The Evaluation and Management of Lung Metastases in Patients with Giant Cell Tumors of Bone in the Denosumab Era.

Giant cell tumor of bone (GCTB) is characterized by uncertain biological behavior due to its local aggressiveness and metastasizing potential. In this study, we conducted a meta-analysis of the contemporary literature to evaluate all management strategies for GCTB metastases. A combination of the terms "lung metastases", "giant cell tumor", "bone", "treatment", and "oncologic outcomes" returned 133 patients meeting our inclusion criteria: 64 males and 69 females, with a median age of 28 years (7-63), at the onset of primary GCTB. Lung metastases typically occur at a mean interval of 26 months (range: 0-143 months) after treatment of the primary site, commonly presenting as multiple and bilateral lesions. Various treatment approaches, including surgery, chemotherapy, radiotherapy, and drug administration, were employed, while 35 patients underwent routine monitoring only. Upon a mean follow-up of about 7 years (range: 1-32 years), 90% of patients were found to be alive, while 10% had died. Death occurred in 25% of patients who had chemotherapy, whereas 96% of those not treated or treated with Denosumab alone were alive at a mean follow-up of 6 years (range: 1-19 years). Given the typically favorable prognosis of lung metastases in patients with GCTB, additional interventions beyond a histological diagnosis confirmation may not be needed. Denosumab, by reducing the progression of the disease, can play a pivotal role in averting or delaying lung failure.

Current Concepts in the Treatment of Giant Cell Tumor of Bone: An Update.

Curettage is recommended for the treatment of Campanacci stages 1-2 giant cell tumor of bone (GCTB) in the extremities, pelvis, sacrum, and spine, without preoperative denosumab treatment. In the distal femur, bone chips and plate fixation are utilized to reduce damage to the subchondral bone and prevent pathological fracture, respectively. For local recurrence, re-curettage may be utilized when feasible. En bloc resection is an option for very aggressive Campanacci stage 3 GCTB in the extremities, pelvis, sacrum, and spine, combined with 1-3 doses of preoperative denosumab treatment. Denosumab monotherapy once every 3 months is currently the standard strategy for inoperable patients and those with metastatic GCTB. However, in case of tumor growth, a possible malignant transformation should be considered. Zoledronic acid appears to be as effective as denosumab; nevertheless, it is a more cost-effective option. Therefore, zoledronic acid may be an alternative treatment option, particularly in developing countries. Surgery is the mainstay treatment for malignant GCTB.

The risk of neurological deterioration while using neoadjuvant denosumab on patients with giant cell tumor of the spine presenting with epidural disease: a meta-analysis of the literature.

