Background: Giant cell tumors (GCTs) are locally aggressive but rarely malignant bone neoplasms that uncommonly involve the skull. In this report, we describe a tumor of the sphenoid sinus. Case presentation: A 51-year-old female was presented with headache, and bilateral decreased visual acuity, CT scan, and brain MRI revealed an infra-sellar enhancing tumor expanding to the sellar and supra-sellar region which proved to be a GCT. the patient had received 03 months of preoperative denosumab-based treatment and imaging follow-up showed regression in size and morphology modifications of tumor tissue. Conclusion: This is one of few reports to describe the appearance of sphenoid bone GCT, and the first report to highlight the effects of short-term denosumab treatment in GCTb in such a location.

UNASSIGNED: Giant-cell tumor of bone (GCTB) is a relatively benign, but locally aggressive osteoclastogenic stromal tumour of the bone. Although denosumab has been approved as an monoclonal antibody against RANK ligand for the treatment of GCTB, few clinical trials of the benefit in tumor response have been conducted to prove the efficiency in Chinese population.
UNASSIGNED: In this multicentric, random controlled, clinical trial, 160 patients were enrolled to compare the therapeutic efficacy and safety of denosumab and zoledronic acid treatment in patients with surgically unsalvageable GCTB.
UNASSIGNED: Between 2nd Jan 2015 and 1st Jan 2018, 160 adults (aged ≥ 18 years) with ①surgically unsalvageable GCTB, ②surgically salvageable GCTB with planned surgery expected to result in severe morbidity were included in this randomized clinical trial. Patients received either subcutaneous denosumab (DB group; 120 mg once every 4 weeks with loading doses of 120 mg subcutaneously admininstered on days 8 and 15; n = 80) or intravenous zoledronic acid (ZA group; 4 mg once every 4 weeks; n = 80) for six cycles. Disease status, clinical benefits, treatment-emergent adverse effects, overall survival, and cost of treatment were evaluated during the follow-up period. Statistical significance was determined using 95% confidence intervals.
UNASSIGNED: Denosumab and zoledronic acid had similar tumor responses (p = 0.118) and clinical benefits (p = 0.574). Disease progression was observed in fewer patients in the DB group (12.5%) than ZA group (15.0%). Denosumab caused fatigue (p = 0.001) and back pain (p < 0.0001), while zoledronic acid caused hypocalcemia (p < 0.0001), flu-like symptoms (p = 0.059) and hypotension (p = 0.059). Denosumab treatment was markedly more expensive than zoledronic acid treatment (p < 0.0001). The cost to manage treatment-emergent adverse effects was the same for the ZA group and the DB group (p = 0.425). The accumulate recurrence-free survival rate at 4-year follow-up is higher in DB group (p = 0.035).
UNASSIGNED: Denosumab is a safe but costly alternative to zoledronic acid for treatment of surgically unsalvageable GCTB.

Giant cell tumors of bone (GCTB) are associated with massive bone destructions and high recurrence rates. In a previous study, we observed cytotoxic effects of three different compositions of bioactive glasses (BGs) towards GCTSC but not bone marrow derived stromal cells (BMSC) indicating that BGs represent promising candidates for the development of new therapeutic approaches. In the current study we aimed to investigate the molecular mechanisms that are involved in BG induced cytotoxicity. We observed, that BG treatment was not associated with any signs of apoptosis, but rather led to a strong induction of mitogen activated protein kinases (MAPK) and, as a consequence, upregulation of several transcription factors specifically in GCTSC. Genome wide gene expression profiling further revealed a set of fifteen genes that were exclusively induced in GCTSC or induced significantly stronger in GCTSC compared to BMSC. BG treatment further induced autophagy that was significantly more pronounced in GCTSC compared to BMSC and could be inhibited by MAPK inhibitors. Together with the known osteogenic properties of BGs our findings support the suitability of BGs as therapeutic agents for the treatment of GCTB. However, these data have to be verified under in vivo conditions.

BACKGROUND: Giant cell tumor of bone (GCTB) is a locally aggressive bone tumor that represents about 4-5% of all primary bone tumors. It is characterized by aggressive growth, possible recurrence after surgical treatment and, in rare cases, metastasis. Surgical management is the primary treatment and may include intralesional curettage with adjuvants or, in rare cases, wide resection. In recent years the monoclonal antibody denosumab has been introduced as a potential (neo-)adjuvant systemic treatment option for patients with borderline resectable or unresectable lesions. Currently several studies reported that the use of denosumab prior to curettage possibly increase the risk of local recurrence.
METHODS: In this retrospective study we reviewed 115 cases of GCT with a mean follow-up of 65.6 (24-404) months who underwent a surgical treatment with or without preoperative denosumab therapy in our institution. Potential risk factors for LR and complications were analyzed.
RESULTS: The study includes 47 male (40.9%) and 68 female (59.1%) patients with a mean age of 33.9 (10-77) years and a mean follow-up of 65.6 (24-404) months. Denosumab was used in 33 (28.7%) cases, in 14 cases (12.2%) in a neoadjuvant setting and in 17 cases preoperatively before re-curettage (14.8%) after LR. In 105 cases (91.3%) an intralesional curettage was performed. The overall LR rate was 47.8% (55 cases). Patients who underwent intralesional curettage and bone cement augmentation without neoadjuvant denosumab treatment had LR in 42.2% (38/90) of the cases. Patients who underwent neoadjuvant denosumab treatment prior to curettage had LR in 28.6% (4/14). Re-recurrence was frequent in patients with neoadjuvant denosumab treatment who had LR after initial curettage (50%, 8/16). After wide resection and endoprosthetic replacement one case (20%) of local recurrence was detectable (1/5 cases).
CONCLUSIONS: GCTB recurs frequently after intralesional curettage and cement augmentation. While denosumab is a potential (neo-)adjuvant treatment option that might be used for lesions that are difficult to resect, surgeons should be aware that LR is still frequent.

