Updated concepts in treatment of giant cell tumor of bone

Abstract

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.

Giant cell tumor of the bone: an evaluation of prognostic factors associated with local recurrence and a comparison with the current literature

“…Randomized controlled trials are conducted on bisphosphonate-loaded bone cement and on optimal dose and duration of neoadjuvant denosumab (29). There are studies that say that denosumab and zoledronic acid have similar tumor responses and clinical benefits.…”

Progress on Denosumab Use in Giant Cell Tumor of Bone: Dose and Duration of Therapy

“…For advanced or inoperable GCTB, the usual dose utilized is 120 mg monthly administered by subcutaneous injection, followed by an additional dose on days 8 and 15 after the first dose. Calcium and vitamin D should be concomitantly given for at least 6 months [ 61 ]. Several multicenter phase II clinical trials for advanced or inoperable GCTB have been completed and show a definite short-term efficacy [ 62 , 63 ].…”

A technical note on autologous iliac crest bone grafting for restoration of the distal tibial articular surface

“…Giant cell tumor of bone (GCTB) is a benign locally aggressive tumor representing 5% of all primary bone tumors [ 22 ]. This tumor rarely metastasizes, but it has a high tendency for local recurrence [ 10 , 20 ].…”

“…Treatment of GCTB should aim for local control without sacrificing joint function [ 9 , 21 ]. The functional preserving surgery for GCTB is extended curettage with high-speed burring and chemical adjuvants such as liquid nitrogen, alcohol, or phenol and filling the resulting cavity with polymethylmethacrylate (PMMA) bone cement, bone substitutes, or bone graft [ 9 , 18 , 20 ].…”

“…In advanced cases where joint salvage is not feasible, en-bloc resection and endoprosthetic reconstruction may be an option but may result in increased morbidity and unfavorable functional outcomes in GCTB patients, who are frequently young and active [11,19].…”