BACKGROUND CONTEXT: Giant cell tumor (GCT) of bone is most commonly a benign but locally aggressive primary bone tumor. Spinal GCTs account for 2.7% to 6.5% of all GCTs in bone. En bloc resection, which is the preferred treatment for GCT of the spine, may not always be feasible due to the location, extent of the tumor, and/or the patient's comorbidities. Neoadjuvant denosumab has recently been shown to be effective in downstaging GCT, decreasing the size and extent of GCTs. However, the risk of neurologic deterioration is of major concern for patients with epidural spinal cord compression due to spinal GCT. We experienced this concern when a patient presented to our institution with a midthoracic spinal GCT with progressive epidural disease. The patient was not a good surgical candidate due to severe cardiac disease and uncontrolled diabetes. In considering nonoperative management for this patient, we asked ourselves the following question: What is the risk that this patient will develop neurologic deterioration if we do not urgently operate and opt to treat him with denosumab instead? PURPOSE: The purpose of this study was to assess the literature to (1) determine the risk of neurological deterioration in patients receiving neoadjuvant denosumab for the treatment of spinal GCT and (2) to evaluate the secondary outcomes including radiographic features, surgical/technical complexity, and histological features after treatment. STUDY DESIGN/SETTING: Meta-analysis of the literature. PATIENT SAMPLE: Surgical cases of spinal GCT that (1) presented with type III Campanacci lesions, (2) had epidural disease classified as Bilsky type 1B or above and (3) received neoadjuvant denosumab therapy. OUTCOME MEASURES: The primary outcome measure of interest was neurologic status during denosumab treatment. Secondary outcome measures of interest included radiographic features, surgical/technical complexity, histological features, tumor recurrence, and metastasis. METHODS: Using predetermined inclusion and exclusion criteria, PubMed and Embase electronic databases were searched in August 2022 for articles reporting spinal GCTs treated with neoadjuvant denosumab and surgery. Keywords used were "Spine" AND "Giant Cell Tumor" AND "Denosumab." RESULTS: A total of 428 articles were identified and screened. A total of 22 patients from 12 studies were included for review. 17 patients were female (17/22, 77%), mean age was 32 years (18-62 years) and average follow-up was 21 months. Most GCTs occurred in the thoracic and thoracolumbar spine (11 patients, 50%), followed by 36% in the lumbar spine and 14% in the cervical spine. Almost half of the patients had neurological deficits at presentation (10/22 patients, 45%), and more than 60% had Bilsky 2 or 3 epidural spinal cord compression. None of the patients deteriorated neurologically, irrespective of their neurological status at presentation (p-value=.02, CI -2.58 to -0.18). There were no local recurrences reported. One patient was found to have lung nodules postoperatively. More than 90% of cases had decreased overall tumor size and increased bone formation. Surgical dissection was facilitated in more than 85% of those who had documented surgical procedures. Four patients (18%) underwent initial spinal stabilization followed by neoadjuvant denosumab and then surgical excision of the GCT. Regarding the histologic analyses, denosumab eradicated the giant cells in 95% of cases. However, residual Receptor Activator of Nuclear Factor Kappa B Ligand (RANKL)-positive stromal cells were noted, in 27% (6 cases). CONCLUSIONS: Neoadjuvant denosumab was a safe and effective means of treating spinal GCTs prior to surgery. Neurologic status remained stable or improved in all cases included in our review, irrespective of the presenting neurologic status. The most appropriate dosage and duration of denosumab therapy is yet to be determined. We recommend future well-designed studies to further evaluate the use of neoadjuvant denosumab for patients with spinal GCT.

Human Chorionic Gonadotropin Regulates the Smad Signaling Pathway by Antagonizing TGF-ß in Giant Cell Tumor of Bone.

BACKGROUND: Giant cell tumor of bone (GCTB) is a locally aggressive bone tumour aggravated by stromal cell proliferation and metastasis. OBJECTIVE: We investigated the mechanism of action of human chorionic gonadotropin (HCG) in mediating GCTB proliferation and invasion. METHODS: The expression of HCG was quantified using quantitative real-time PCR. After the primary stromal cells were isolated and identified, the function of HCG in GCTB was estimated using the cell counting kit-8, flow cytometry, scratch experiment, transwell assay, Western blot, and immunofluorescence. Moreover, the mechanism of HCG was assessed through western blotting. RESULTS: HCG expression was decreased in clinical tissue samples from patients with GCTB. We validated that HCG repressed stromal cell proliferation, migration, invasion, autophagy, and epithelial- mesenchymal transition (EMT) and promoted cell apoptosis in GCTB. We also verified that HCG repressed the autophagy and EMT of stromal cells through the Smad signaling axis in GCTB. HCG inhibited the transduction of the Smad signaling pathway by restraining the binding of the TGF-ß II receptor to ligand Activin A. CONCLUSION: HCG restrained the Smad signaling pathway by antagonizing TGF-ß signaling in GCTB. HCG may serve as a useful patent to treat GCTB.

Histological and immunohistochemical analyses of osteoclast maturation in giant cell tumor of bone.

