Explore the vast range of titles available.

Background Giant cell tumor of bone (GCTB) is a rare osteoclastogenic stromal tumor. GCTB can rarely undergo malignant transformation. This post hoc analysis evaluated and classified malignancies in patients with GCTB who received denosumab. Methods This analysis was conducted on patients with pathologically confirmed GCTB and measurable active disease treated with denosumab 120 mg subcutaneously once every 4 weeks, with loading doses on study days 8 and 15, as part of a phase 2, open-label, multicenter study. We identified potential cases of malignancy related to GCTB through an independent multidisciplinary review or medical history, associated imaging or histopathologic reports, and disease course. The findings were summarized and no statistical analysis was performed. Results Twenty of five hundred twenty-six patients (3.8%) who received at least one dose of denosumab were misdiagnosed with GCTB that was later discovered to be malignancies: five primary malignant GCTB, five secondary malignant GCTB, four sarcomatous transformations, and six patients with other malignancies (giant cell-rich osteosarcoma, undifferentiated pleomorphic sarcoma, spindle cell sarcoma, osteogenic sarcoma, phosphaturic mesenchymal tumor of mixed connective tissue type, and fibrosarcoma/malignant fibrous histiocytoma). Many malignancies were present before denosumab was initiated (8 definitive cases, 7 likely cases), excluding potential involvement of denosumab in these cases. Signs associated with potential misdiagnoses of GCTB included poor mineralization with denosumab treatment, rapid relapse in pain, or a failure of the typical dramatic improvement in pain normally observed with denosumab. Conclusions Although rare, GCTB can undergo malignant transformation, and rates in this study were consistent with previous reports. Signs of poor mineralization or lack of response to denosumab treatment may warrant close monitoring. Trial registration clinicaltrials.gov , ( NCT00680992 ). Registered May 20, 2008.

Bone sarcomas are tumours belonging to the family of mesenchymal tumours and constitute a highly heterogeneous tumour group. The three main bone sarcomas are osteosarcoma, Ewing sarcoma and chondrosarcoma each subdivided in diverse histological entities. They are clinically characterised by a relatively high morbidity and mortality, especially in children and adolescents. Although these tumours are histologically, molecularly and genetically heterogeneous, they share a common involvement of the local microenvironment in their pathogenesis. This review gives a brief overview of their specificities and summarises the main therapeutic advances in the field of bone sarcoma.

Background: Primary and recurrent giant cell tumor of bone is typically benign; however, rarely giant cell tumor of bone can undergo malignant transformation. Malignancy in giant cell tumor of bone may be primary (adjacent to benign giant cell tumor of bone at first diagnosis) or secondary (at the site of previously treated giant cell tumor of bone). Malignant giant cell tumor of bone has a poor prognosis; it is important to distinguish malignant from benign lesions to facilitate appropriate management. The true incidence of malignant giant cell tumor of bone is not known, probably owing to inaccurate diagnosis and inconsistent nomenclature. We have analyzed current data to provide a robust estimate of the incidence of malignancy in giant cell tumor of bone. Methods: A literature search was performed to source published reports of primary and secondary cases of malignant giant cell tumor of bone. Studies that reported a denominator were used to estimate the incidence of malignancy. Results: We identified 4 large series of patients with malignant giant cell tumor of bone that provided data on 2315 patients with giant cell tumor of bone. Across these studies, the cumulative incidence of malignancy was 4.0%; the cumulative incidence of primary malignancy was 1.6% compared with 2.4% for secondary malignancy. Our analyses confirmed that most malignant giant cell tumor of bone is secondary and occurs following radiation. In addition, data from 8 small series showed that 4.8% of patients with giant cell tumor of bone who received radiation therapy developed secondary malignancy. Conclusions: Malignant giant cell tumor of bone is rare, and its identification is hindered by a lack of clear diagnostic criteria. For optimal care of patients with giant cell tumor of bone, we recommend: comprehensive histologic sampling to ensure accurate diagnoses; watchful follow-up, particularly for patients treated with radiation; and timely treatment of local recurrence.

