Abstract:BACKGROUND: Tumor protein p63 (p63) has been reported to be highly expressed in giant cell tumor of bone (GCTB). Whether p63 can be treated as a diagnostic marker for GCTB remains unclear. OBJECTIVE: We conducted a meta-analysis to evaluate the applicability of p63 in diagnosing GCTB. DESIGN AND SETTING: Systematic review and meta-analysis carried out in a public hospital, Hong Kong, China. METHODS: We searched PubMed, EMBASE and the Cochrane Library from inception to April 30, 2019. Literature in English or C… Show more
“…Both groups suggested using these biological markers for character assessment of bone neoplasms and to predict higher recurrence risks in PD-L1 expressing GCTB patients. Also, PD-L1 immune checkpoint inhibitors may be of clinical benefit for recurrent GCTB after denosumab [22 ▪▪ ].…”
Section: Diagnostics and Translational Researchmentioning
Purpose of reviewGiant cell tumors of bone (GCTB) are intermediate, locally aggressive primary bone tumors. For conventional GCTB, surgery remains treatment of choice. For advanced GCTB, a more important role came into play for systemic therapy including denosumab and bisphosphonates over the last decade.Recent findingsIn diagnostics, focus has been on H3F3A (G34) driver mutations present in GCTB. The most frequent mutation (G34W) can be detected using immunohistochemistry and is highly specific in differentiating GCTB from other giant cell containing tumors. PD-L1 expression can be used as biological marker to predict higher recurrence risks in GCTB patients.The use of bisphosphonate-loaded bone cement is under investigation in a randomized controlled trial. A new technique consisting of percutaneous microwave ablation and bisphosphonate-loaded polymethylmethacrylate cementoplasty was proposed for unresectable (pelvic) GCTB.Increased experience with use of denosumab raised concern on elevated recurrence rates. However, conclusions of meta-analyses should be interpreted with risk of indication bias in mind. Several small studies are published with short-course denosumab (varying from 3 to 6 doses). One small trial directly compared denosumab and zoledronic acid, with no statistical differences in radiological and clinical outcome, and nonsignificantly higher recurrence rate after denosumab. As bisphosphonates directly target neoplastic stromal cells in GCTB, larger directly comparative trials are still warranted.SummaryNeoadjuvant denosumab is highly effective for advanced GCTB, and a short-course is advised to facilitate surgery, whereas increased recurrence rates remain of concern. Randomized controlled trials are conducted on bisphosphonate-loaded bone cement and on optimal dose and duration of neoadjuvant denosumab. PD-L1 could be a potential new therapy target in GCTB.
“…Both groups suggested using these biological markers for character assessment of bone neoplasms and to predict higher recurrence risks in PD-L1 expressing GCTB patients. Also, PD-L1 immune checkpoint inhibitors may be of clinical benefit for recurrent GCTB after denosumab [22 ▪▪ ].…”
Section: Diagnostics and Translational Researchmentioning
Purpose of reviewGiant cell tumors of bone (GCTB) are intermediate, locally aggressive primary bone tumors. For conventional GCTB, surgery remains treatment of choice. For advanced GCTB, a more important role came into play for systemic therapy including denosumab and bisphosphonates over the last decade.Recent findingsIn diagnostics, focus has been on H3F3A (G34) driver mutations present in GCTB. The most frequent mutation (G34W) can be detected using immunohistochemistry and is highly specific in differentiating GCTB from other giant cell containing tumors. PD-L1 expression can be used as biological marker to predict higher recurrence risks in GCTB patients.The use of bisphosphonate-loaded bone cement is under investigation in a randomized controlled trial. A new technique consisting of percutaneous microwave ablation and bisphosphonate-loaded polymethylmethacrylate cementoplasty was proposed for unresectable (pelvic) GCTB.Increased experience with use of denosumab raised concern on elevated recurrence rates. However, conclusions of meta-analyses should be interpreted with risk of indication bias in mind. Several small studies are published with short-course denosumab (varying from 3 to 6 doses). One small trial directly compared denosumab and zoledronic acid, with no statistical differences in radiological and clinical outcome, and nonsignificantly higher recurrence rate after denosumab. As bisphosphonates directly target neoplastic stromal cells in GCTB, larger directly comparative trials are still warranted.SummaryNeoadjuvant denosumab is highly effective for advanced GCTB, and a short-course is advised to facilitate surgery, whereas increased recurrence rates remain of concern. Randomized controlled trials are conducted on bisphosphonate-loaded bone cement and on optimal dose and duration of neoadjuvant denosumab. PD-L1 could be a potential new therapy target in GCTB.
“…p63 has also been shown to be highly expressed in GCTB mononuclear neoplastic cells [65][66][67], but its usefulness is still to be determined. A meta-analysis of eight different studies including 335 GCTB patients showed that p63 is a helpful marker for GCTB diagnosis in critically ill patients, although it cannot be recommended as a single definitive diagnostic marker [68]. Finally, it has been suggested that high RANKL, IL-6, TNFα, SDF-1, and MCP-1 expression may help predict GCTB metastatic potential and prognosis, warranting further studies [69].…”
Giant cell tumor of bone (GCTB) is mostly a benign disease of the bone, although with high local recurrence rate and potential for metastatic spread, namely to the lungs. It is also a locally aggressive tumor, associated with severe morbidity and functional impairment due to bone destruction. Treatment is therefore required and should be offered at an early stage to allow complete resection, minimizing functional sequelae and local recurrence. Surgical resection is the mainstay of treatment, often followed by intralesional adjuvant therapy. GCTB has a particular biology, in which RANKL represents a key factor in tumor pathogenesis, thus making this molecule a valuable therapeutic target. Monthly administration of denosumab, a fully human monoclonal antibody directed against RANKL, has been studied in several clinical trials and shown a high rate of local control with favorable safety profile. In this chapter, current medical management, ongoing studies, and future directions in GCTB will be discussed.
Highlights
Characteristics of 62 patients with spinal GCTB who underwent surgery.
A prognostic classification model was built based on features selected by SVM.
The combined histogram and texture features could predict recurrence of GCTB.
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