INTRODUCTION: Giant cell tumor of bone (GCTB) is a benign but locally aggressive tumor characterized by the occurrence of multinucleated osteoclast-like giant cells that play a key role in GCTB pathogenesis. However, little is known about the molecular mechanisms underlying osteoclast differentiation in GCTB. Denosumab, a human monoclonal antibody against RANKL, is used for GCTB treatment. Here, we performed morphological and immunohistochemical examinations of pre- and post-denosumab treatment changes by analyzing each stage of osteoclast differentiation. METHODS: We retrieved 15 archival cases of GCTB with tumor samples from both pre- and post-denosumab treatment. We selected three immunohistochemical markers from the expression data from a previous single-cell RNA study: FOS, a progenitor osteoclast marker, and JDP2 and NFATc1, mature osteoclast markers. RESULTS: The mean positivity of the markers decreased after denosumab treatment from 11.1% to 8.9% for FOS, from 10.6% to 7.2% for JDP2, and from 10.0% to 0.2% for NFATc1. Only NFATc1 positivity decreased significantly (P < 0.001) after denosumab treatment. CONCLUSIONS: We identified a new differentiation stage of osteoclast maturation, intermediate cell, by comparing histological findings before and after denosumab treatment. We demonstrated that discrepancies exist between histological and molecular data and highlight the need for establishing an integrated definition of osteoclasts considering morphology and marker expression.

Effect of denosumab in treatment of unresectable spine and sacrum giant cell tumor of bone.

Giant cell tumor of bone (GCTB) is a rare tumor of the bone that is locally invasive. Surgery is the primary treatment that is usually done by intralesional curettage. In pelvis and spine surgery may be associated with high rate of complications, recently, Denosumab has been proposed for the treatment of these tumors in latter anatomical regions. Denosumab may be administered alone or as an adjuvant to surgery. This study aimed to assess the treatment effects of Denosumab in patients with unresectable GCTB. This study was a case series. Patients with unresectable GCTB of vertebra and sacrum were enrolled in this study. Patients received 120 mg of monthly Denosumab and additional doses on days 8th and 15th of treatment. Images of patients before and after treatment were evaluated. Nine patients with a median age of 30 years with spine and sacrum GCTB were included in this study. The median time of treatment with denosumab was 28 months (range: 3-67). Tumor control was seen in all patients. According to Inverse Choi density/size (ICDS), criteria objective response (complete response and partial response) was seen in 8 patients, and one had stable disease. Based on CT scan images, in 4 patients (44.44%), less than 50% of the transverse diameter of the tumor became ossified, and in the other five patients (55.55%), more than 50% of the tumor's transverse diameter became ossified. The median tumor volume before treatment was 829 cm3, and after treatment was 504 cm3 which was significantly reduced (P = 0.005). No complication related to therapy was seen. Tumor response was seen in all patients, and tumor control according to ICDS criteria was evident in all cases. This finding was in line with previous studies. Clinical improvement of signs and symptoms was also seen in all patients. Generally, our study demonstrates a sustained clinical benefit and tumor response with Denosumab, as tumor response ≥ 24 weeks was evident in all cases. No side effects were seen in patients despite long-term treatment with Denosumab.

Diagnosis and monitoring denosumab therapy of giant cell tumors of bone: radiologic-pathologic correlation.

OBJECTIVE: To determine the value of CT and dynamic contrast-enhanced (DCE-)MRI for monitoring denosumab therapy of giant cell tumors of bone (GCTB) by correlating it to histopathology. MATERIALS AND METHODS: Patients with GCTB under denosumab treatment and monitored with CT and (DCE-)MRI (2012-2021) were retrospectively included. Imaging and (semi-)quantitative measurements were used to assess response/relapse. Tissue samples were analyzed using computerized segmentation for vascularization and number of neoplastic and giant cells. Pearson's correlation/Spearman's rank coefficient and Kruskal-Wallis tests were used to assess correlations between histopathology and radiology. RESULTS: Six patients (28 ± 8years; five men) were evaluated. On CT, good responders showed progressive re-ossification (+7.8HU/month) and cortical remodeling (woven bone). MRI showed an SI decrease relative to muscle on T1-weighted (-0.01 A.U./month) and on fat-saturated T2-weighted sequences (-0.03 A.U./month). Time-intensity-curves evolved from a type IV with high first pass, high amplitude, and steep wash-out to a slow type II. An increase in time-to-peak (+100%) and a decrease in Ktrans (-71%) were observed. This is consistent with microscopic examination, showing a decrease of giant cells (-76%), neoplastic cells (-63%), and blood vessels (-28%). There was a strong statistical significant inverse correlation between time-to-peak and microvessel density (ρ = -0.9, p = 0.01). Significantly less neoplastic (p = 0.03) and giant cells (p = 0.04) were found with a time-intensity curve type II, compared to a type IV. Two patients showed relapse after initial good response when stopping denosumab. Inverse imaging and pathological findings were observed. CONCLUSION: CT and (DCE-)MRI show a good correlation with pathology and allow adequate evaluation of response to denosumab and detection of therapy failure.

