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.