant cell tumour before and after treatment in the same lesion. The unenhanced CT (A) and enhanced CT (C) before treatment showed significant enhancement of lesion. The unenhanced CT (B) and enhanced CT (D) after treatment showed the increasing of sclerosis and new bone formation, and also the decreasing of enhancement. CT = computed tomography.

Figure 3

The histopathological changing after treatment. Before treatment (A 40×, B 100× and C 200×): the lesion was full of mononuclears and osteoclast-like giant cells; CD34 antibody showed significant expression of MVD. After treatment (D 40×, E 100× and F 200×): the osteoclast-like giant cells almost disappeared and mononuclears decreased significantly; CD34 antibody showed significantly decreased expression of MVD. MVD = microvessel density.

Figure 4

The changing of enhancement rate of lesion before and after treatment (each point corresponds to enhancement rate in each patient). CT = computed tomography.

Figure 5

The compartment of changing of enhancement rate of lesion and vascular before and after treatment. CT = computed tomography.

Figure 6

The compartment of enhancement rate of the sacral or pelvic lesion and limb lesion before and after treatment. CT = computed tomography.

Figure 7

The patient with tumour recurrence of the distal ulna received preoperative denosumab treatment and tumour resection. The recurrence tumours were not clearly shown before treatment (A) and the tumour ranges were clearly showed after treatment (B). The multiple lesions were marked before operation (C), and then all visible lesions were excised (D).

Figure 8

Tumour relapsed and progressed after discontinued treatment of denosumab. Multiple extensive soft tissue recurrence was found after operation (A), and amputation was performed (B). The lung metastases showed significant progression after discontinued treatment of denosumab: chest CT before operation (C), 1 month postoperative (D), 6 months postoperative (E) and 9 months postoperative (F). CT = computed tomography.