Narlumosbart: First Approval.

Narlumosbart () is a recombinant, fully human, anti-receptor activator of nuclear factor kappa-Β ligand (RANKL) IgG4 monoclonal antibody being developed by CSPC Pharmaceutical and its wholly owned subsidiary Shanghai Jinmante Biotechnology for the treatment of giant cell tumour of bone (GCTB), bone metastases from solid tumours and osteoporosis. The RANK/RANKL signalling pathway plays a pivotal role in osteoclastogenesis and in the pathogenesis of GCTB. Narlumosbart specifically binds to RANKL and blocks the interaction of RANKL with RANK, thus inhibiting osteoclastogenesis and bone resorption by osteoclasts. In September 2023, narlumosbart received conditional first approval in China for the treatment of adults with GCTB that is unresectable or when surgical resection would result in severe functional disability. Clinical studies of narlumosbart for bone metastases, postmenopausal osteoporosis and glucocorticoid-induced osteoporosis are underway in China. This article summarizes the milestones in the development of narlumosbart leading to this first approval for the treatment of adults with GCTB.

Denosumab for an inoperable giant cell tumour of the ischial bone.

Giant cell tumour of bone is a benign, locally aggressive osteolytic tumour that typically affects skeletally mature young individuals. It predominantly emerges within the metaphysis, extending towards the epiphysis of long bones, while occurrences in flat bones are exceptionally rare. We present a case of a woman in her late 20s who presented with a large right ischial mass. A biopsy confirmed the mass as a giant cell tumour. The tumour extended to the acetabulum, and due to the potential risk of significant bleeding and contamination during en bloc excision, a prudent approach involved initiating denosumab therapy, a monoclonal antibody targeting receptor activator of nuclear factor-κB ligand therapy, before proceeding with radical surgery. Denosumab therapy successfully rendered a previously inoperable tumour favourable for surgical intervention. We went on to perform a type 2 and 3 internal hemipelvectomy, followed by a reconstruction with a hip endoprosthesis replacement.

Conversion in a Resectable Tumor after Denosumab Neoadjuvant in a Large Dorsal Giant Cells Tumor: A Case Report and a Literature Review.

Giant cell tumors of bone are a rare entity, usually occurring in young patients and characteristically arising in the long bones. The spinal location is rare and usually presents with pain and/or neurological symptoms. The treatment of choice is surgery. Treatment with Denosumab, a bisphosphonate inhibitor of RANK-L, which is highly expressed in these tumors, has shown extensive activity in unresectable patients or those undergoing incomplete surgery. Preoperative treatment with this drug is gaining increasing interest, as its high potency in tumor reduction in this subtype of neoplasm has allowed resectability in selected patients. We present the case of a young patient with a large spinal tumor who, after neoadjuvant Denosumab, underwent complete en bloc surgery with clean margins and a great pathological response.

Denosumab in Giant Cell Rich Tumors of Bone: An Open-Label Multicenter Phase II Study.

BACKGROUND: Since giant cell tumors of bone (GCTB) and other giant cell rich tumors of bone (GCRTB) share the histological presence of osteoclastic giant cells and expression of RANK/RANKL, we hypothesized that GCRTB will respond similarly to denosumab as GCTB. The primary objective of this study was to determine the efficacy of denosumab in patients with GCRTB that have recurred or require morbid surgery. METHODS: In this open-label, multicenter, phase II trial, patients with GCRTB were included (June 2018-March 2020). Recruitment was stopped because of low accrual. Patients received denosumab (120 mg) subcutaneously (SC) on day 1 of every 4-week cycle with a loading dose of 120 mg SC on days 8 and 15. RESULTS: Three patients were enrolled. One withdrew consent before start of study. The remaining patients had central giant cell granuloma of the jawbone (CGCG). Median treatment duration was 15 cycles (range 12-18). In both subjects, improvement in ossification of lesions was seen. Median follow-up was 28.5 months (range 20-37). One patient developed a recurrence for which surgery was performed. CONCLUSION: Due to critical emerging real-world data of denosumab in GCRTBs, the study was prematurely stopped and not supportive of use of denosumab for this indication. (ClinicalTrials.gov Identifier: NCT03605199).

