Evaluation of Local Recurrence in Giant-Cell Tumor of Bone Treated by Neoadjuvant Denosumab

Abstract

Background Giant-cell tumor of bone (GCTB) is a locally aggressive primary benign tumor presenting as an expansile osteolytic lesion affecting the epiphysis of long bones. Denosumab halts the osteolysis by giant cells thereby downstaging the tumor, helping in performing less morbid procedures to remove the tumor. Our aim was to report the incidence of local recurrence (LR) in patients operated following neoadjuvant denosumab, to investigate factors associated with LR following extended curettage for GCTB, and to compare the postoperative functional and oncological outcome of patients operated with and without neoadjuvant denosumab. Methods A total of 123 patients with a mean age of 29.6 years undergoing extended curettage for GCTB were retrospectively divided into group 1 receiving neoadjuvant denosumab and group 2 operated without denosumab. The mean follow-up period was 35 months. The perioperative characteristics and outcome were compared between the two groups and the factors for LR of GCTB were analyzed. Results The incidence of LR among patients operated after neoadjuvant denosumab therapy was 42.8% and was significantly high compared to that in patients without denosumab ( p < 0.001). On multivariate logistic regression analysis, use of denosumab as a neoadjuvant was the only factor independently associated with LR following surgery ( p = 0.002). Patients treated with denosumab had a lower LR-free survival rate (log-rank, p = 0.018). Conclusions Denosumab was independently associated with increased LR following surgery for GCTB. Denosumab has to be used cautiously in patients in whom the burden of downstaging the disease outweighs the possible chance of LR.

Preoperative Denosumab may increase the Risk of Local Recurrence of Giant-cell Tumor of Bone Treated with Curettage: A Systematic Review and Meta-analysis

“…However, Chen et al [8] indicated a comparable local recurrence rate between preoperative denosumab followed by curettage and curettage-only group in sacral GCTB (3/11, 27.27% versus 3/10, 30.00%). A definite conclusion has yet to be obtained about preoperative denosumab on the local recurrence of GCTB treated with curettage because of contradictory results across published studies [7][8][9][10][11][12][13][14][15]. The current study is a systematic review and meta-analysis that investigates the effect of preoperative denosumab on the local recurrence of GCTB treated with curettage.…”

“…Previous studies indicated that preoperative denosumab could result in beneficial surgical downstaging in the treatment of GCTB [6]. Data from other studies suggested that preoperative denosumab might increase the risk of local recurrence after the curettage of GCTB [7][8][9][10][11][12][13][14][15]. Scoccianti et al [13] evaluated the local recurrence rate of GCTB treated with curettage and cryotherapy, and the authors observed a higher local recurrence rate in preoperative denosumab plus the…”

Image-Guided Percutaneous Management of Skull and Spine Giant Cell Tumors: Case Report of 2 Challenging Cases Successfully Treated with Doxycycline Sclerotherapy

“…However, some studies have shown that these adjuvants, although they possibly facilitate more effective or safe surgery, have limited influence on decreasing the recurrence rate 9 , 18 . Recent studies report that neoadjuvant treatment with denosumab actually increases the risk of recurrence after surgery, making its use for this indication problematic 8 , 9 …”

“…Denosumab was approved by the U.S. Food and Drug Administration for use in the treatment of these surgically challenging GCTs in 2013 6 . Since that time it has been tried as a salvage treatment or a neoadjuvant preoperative measure, but recent reviews indicate that it usually results in only partial response and can in fact increase the risk of postoperative recurrence after later curettage 7, 8, 9…”

Denosumab in Giant Cell Tumor of Bone: Current Status and Pitfalls

“…The authors found that denosumab was the only independent factor relevant to local recurrence by multivariate analysis, although the other two factors, the initial type of treatment and the location of the tumor, played roles on univariate analysis. Chinder et al ( 43 ) conducted a study of 123 patients to evaluate the local recurrence of neoadjuvant denosumab following extensive curettage. This study was well-matched for the site of tumor and the type of surgery.…”