Background Surgical resection with curative intent for giant cell tumor of bone (GCTB) may be associated with severe morbidity. This interim analysis evaluated reduction in surgical invasiveness after denosumab treatment in patients with resectable GCTB. Methods Patients with primary or recurrent GCTB, for whom the initially planned surgery was associated with functional compromise or morbidity, received denosumab 120 mg subcutaneously every 4 weeks (additional doses on days 8 and 15 of the first cycle). Planned and actual GCTB-related surgical procedures before and after denosumab treatment were reported. Patients were followed for surgical outcome, adverse events, and recurrence following resection. Results Overall, 222 patients were evaluable for surgical downstaging (54 % were women; median age 34 years). Lesions (67 % primary and 33 % recurrent) were located in the axial (15 %) and appendicular skeleton (85 %). At the data cutoff date, most patients had not yet undergone surgery ( n  = 106; 48 %) or had a less morbid procedure ( n  = 84; 38 %) than originally planned. Median (interquartile range) time on denosumab was 19.5 (12.4–28.6) months for the 106 patients who had not undergone surgery and were continuing on monthly denosumab. Native joint preservation was 96 % ( n  = 24/25) for patients with planned joint/prosthesis replacement and 86 % ( n  = 30/35) for patients with planned joint resection/fusion. Of the 116 patients who had surgery (median postsurgical follow-up 13.0 [8.5–17.9] months), local recurrence occurred in 17 (15 %) patients. Conclusion For patients with resectable GCTB, neoadjuvant denosumab therapy resulted in beneficial surgical downstaging, including either no surgery or a less morbid surgical procedure.

Background Giant cell tumor of bone (GCTB) is a locally aggressive neoplasm with variable biological behavior. Programmed death-ligand 1 (PD-L1) has been implicated in tumor progression across multiple malignancies, but its relationship to growth kinetics in GCTB remains unclear. This study investigated whether PD-L1 mRNA expression correlates with tumor growth rate in extremity GCTB. Methods This single-institution retrospective cohort study included 36 patients with GCTB treated surgically between January 2020 and December 2024. Of these, 18 provided consent for research use of tissue; four were excluded due to lack of serial MRI data, yielding a final cohort of 14 patients. PD-L1 mRNA levels were quantified using real-time PCR. Tumor volumes were segmented from MRI using 3D Slicer, and growth rate (cc/month) was calculated. Patients were stratified into high- and low-PD-L1 groups using the cohort median fold change (2.62) as an exploratory cutoff. Group comparisons used Mann–Whitney U and Fisher’s exact tests, and Spearman’s rank correlation analysis was performed to assess the relationship between continuous PD-L1 expression and tumor growth rate. Exploratory linear regressions were performed adjusting for age, sex, tumor site, and preoperative denosumab use. Results Median age was 32 years; 57% were male. Tumors with high PD-L1 expression showed faster growth than those with low expression (5.0 [1.3–7.1] vs. 0.8 [0.2–2.1] cc/month; p  = 0.038). This relationship was further supported by a significant positive correlation between PD-L1 mRNA levels and tumor growth rate ( ρ  = 0.6, p  = 0.026). The association remained significant in exploratory multivariable and robust regression analyses adjusting for covariates. Conclusions Higher PD-L1 mRNA expression correlated with accelerated tumor growth in extremity GCTB. These exploratory findings suggest PD-L1 may serve as a potential biomarker of tumor aggressiveness, warranting validation in larger cohorts.

Background A giant cell tumor of bone is a primary benign but locally aggressive neoplasm. Malignant transformation in a histologically typical giant cell tumor of bone, without radiotherapy exposure, is an uncommon event, occurring in less than 1% of giant cell tumors of bone. Although surgery is the standard initial treatment, denosumab, a monoclonal antibody drug that inhibits receptor activator of nuclear factor-κB ligand (RANKL), has shown considerable activity regarding disease and control of symptoms in patients with recurrence, unresectable, and metastatic giant cell tumors of bone. Case Description We report the case of a 20-year-old woman with a recurrent benign, giant cell tumor of bone, who had a bone sarcoma develop while receiving denosumab treatment. Literature Review To our knowledge, there have been no reports of infection or malignancy with low-dose denosumab administration for osteoporosis. However, while there are relatively few reported side effects, the safety of denosumab and adverse events seen with higher doses, as used in treatment of giant cell tumors of bone are not well defined. Clinical Relevance Denosumab has become a valuable adjunct for treatment of recurrent or unresectable giant cell tumor of bone. It is not clear if our patient’s malignant transformation of a giant cell tumor of bone while receiving denosumab treatment was caused by denosumab, but it is important to be aware of the possibility if more cases occur. Future studies should focus on the safety of high-dose denosumab administration in patients with a benign unresectable giant cell tumor of bone.

Purpose of ReviewTo highlight the new developments in the management of advanced giant cell tumor of bone, a rare locally aggressive benign tumor, which was traditionally managed with surgery alone by either curettage and local adjuvant therapy, wide resection, or marginal excision. Here, we review the current role of systemic therapy for management of locally advanced or metastatic giant cell tumor of bone (GCTB).Recent FindingsThe elucidation of the pathophysiology of giant cell tumor of bone, especially with regards to the role of nuclear factor kappa B ligand (RANKL), has led to the Food and Drug Administration (FDA) approval of denosumab in the management of locally advanced or metastatic GCTB.SummaryFor advanced giant cell tumor where surgical resection alone can cause severe morbidity, the paradigm has shifted from local treatment alone to multidisciplinary management with the consideration of use of denosumab.