Histopathological response to denosumab in giant cell tumours of bone - A review of 11 cases.

Background: Giant cell tumor (GCT) of the bone is a locally aggressive primary bone tumor, that can rarely metastasize. Arising mostly in epiphysis of the long bones in young adults, the tumor is composed of mononuclear cells that are admixed with osteoclastic giant cells(OLGCs), which express RANK ligand and RANK respectively. Denosumab a monoclonal antibody against RANK ligand has been shown to reduce the tumor by causing bone lysis by inhibiting RANKL. Histological changes in 11 patients of GCT who were treated with denosumab are presented here. Materials and Methods: Clinical records and slides of 11 patients of GCT who had been administered neoadjuvant denosumab were included in the study. Evaluation of pre and post therapy GCT specimens was performed by two pathologists (RK and VM). There were 4 males and 7 females. Their mean age was 30 years. All the patients received 120 mg denosumab subcutaneously every week with additional 120 mg on days 8 and 15 of therapy. The histological slides were reviewed and following points noted: 1) degree of ossification,2) fibrosis,3) loss of osteoclastic giant cells,4) proliferation of mononuclear cells,5) atypia,6) Permeation of osteoid by malignant cells. Results: Out of 11 cases, 2 cases did not show any significant histological improvement. 7 cases showed reduction in giant cells, increased fibrosis, enhanced mononuclear cell proliferation and ossification consistent with a pathological response. Atypia and osteoid permeation were noted in 2 cases which showed transformation to osteosarcoma. Conclusion: Denosumab treated giant cell tumor show dramatic histological changes. The post therapy lesions may bear no resemblance to pretherapy lesion. There may be complete resolution or may be confused with benign or malignant lesions Rarely they may show sarcomatous transformation. It is imperative that the pathologist is aware of these changes to prevent diagnostic pitfalls as it poses therapeutic and prognostic implications.

Effect evaluation of denosumab combined with curettage and bone cement reconstruction in the treatment of recurrent giant cell tumor of bone around the knee joint.

OBJECTIVE: Giant cell tumor of bone (GCTB) is a common primary bone tumor with latent malignant tendency. GCTB is prone to occur around the knee joint, and surgery is the major treatment method. There are relatively few reports on denosumab in the treatment of recurrent GCTB around the knee joint and postoperative function evaluation of patients. This research aimed to explore the appropriate surgical options for the treatment of recurrent GCTB around the knee joint. PATIENTS AND METHODS: 19 patients with recurrent GCTB around the knee joint, who were admitted to Hospital for 3 months following denosumab treatment from January 2016 to December 2019, were included as the research subjects. The prognosis was compared between patients treated with curettage combined with polymethylmethacrylate (PMMA) and those with extensive-resection replacement of tumor prosthesis (RTP). A deep learning model of Inception-v3 combined with a Faster region-based convolutional neural network (Faster-RCNN) was constructed to classify and identify X-ray images of patients. The Musculoskeletal Tumor Society (MSTS) score, short form-36 (SF-36) score, recurrence, and the rate of complications were also analyzed during the follow-up period. RESULTS: The results showed that the Inception-v3 model trained on the low-rank sparse loss function was obviously the best for X-ray image classification, and the classification and identification effect of the Faster-RCNN model was significantly better than that of the convolutional neural network (CNN), U-Net, and Fast region-based convolutional neural network (Fast-RCNN) models. During the follow-up period, the MSTS score in the PMMA group was significantly higher than that in the RTP group (p<0.05), while there was no significant difference in the SF-36 score, recurrence, and the rate of complications (p>0.05). CONCLUSIONS: The deep learning model could improve the classification and identification of the lesion location in the X-ray images of GCTB patients. Denosumab was an effective adjuvant for recurrent GCTB, and widely extensive-resection RTP could reduce the risk of local recurrence after denosumab treatment for recurrent GCTB.

