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Current Concepts in the Treatment of Giant Cell Tumors of Bone.

ABSTRACT: The 2020 World Health Organization classification defined giant cell tumors of bone (GCTBs) as intermediate malignant tumors. Since the mutated H3F3A was found to be a specific marker for GCTB, it has become very useful in diagnosing GCTB. Curettage is the most common treatment for GCTBs. Preoperative administration of denosumab makes curettage difficult and increases the risk of local recurrence. Curettage is recommended to achieve good functional outcomes, even for local recurrence. For pathological fractures, joints should be preserved as much as possible and curettage should be attempted. Preoperative administration of denosumab for pelvic and spinal GCTBs reduces extraosseous lesions, hardens the tumor, and facilitates en bloc resection. Nerve-sparing surgery after embolization is a possible treatment for sacral GCTBS. Denosumab therapy with or without embolization is indicated for inoperable pelvic, spinal, and sacral GCTBs. It is recommended to first observe lung metastases, then administer denosumab for growing lesions. Radiotherapy is associated with a risk of malignant transformation and should be limited to cases where surgery is impossible and denosumab, zoledronic acid, or embolization is not available. Local recurrence after 2 years or more should be indicative of malignant transformation. This review summarizes the treatment approaches for non-malignant and malignant GCTBs.

SUBMITTER: Tsukamoto S

PROVIDER: S-EPMC8344974 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Giant cell tumors of bone (GCTB) are locally aggressive osteolytic bone tumors. Recently, some clinical trials have shown that denosumab is a novel and effective therapeutic option for aggressive and recurrent GCTB. This study was performed to investigate the molecular mechanism underlying the therapeutic effect of denosumab. Comparative proteomic analyses were performed using GCTB samples which were taken before and after denosumab treatment. Each expression profile was analyzed using the software program to further understand the affected biological network. One of identified proteins was further evaluated by gelatin zymography and an immunohistochemical analysis. We identified 13 consistently upregulated proteins and 19 consistently downregulated proteins in the pre- and post-denosumab samples. Using these profiles, the software program identified molecular interactions between the differentially expressed proteins that were indirectly involved in the RANK/RANKL pathway and in several non-canonical subpathways including the Matrix metalloproteinase pathway. The data analysis also suggested that the identified proteins play a critical functional role in the osteolytic process of GCTB. Among the most downregulated proteins, the activity of MMP-9 was significantly decreased in the denosumab-treated samples, although the residual stromal cells were found to express MMP-9 by an immunohistochemical analysis. The expression level of MMP-9 in the primary GCTB samples was not correlated with any clinicopathological factors, including patient outcomes. Although the replacement of tumors by fibro-osseous tissue or the diminishment of osteoclast-like giant cells have been shown as therapeutic effects of denosumab, the residual tumor after denosumab treatment, which is composed of only stromal cells, might be capable of causing bone destruction; thus the therapeutic application of denosumab would be still necessary for these lesions. We believe that the protein expression patterns and the results of the network analysis will provide a better understanding of the effects of denosumab administration in patients with GCTB.

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Current Concepts in the Treatment of Giant Cell Tumors of Bone.

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