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Denosumab in Giant Cell Tumor of Bone: Current Status and Pitfalls
Hengyuan Li1,2, Junjie Gao2,3, Youshui Gao3
1Department of Orthopedics, Centre for Orthopedic Research, School of Medicine, Orthopedics Research Institute, Second Affiliated Hospital, Zhejiang University, Hangzhou, China.
Abstract:
Denosumab is a monoclonal antibody against RANK ligand for treatment of giant cell tumor of bone (GCTB). Clinical trials and case series have demonstrated that denosumab is relevant to beneficial tumor response and surgical down-staging in patients of GCTB. However, these trials or case series have limitations with a short follow-up. Recent increasing studies revealed that denosumab probably increased the local recurrence risk in patients treated with curettage. This may be caused by the thicken bone margin of tumor that trapped tumor cells from curettage. The direct bone formation by tumor cells in the margin after denosumab treatment also contributed to the local recurrence. in vitro studies showed denosumab resulted in a cytostatic instead of a true cytotoxic response on neoplastic stromal cells. More importantly, denosumab-treated GCTB exhibited morphologic overlap with malignancy, and a growing number of patients of malignant transformation of GCTB during denosumab treatment have been reported. The optimal duration, long term safety, maintenance dose, and optimum indications remain to be elucidated. With these concerns in mind, this review warns that the denosumab therapy of GCTB should be applied with caution.
Insights
Denosumab shows benefits for giant cell tumor of bone (GCTB) but may increase recurrence risk and lead to malignant transformation. Caution is advised for its use in GCTB treatment.
Area of Science:
- Oncology
- Orthopedic Surgery
- Pharmacology
Background:
- Denosumab, a monoclonal antibody targeting RANK ligand, is used for giant cell tumor of bone (GCTB).
- Previous studies indicated positive tumor response and surgical down-staging benefits.
- Limited follow-up periods in prior research necessitate further investigation into long-term effects.
Purpose of the Study:
- To review the efficacy and safety of denosumab in GCTB treatment.
- To highlight potential risks associated with denosumab therapy, including local recurrence and malignant transformation.
- To identify areas requiring further research, such as optimal treatment duration and long-term safety.
Main Methods:
- Review of clinical trials and case series on denosumab for GCTB.
- Analysis of recent studies investigating denosumab's impact on local recurrence.
- Examination of in vitro data on denosumab's cellular effects.
- Assessment of reported cases of malignant transformation in GCTB patients treated with denosumab.
Main Results:
- Denosumab demonstrates efficacy in tumor response and surgical down-staging for GCTB.
- Evidence suggests denosumab may increase local recurrence risk, potentially due to altered bone margins and trapped tumor cells.
- In vitro studies indicate a cytostatic rather than cytotoxic effect on neoplastic stromal cells.
- An increasing number of GCTB malignant transformation cases during denosumab treatment have been reported.
Conclusions:
- Denosumab therapy for GCTB requires cautious application due to potential risks.
- Further research is needed to determine optimal treatment duration, long-term safety, and appropriate indications.
- The risk of local recurrence and malignant transformation necessitates careful patient selection and monitoring.
