Giant Cell Tumor of Bone: An Update

Mallick, Atrayee Basu; Chawla, Sant P.

doi:10.1007/s11912-021-01047-5

Cited by 48 publications

(59 citation statements)

References 40 publications

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“…There was a complete depletion of multinucleated giant cells and mononuclear stromal cells. Treatment with denosumab led to the disappearance of all giant osteoclast-like cells in the tumor tissue [ 14 , 17 , 54 ], implying that sunitinib contributed to the suppression of stromal tumor cells. Interestingly, such a complete response has been achieved with sunitinib at the recommended dose for the treatment of malignancies according to the approved product label.…”

Section: Discussionmentioning

confidence: 99%

New Target for Precision Medicine Treatment of Giant-Cell Tumor of Bone: Sunitinib Is Effective in the Treatment of Neoplastic Stromal Cells with Activated PDGFRβ Signaling

Mahdal

Neradil

Múdrý

et al. 2021

Cancers

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Giant-cell tumor of bone (GCTB) is an intermediate type of primary bone tumor characterized by locally aggressive growth with metastatic potential. The aim of this study was to identify new druggable targets among the cell signaling molecules involved in GCTB tumorigenesis. Profiles of activated signaling proteins in fresh-frozen tumor samples and tumor-derived cell lines were determined using phosphoprotein arrays. Analysis of the obtained data revealed epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor beta (PDGFRβ) as potential targets, but only the PDGFR inhibitor sunitinib caused a considerable decrease in stromal cell viability in vitro. Furthermore, in the case of a 17-year-old patient suffering from GCTB, we showed that the addition of sunitinib to the standard treatment of GCTB with the monoclonal antibody denosumab resulted in the complete depletion of multinucleated giant cells and mononuclear stromal cells in the tumor tissue. To summarize, the obtained data showed that a specific receptor tyrosine kinase (RTK) signaling pattern is activated in GCTB cells and plays an important role in the regulation of cell proliferation. Thus, activated RTKs and their downstream signaling pathways represent useful targets for precision treatment with low-molecular-weight inhibitors or with other types of modern biological therapy.

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Section: Discussionmentioning

confidence: 99%

New Target for Precision Medicine Treatment of Giant-Cell Tumor of Bone: Sunitinib Is Effective in the Treatment of Neoplastic Stromal Cells with Activated PDGFRβ Signaling

Mahdal

Neradil

Múdrý

et al. 2021

Cancers

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“…Extended curettage and segmental tumor resection are often used in clinical practice ( 10 , 11 ). Still, even in the most commonly seen cases of GCTB of the knee joint, when combined with pathological fractures or Campanacci grade III, the choice of the two surgical methods remains controversial ( 20 , 21 ). There are even fewer systematic studies for GCTB of the proximal femur to clarify the reference criteria for surgical selection.…”

Section: Discussionmentioning

confidence: 99%

Comparative Analysis of Two Surgical Treatment Options for Giant Cell Tumor of the Proximal Femur: Extended Curettage and Segmental Resection

Yuan

Liu

et al. 2021

Front. Oncol.

