The current standing on the use of denosumab in giant cell tumour of the bone

Singh, Vivek Ajit; Puri, Ajay

doi:10.1177/2309499020979750

Cited by 13 publications

(17 citation statements)

References 59 publications

(98 reference statements)

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“…In particular, across all patients the most active treatment was the combination of DENO and LENVA both in 2D and 3D ( Figure 3 ). Moreover, LENVA exhibited higher activity both in 2D and 3D compared to bone-target therapy DENO, which represents one of the recommended drugs in the neoadjuvant setting for patients with advanced GCTB who were not candidates for primary curettage [ 40 ]. Taking in consideration DENO, cancer cells’ survival significantly decreased with respect to CTR only in GCTB2, while no significant differences were detected in GCTB3 and DF1 ( Figure 3 B,C,E,F).…”

Section: Resultsmentioning

confidence: 99%

A Rationale for the Activity of Bone Target Therapy and Tyrosine Kinase Inhibitor Combination in Giant Cell Tumor of Bone and Desmoplastic Fibroma: Translational Evidences

et al. 2022

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Giant cell tumor of bone (GCTB) and desmoplastic fibroma (DF) are bone sarcomas with intermediate malignant behavior and unpredictable prognosis. These locally aggressive neoplasms exhibit a predilection for the long bone or mandible of young adults, causing a severe bone resorption. In particular, the tumor stromal cells of these lesions are responsible for the recruiting of multinucleated giant cells which ultimately lead to bone disruption. In this regard, the underlying pathological mechanism of osteoclastogenesis processes in GCTB and DF is still poorly understood. Although current therapeutic strategy involves surgery, radiotherapy and chemotherapy, the benefit of the latter is still debated. Thus, in order to shed light on these poorly investigated diseases, we focused on the molecular biology of GCTB and DF. The expression of bone-vicious-cycle- and neoangiogenesis-related genes was investigated. Moreover, combining patient-derived primary cultures with 2D and 3D culture platforms, we investigated the role of denosumab and levantinib in these diseases. The results showed the upregulation of RANK-L, RANK, OPN, CXCR4, RUNX2 and FLT1 and the downregulation of OPG and CXCL12 genes, underlining their involvement and promising role in these neoplasms. Furthermore, in vitro analyses provided evidence for suggesting the combination of denosumab and lenvatinib as a promising therapeutic strategy in GCTB and DF compared to monoregimen chemotherapy. Furthermore, in vivo zebrafish analyses corroborated the obtained data. Finally, the clinical observation of retrospectively enrolled patients confirmed the usefulness of the reported results. In conclusion, here we report for the first time a molecular and pharmacological investigation of GCTB and DF combining the use of translational and clinical data. Taken together, these results represent a starting point for further analyses aimed at improving GCTB and DF management.

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Section: Resultsmentioning

confidence: 99%

A Rationale for the Activity of Bone Target Therapy and Tyrosine Kinase Inhibitor Combination in Giant Cell Tumor of Bone and Desmoplastic Fibroma: Translational Evidences

et al. 2022

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“…Curettage has a higher recurrence rate [ 15 ], but it preserves joint function. Newer chemotherapy agents like denosumab have become a promising option for reducing the tumor bulk and consolidating the tumor before surgery [ 16 , 17 ]. Its role as an adjuvant when given postoperatively to reduce the chances of recurrence is still controversial.…”

Section: Discussionmentioning

confidence: 99%

Joint preservation surgery in grade 2 and 3 giant cell tumors of bone around the knee