Background Juxta-articular giant cell tumors in the talus are very rare and pose a special problem for reconstruction after aggressive tumor curettage. Currently, vascularized iliac bone graft (VIBG) has proven to improve the outcome of partial talus defect, however, technical difficulty occurs when both the three-dimensional fitting for a large cavity and structural support to the articular surface in the talus are needed. Prior publications have demonstrated that the three-dimensional printing technology can improve surgical efficiency on the vascularized bone graft for extremity and mandibular reconstructions in complex clinical scenarios. Case presentation We report the case of a Campanacci grade III giant cell tumor of the right talus, involving the subchondral bone close to four articular surfaces and extending into the medial soft tissue. The tumor was successfully managed with a downgrading strategy that combined microwave ablation and curettage, followed by reconstruction via a VIBG guided by a three-dimensional printed model. Computed tomography scans confirmed bone union at two months postoperatively. Two years after surgery, collapse of the articular surface or evidence of recurrence or osteonecrosis was not observed. The patient achieved a normal gait with 15 degrees of ankle dorsiflexion and 45 degrees of plantar flexion under weightbearing conditions. Conclusion The reconstruction of the large residual cavity in the talus with a VIBG after microwave ablation and aggressive tumor removal of giant cell tumor under the guidance of a three-dimensional printed model enabled the preservation of the ankle function.

Giant cell tumor of bone (GCTB) presents considerable complexity in tumor microenvironment (TME) because of its intricate intercellular heterogeneity and the presence of an immunosuppressive milieu. In order to understand the complex gene expression patterns and cell interactions in GCTB, we carried out a thorough investigation using single-cell RNA sequencing (scRNA-seq). We examined scRNA-seq data from 7091 cells that were collected after surgical removal of GCTB. Following the initial quality control process, 10 separate groups of cells were distinguished, which consisted of dendritic cells, endothelial cells, macrophage cells, mast cells, monocyte cells, neutrophil cells, tumor cells, osteoclast cells, pericyte cells, and T cells. Additional analysis uncovered distinct categories within tumor-associated macrophages (TAMs), CD8+ T cells, and CD4+ T cells. The differentiation mechanisms of TAMs, CD8+ T cells, and CD4+ T cells were explored using pseudo-time trajectory analysis. The CellPhoneDB study revealed the interactions between various cell types within the TME of GCTB. TAMs have been identified as the main infiltrating cells in GCTB. These TAMs exhibit several subtypes that are characterized by specific marker genes and functional states. The identification of several subgroups within CD8+ T cells that are involved in regulating immunological checkpoints underscores the difficulties encountered when attempting to employ immune checkpoint blockade therapy for GCTB. T cell exhaustion poses a major barrier to the efficacy of antitumor immune responses. Research suggests a strong correlation between TAMs and exhausted T cells (Texs) in the TME. The high number of regulatory T cells (Tregs) highlights the immunosuppressive nature of the immunological environment in GCTB. Significant interactions have been observed between TAMs and tumor cells, highlighting their crucial involvement in immune evasion strategies. This scRNA-seq study provides a general overview of the different cellular compositions and immune interactions within GCTB. The identified subtypes and communication networks provide valuable information about the immunosuppressive environment of GCTB, laying the foundation for prospective therapeutic approaches targeting specific cell types or interactions.

Giant-cell tumour (GCT) of bone is a primary osteolytic bone tumour with low metastatic potential and is associated with substantial skeletal morbidity. GCT is rich in osteoclast-like giant cells and contains mononuclear (stromal) cells that express RANK ligand (RANKL), a key mediator of osteoclast activation. We investigated the potential therapeutic effect of denosumab, a fully human monoclonal antibody against RANKL, on tumour-cell survival and growth in patients with GCT. In this open-label, single-group study, 37 patients with recurrent or unresectable GCT were enrolled and received subcutaneous denosumab 120 mg monthly (every 28 days), with loading doses on days 8 and 15 of month 1. The primary endpoint was tumour response, defined as elimination of at least 90% of giant cells or no radiological progression of the target lesion up to week 25. Study recruitment is closed; patient treatment and follow-up are ongoing. The study is registered with Clinical Trials.gov, NCT00396279. Two patients had insufficient histology or radiology data for efficacy assessment. 30 of 35 (86%; 95% CI 70–95) of evaluable patients had a tumour response: 20 of 20 assessed by histology and 10 of 15 assessed by radiology. Adverse events were reported in 33 of 37 patients; the most common being pain in an extremity (n=7), back pain (n=4), and headache (n=4). Five patients had grade 3–5 adverse events, only one of which (grade 3 increase in human chorionic gonadotropin concentration not related to pregnancy) was deemed to be possibly treatment related. Five serious adverse events were reported although none were deemed treatment related. Further investigation of denosumab as a therapy for GCT is warranted. Amgen, Inc.