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AimAs a locally destructive intermediate bone tumor with low incidence, high recurrence rate, and difficulty in reconstruction, giant cell tumor of bone (GCTB) in the proximal femur has no unified surgical treatment standard. This study aimed to compare the differences in local recurrence, reconstruction durability, and postoperative function after treatment with either extended curettage (EC) or segmental resection (SR) for GCTB in the proximal femur so as to provide constructive suggestions for the rational selection of EC or SR operation scheme.Patients and Methods29 patients (15 men and 14 women) were included in this retrospective study, with a mean age of 32.1 years. According to the division method of proximal femur of International Society Of Limb Salvage (ISOLS), there was 1 case in the H1 area, 17 cases in the H2 area, 10 cases in the H1+H2 area, and 1 case in the H1+H2+H3 area. Among them were 11 cases of Campanacci grade II GCTB, 18 cases of Campanacci grade III GCTB, and 7 cases with pathological fractures. All patients underwent either EC or SR surgery. The Musculoskeletal Tumor Society (MSTS) score was used for patient evaluation. The operation effectiveness was analyzed according to the Mankin evaluation standard. Regular follow-up was performed to evaluate the recurrence rate, limb function, and long-term complications of the two surgical methods.ResultsAll patients were followed up for a mean of 60.4 months. Local recurrence occurred in one of 19 patients treated with EC (5.3%) and one of 10 patients treated with SR (10%). The MSTS score of lower limb function in patients in the EC group was better compared to patients in the SR group (P = 0.002). Complications occurred in 2 cases (10.5%) and 5 cases (50%) in the EC group (osteoarthritis, osteonecrosis) and SR group (joint stiffness, infection, prosthesis loosening), respectively, with significant differences between the two groups (P = 0.03). The operation effectiveness was analyzed according to the Mankin evaluation standard. The EC group showed an optimal rate of 94.7% (18/19) as opposed to 80% (8/10) in the SR group.ConclusionsFor GCTB in the proximal femur, when the tumor does not extensively involves the surrounding soft tissues, the articular surface was not damaged, and there is no pathological fracture with apparent displacement, EC surgery should be fully considered.

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“…9 Alternatively, en-bloc resection reduces recurrence risks but is associated with significant morbidity. 7 Systemic and locoregional therapies for primary disease include denosumab, bisphosphonates, interferon, radiotherapy and serial arterial embolization. 4,8 Denosumab is preferred for unresectable primary GCTB or utilized neoadjuvantly to facilitate less morbid resections.…”

Section: Introductionmentioning

confidence: 99%

“…Despite extending the curettage margin with local adjuvant therapy, recurrence rates still remain high at around 30% 9 . Alternatively, en‐bloc resection reduces recurrence risks but is associated with significant morbidity 7 . Systemic and locoregional therapies for primary disease include denosumab, bisphosphonates, interferon, radiotherapy and serial arterial embolization 4,8 .…”

Section: Introductionmentioning

confidence: 99%

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Metastatic giant cell tumour of bone: a narrative review of management options and approaches

Choong

2022

ANZ Journal of Surgery

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Giant cell tumour of bone (GCTB) is a locally aggressive bone neoplasm with a rare tendency to metastasise, most commonly to the lungs. The management of metastatic GCTB (metGCTB) is controversial due to its unpredictable behaviour. Asymptomatic patients should be monitored radiologically and undergo treatment only when disease progression occurs. Surgery is recommended for resectable metGCTB. Denosumab, a monoclonal antibody which inhibits receptor activator of nuclear factor‐κB ligand, is recommended for unresectable metGCTB with evidence from phase II trials demonstrating its safety and efficacy. Relapse after denosumab withdrawal may occur and prolonged treatment may be associated with serious adverse events, thus further research is warranted to inform a maintenance regimen with reduced dosing and frequency. Combined denosumab and bisphosphonate therapy has the potential to achieve sustained disease control or remission in unresectable metGCTB without requiring long‐term treatment and should be evaluated in prospective trials. Various novel agents have demonstrated in vitro and anecdotal efficacy and warrant further evaluation.

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Giant Cell Tumor of Bone: An Update

Cited by 48 publications

References 40 publications

New Target for Precision Medicine Treatment of Giant-Cell Tumor of Bone: Sunitinib Is Effective in the Treatment of Neoplastic Stromal Cells with Activated PDGFRβ Signaling

New Target for Precision Medicine Treatment of Giant-Cell Tumor of Bone: Sunitinib Is Effective in the Treatment of Neoplastic Stromal Cells with Activated PDGFRβ Signaling

Comparative Analysis of Two Surgical Treatment Options for Giant Cell Tumor of the Proximal Femur: Extended Curettage and Segmental Resection

Metastatic giant cell tumour of bone: a narrative review of management options and approaches

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