The efficacy and safety of short-course neoadjuvant denosumab for en bloc spondylectomy in spinal giant cell tumor of bone: a preliminary report.

PURPOSE: This study aimed to investigate whether short course of neoadjuvant denosumab treatment for spinal GCTB could (1) Induce radiological and histological response? (2) Facilitate en bloc resection? (3) Achieve satisfactory oncological and functional outcomes? METHODS: The clinical information of ten consecutive patients between 2018 and 2022 with spinal GCTB treated with short course of neoadjuvant denosumab (≤ 5 doses) and en bloc spondylectomy was retrospectively reviewed. The radiological and histological response, operative data, oncological and functional outcomes were analyzed. RESULTS: The mean doses of neoadjuvant denosumab were 4.2 (range 3-5 doses). After neoadjuvant denosumab, there were 9 cases showing new ossification and 5 cases with reappearance of cortical integrity. The values of Hounsfield units (HU) of the soft tissue component were increased by > 50% in 7 cases. The signal intensity (SI) ratios of tumor/muscle in T2WI of plain MRI were decreased by > 10% in 60% of the cases. Shrinkage of soft tissue mass by > 10% was observed in 4 cases. The mean duration of operation was 575 ± 174 min, and the mean estimated blood loss (EBL) was 2790 ± 1934 ml. No obvious adhesion to dura mater or major vessels was encounter intraoperatively. There is no tumor collapse or breakage during surgery. Multinucleated giant cells were decreased in 6 cases (60%) with the remaining 4 cases showing absence of multinucleated giant cells. Mononuclear stromal cells existed in most of the cases (8 cases, 80%). New bone formation was noticed in 8 cases (80%). No patient had a worsening of neurologic function after surgery. No tumor recurrence was noticed within the mean follow-up of 24 ± 20 months. CONCLUSION: Short-term neoadjuvant denosumab could yield radiological and histological responses and might facilitate en bloc spondylectomy by hardening the tumor and causing less adhesion to segmental vessels, major vessels and nerve roots, which was beneficial to achieve the optimal oncological and functional outcomes.

Preoperative denosumab treatment in patients with giant cell bone tumors in limbs: A retrospective study using propensity score matching.

BACKGROUND AND OBJECTIVES: Denosumab is recommended for advanced giant cell tumor of bone (GCTB) that is unresectable or resectable with unacceptable morbidity. But the effect of preoperative denosumab treatment on the local control GCTB remains controversial. METHODS: We conducted a study of 49 patients with GCTB in the limbs treated with denosumab before surgery and 125 patients without in our hospital from 2010 to 2017. Propensity-score matching (PSM) at a 1:1 ratio between the denosumab and control groups was performed to minimize possible selection bias, and compared the recurrence rate, limb function, and surgical degradation between the two groups. RESULTS: The 3-year recurrence rates in the denosumab group and the control group were 20.4% and 22.9% after PSM, respectively (p = 0.702). In the denosumab group, 75.5% (n = 37/49) of patients experienced surgical downgrading. Limb joint preservation rates were 92.1% (35) for 38 patients treated with denosumab and 60.2% (71) for 118 control subjects. (p ≺ 0.001). Postoperative MSTS were higher in patients in the denosumab group than in the control group (24.1 vs. 22.6, p = 0.034). CONCLUSIONS: Preoperative denosumab treatment did not result in an increased risk of local recurrence of GCTB. Patients with advanced GCTB may benefit from preoperative denosumab treatment for surgical downgrading and the preservation of the joint.

Association between preoperative denosumab and the risk of local recurrence in patients with giant cell tumor of bone: A meta-analysis and systematic review.

