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Tsun Cheung Chow

Bio: Tsun Cheung Chow is an academic researcher. The author has contributed to research in topics: Giant-cell tumor of bone & Bisphosphonate. The author has an hindex of 1, co-authored 1 publications receiving 174 citations.

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Journal ArticleDOI
01 Jan 2008-Bone
TL;DR: Clinical use of bisphosphonates as an adjuvant therapy for giant cell tumor of bone demonstrated a lower local recurrence rate and the clinical response seems to be more promising in stage III diseases.

192 citations


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Journal ArticleDOI
TL;DR: In this article, the potential therapeutic effect of denosumab, a fully human monoclonal antibody against RANKL, on tumour-cell survival and growth in patients with GCT was investigated.
Abstract: Summary Background Giant-cell tumour (GCT) of bone is a primary osteolytic bone tumour with low metastatic potential and is associated with substantial skeletal morbidity. GCT is rich in osteoclast-like giant cells and contains mononuclear (stromal) cells that express RANK ligand (RANKL), a key mediator of osteoclast activation. We investigated the potential therapeutic effect of denosumab, a fully human monoclonal antibody against RANKL, on tumour-cell survival and growth in patients with GCT. Methods In this open-label, single-group study, 37 patients with recurrent or unresectable GCT were enrolled and received subcutaneous denosumab 120 mg monthly (every 28 days), with loading doses on days 8 and 15 of month 1. The primary endpoint was tumour response, defined as elimination of at least 90% of giant cells or no radiological progression of the target lesion up to week 25. Study recruitment is closed; patient treatment and follow-up are ongoing. The study is registered with Clinical Trials.gov, NCT00396279. Findings Two patients had insufficient histology or radiology data for efficacy assessment. 30 of 35 (86%; 95% CI 70–95) of evaluable patients had a tumour response: 20 of 20 assessed by histology and 10 of 15 assessed by radiology. Adverse events were reported in 33 of 37 patients; the most common being pain in an extremity (n=7), back pain (n=4), and headache (n=4). Five patients had grade 3–5 adverse events, only one of which (grade 3 increase in human chorionic gonadotropin concentration not related to pregnancy) was deemed to be possibly treatment related. Five serious adverse events were reported although none were deemed treatment related. Interpretation Further investigation of denosumab as a therapy for GCT is warranted. Funding Amgen, Inc.

575 citations

Journal ArticleDOI
TL;DR: Denosumab treatment of patients with GCTB significantly reduced or eliminated RANK-positive tumor giant cells and reduced the relative content of proliferative, densely cellular tumor stromal cells, replacing them with nonproliferative, differentiated, densely woven new bone.
Abstract: Purpose: Giant cell tumor of bone (GCTB) is a locally aggressive, benign osteolytic tumor in which bone destruction is mediated by RANKL. The RANKL inhibitor denosumab is being investigated for treatment of GCTB. We describe histologic analyses of GCTB tumor samples from a phase 2 study of denosumab in GCTB. Experimental Design: Adult patients with recurrent or unresectable GCTB received subcutaneous denosumab 120 mg every 4 weeks (with additional doses on days 8 and 15). The primary histologic efficacy endpoint was the proportion of patients who had a ≥ 90% elimination of giant cells from their tumor. Baseline and on-study specimens were also evaluated for overall tumor morphology and expression of RANK and RANKL. Results: Baseline tumor samples were typically composed of densely cellular proliferative RANKL-positive tumor stromal cells, RANK-positive rounded mononuclear cells, abundant RANK-positive tumor giant cells, and areas of scant de novo osteoid matrix and woven bone. In on-study samples from 20 of 20 patients (100%), a decrease of ≥ 90% in tumor giant cells and a reduction in tumor stromal cells were observed. In these analyses, thirteen patients (65%) had an increased proportion of dense fibro-osseous tissue and/or new woven bone, replacing areas of proliferative RANKL positive stromal cells. Conclusions: Denosumab treatment of patients with GCTB significantly reduced or eliminated RANK-positive tumor giant cells. Denosumab also reduced the relative content of proliferative, densely cellular tumor stromal cells, replacing them with non-proliferative, differentiated, densely woven new bone. Denosumab continues to be studied as a potential treatment for GCTB.

368 citations

Journal ArticleDOI
TL;DR: This work considers how osteoclast signals may contribute to bone formation by osteoblasts and to the pathology of bone lesions such as fibrous dysplasia and giant cell tumors and reviews the interaction of osteoclasts with the hematopoietic system, including the stem cell niche and adaptive immune cells.

302 citations

Journal ArticleDOI
TL;DR: Intralesional surgery with polymethylmethacrylate is recommended for the majority of primary GCTs and the potential for metastases should not by itself create an indication for wide resection of primary tumors.
Abstract: Background Many surgeons treat giant cell tumor of bone (GCT) with intralesional curettage. Wide resection is reserved for extensive bone destruction where joint preservation is impossible or when expendable sites (eg, fibular head) are affected. Adjuvants such as polymethylmethacrylate and phenol have been recommended to reduce the risk of local recurrence after intralesional surgery. However, the best treatment of these tumors and risk factors for recurrence remain controversial.

299 citations

Journal ArticleDOI
TL;DR: Osteonecrosis of the jaws incidence correlation with BP potency suggests that inhibition of osteoclast function and differentiation might be a key factor in the pathophysiology of the disease.

242 citations