Singh

Rai

Iyer

et al. 2021

SICOT-J

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Objective: To evaluate the clinical and functional outcomes of joint preservation surgery in high-grade giant cell tumors (GCT) around the knee joint. Methods: A retrospective review of 25 patients of high-grade GCT (Campanacci grade 2 and 3) involving proximal tibia or distal femur managed by extended curettage, bone grafting, and stabilization with knee spanning external fixator between 2016 and 2018 was done. The radiographic outcomes, functional outcomes (Musculoskeletal Tumor Society [MSTS] score for lower limb), and complications including donor site morbidity were evaluated. Results: The mean age of the patient population was 24.04 years with an average follow-up period of 30.24 months. Fourteen patients had involvement of distal femur, and 11 involved proximal tibia. There were 16 cases of grade 2 lesions and 9 cases of grade 3 lesions. Twenty-four out of the 25 patients had radiological consolidation of graft, while one patient had graft subsidence. Twenty-two out of 25 patients had full extension and knee flexion more than 100 degrees. The mean MSTS score was 25.2. Three patients had an MSTS score under 20. All three patients had an extension lag with a restricted range of motion. Conclusion: Joint preservation surgery, when done in line with the basic principles of tumor surgery, gives good radiographic and functional outcomes even in grade 2 and 3 giant cell tumors of bone around the knee and should be attempted before replacement surgeries.

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“…Prolonged use may be indicated only in surgically unsalvageable GCTB. 11 In our setup, all the patients underwent definite surgical procedure after a period of 1 month only.…”

Section: Discussionmentioning

confidence: 99%

Post-Denosumab-Treated Giant Cell Tumor of Bone: A Retrospective Histomorphological and Immunohistochemical Study

Kamble

Hui

Rao

et al. 2021

Indian J Med Paediatr Oncol

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Introduction Giant cell tumors of bone (GCTBs) are treated with surgery with or without local adjuvants. Denosumab is a human monoclonal antibody that has recently emerged to be effective in treating unresectable and recurrent GCTBs. Objective In this study, we analyzed the histomorphological changes in GCTB following treatment with denosumab. The expression of histone mutation H3.3G34W by immunohistochemistry (IHC) using mutant specific antibody was also determined. Materials and Methods Of the total 109 GCTBs encountered during the study period, 14 cases with neoadjuvant denosumab therapy were analyzed retrospectively. The post-treatment changes on histopathology were examined on routine hematoxylin and eosin-stained sections. IHC was done using antihistone H3.3G34 antibodies. Statistical analysis was limited to descriptive statistics. No hypothesis testing was performed. Results All these cases except three showed fibrosis with areas of hyalinization, prominent newly formed woven bone along with spindle cells in short fascicles and storiform pattern. There was complete absence and marked reduction in osteoclast-like giant cells in six and five patients, respectively. Only three patients showed a substantial amount of residual osteoclast-like giant cells. IHC with antihistone H3.3G34W antibody showed unequivocal nuclear positivity in the mononuclear cells in nine cases. The mononuclear cells rimming and entrapped within the woven bone were also positive on IHC. The spindle cells in the benign fibrous histiocytoma-like areas and septa of aneurysmal bone cyst-like areas also retained nuclear staining. Conclusion Awareness of post-denosumab-related histopathological changes are necessary to avoid misdiagnosis as fibroosseous lesion and low-grade central osteosarcoma. Expression of mutant-specific H3.3 G34W antibody suggests that the neoplastic stromal cells are largely retained after denosumab therapy. The positive staining of cells both within and those rimming the newly formed woven bone point toward osteoblastic phenotype of the neoplastic stromal cells.

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The current standing on the use of denosumab in giant cell tumour of the bone

Cited by 13 publications

References 59 publications

A Rationale for the Activity of Bone Target Therapy and Tyrosine Kinase Inhibitor Combination in Giant Cell Tumor of Bone and Desmoplastic Fibroma: Translational Evidences

A Rationale for the Activity of Bone Target Therapy and Tyrosine Kinase Inhibitor Combination in Giant Cell Tumor of Bone and Desmoplastic Fibroma: Translational Evidences

Joint preservation surgery in grade 2 and 3 giant cell tumors of bone around the knee

Post-Denosumab-Treated Giant Cell Tumor of Bone: A Retrospective Histomorphological and Immunohistochemical Study

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