Objectives: This meta-analysis aimed at determining the association between preoperative denosumab and the risk of local recurrence in patients with giant cell tumors of the bone. Methods and Materials: Web of Science, EMBASE, Cochrane Library, and PubMed were comprehensively searched on April 20th, 2022. Data from the included articles were analyzed using meta-analysis. The bias of all included studies was evaluated according to ROBINS-I. Also, subgroup and sensitivity analyses were performed. Results: Eight studies with 1270 cases (195 in the denosumab group and 1075 in the control group) were eventually included. Patients receiving denosumab before curettage had a higher risk of local recurrence than those who underwent curettage alone (odds ratio: 2.29, 95% confidence intervals: 1.44-3.64, P = 0.0005). The denosumab group showed a significantly higher risk of local recurrence in most subgroup analyses, except for those with preoperative denosumab duration ≤six months/doses (P = 0.66) and sample size ranging from 100 to 180 (P = 0.69). Conclusion: Denosumab before curettage may increase the risk of local recurrence in patients with giant cell tumor of the bone. Preoperative denosumab should be used with caution after weighing an increased risk of local recurrence against the clinical benefits and a duration time of less than six months before surgery is recommended.

[Giant cell tumour of bone in the rib cage treated with denosumab. A case report]. / Tumor de células gigantes óseo en arco costal, tratado con denosumab. Reporte de un caso.

Giant cell tumour of bone (GCTOB) accounts for 4-5% of all primary bone tumours and occurs most frequently in females between 20 and 45 years old. It is found in the epiphyses of the long bones, vertebral bodies and flat bones. We report the case of a 31-year-old woman who presented with a one month history of thoracic pain. On examination, a mass was found in the right breast with signs of an ipsilateral pleural effusion. A thoracic CAT scan revealed an infiltrating mass which was subsequently biopsied and a GCTOB was diagnosed. Due to the localization and the morphology, a wide range of differential diagnoses were considered. Genetic studies detected a mutation of the gene H3F3A, supporting the original diagnosis. The patient underwent treatment with denosumab followed by surgical resection of the mass. The histopathology of the tumour revealed various histological changes which were a source of diagnostic pitfalls.

Denosumab for giant cell tumors of bone from 2010 to 2022: a bibliometric analysis.

Giant cell tumors of the bone (GCTB) are considered moderately malignant bone tumors. Denosumab, as a neoadjuvant therapy, provides new possibilities for treating GCTB. However, even after multiple studies and long-term clinical trials, there are limitations in the treatment process. Research data and Medical Subject Headings terms related to denosumab and GCTB were collected from January 2010 to October 2022 using the Web of Science and MeSH ( https://meshb.nlm.nih.gov ) browsers. These data were imported into CiteSpace and VOSviewer softwares for bibliometric analysis. Overall, 445 publications on denosumab and GCTB were identified. Over the last 12 years, the growth rate of the total number of publications has remained relatively stable. The USA published the highest number of articles (83) and had the highest centrality (0.42). Amgen Inc. and Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) First Ortoped Rizzoli were identified as the most influential institutions. Many authors have made outstanding contributions to this field. Lancet Oncology had the highest journal impact factor (54.433). Local recurrence and drug dosage are current research hotspots, and future development trends will mainly focus on prognostic markers of GCTB and the development of new therapies. Further research is required to analyze denosumab's safety and efficacy and understand its local recurrence of GCTB, to identify the optimal dose. Future progress in this field will likely focus on exploring new diagnostic and recurrence markers to monitor disease progression and examine new therapeutic targets and treatment strategies.

Denosumab salvage therapy in an 11-year-old boy with locally recurrent unresectable giant cell tumor of the lumbar spine after surgery.

Giant cell tumors (GCTs) of the bone are locally aggressive primary bone tumors with a benign character. Spinal involvement is rare which accounts for approximately 5% of all primary bone tumors and it is quite rare in the lumbar spine. An 11-year-old boy patient presented with pain of low back and bilateral low extremities. Lumbar CT and MRI revealed a lytic lesion of the L4 vertebra corpus. The patient earned remarkable and timely recovery with 2 surgical interventions and the use of denosumab. Surgical resection for GCTs is still preferable as the initial treatment, denosumab should be utilized after tumor resection whether based on the purpose of prevention or treatment of tumor recurrence.