UNASSIGNED: To determine if radiomics analysis based on preoperative computed tomography (CT) can predict early postoperative recurrence of giant cell tumor of bone (GCTB) in the spine.
UNASSIGNED: In a retrospective review, 62 patients with pathologically confirmed spinal GCTB from March 2008 to February 2018, with a minimum follow-up of 24 months, were identified. The mean follow-up was 73.7 months (range, 28.7-152.1 months). The clinical information including age, gender, lesion location, multi-vertebral involvement, and surgical methods, were obtained. CT images acquired before the operation were retrieved for radiomics analysis. For each case, the tumor regions of interest (ROI) was manually outlined, and a total of 107 radiomics features were extracted. The features were selected via the sequential selection process by using the support vector machine (SVM), then used to construct classification models with Gaussian kernels. The differentiation between recurrence and non-recurrence groups was evaluated by ROC analysis, using 10-fold cross-validation.
UNASSIGNED: Of the 62 patients, 17 had recurrence with a recurrence rate of 27.4%. None of the clinical information was significantly different between the two groups. Patients receiving curettage had a higher recurrence rate (6/16 = 37.5%) compared to patients receiving TES (6/26 = 23.1%) or intralesional spondylectomy (5/20 = 25%). The final radiomics model was built using 10 selected features, which achieved an accuracy of 89% with AUC of 0.78.
UNASSIGNED: The radiomics model developed based on pre-operative CT can achieve a high accuracy to predict the recurrence of spinal GCTB. Patients who have a high risk of early recurrence should be treated more aggressively to minimize recurrence.

UNASSIGNED: The present study aimed to evaluate the short-term clinical feasibility and efficacy of the minimally invasive endoscopic technique (MIET) for the treatment of symptomatic benign bone lesions.
UNASSIGNED: This single-institution retrospective study investigated 34 patients with symptomatic benign bone lesions from December 2015 to June 2017. Patients involved in this study presented with definite indications for surgical intervention. All procedures were performed under endoscopic guidance for direct visualization followed by complete curettage of tumor tissue. There were 19 males and 15 females, with a mean age of 33.3 ± 12.7 years (range, 17-68 years). The lesions were located in the upper extremities (20, 58.8%), lower extremities (9, 26.5%) and pelvis (5, 14.7%). Primary outcomes were measured before and after intervention using the visual analog scale (VAS), the Musculoskeletal Tumor Society (MSTS) stage and the 36-item Short-Form Health Survey (SF-36) scoring system.
UNASSIGNED: Of the 34 patients included in this study, all completed follow-up examinations, with a mean follow-up duration of 22.4 ± 7.6 months (range, 13-35 months). Significantly improved VAS, MSTS and SF-36 scores were observed at 3 months after the initial treatment (P < 0.001), suggesting enhanced pain relief and improved functional recovery and quality of life following surgery. All procedures were technically successful, with the exception of 3 cases (8.8%) manifesting access site numbness; these patients recovered within the follow-up period through symptomatic treatment alone. Only 2 patients (5.9%; one osteoblastoma and one enchondroma) experienced local recurrence and underwent standard open curettage within the follow-up period. All patients showed functional stability without any major complications.
UNASSIGNED: The MIET is an effective and safe alternative treatment for symptomatic benign bone lesions. The short-term efficacy of MIET was favorable and associated with improved pain palliation, quality of life and functional recovery.

BACKGROUND: Although denosumab has been approved as an antiresorptive agent for giant cell tumor of bone, its efficacy has not been proven.
OBJECTIVE: To compare the efficacy and safety of denosumab and zoledronic acid treatment in patients with surgically unsalvageable giant cell tumor of bone.
METHODS: A total of 250 patients with surgically unsalvageable giant cell tumor of bone were included in this randomized clinical trial. Patients received either subcutaneous denosumab (DB group; 120 mg per 4 weeks plus an additional 120 mg on days 8 and 15; n = 125) or intravenous zoledronic acid (ZA group; 4 mg per 4 weeks; n = 125) for six cycles. Disease status, clinical benefits, treatment-emergent adverse effects, overall survival, and cost of treatment were evaluated during the follow-up period. Statistical significance was determined using 95% confidence intervals.
RESULTS: Denosumab and zoledronic acid had similar tumor responses (p = 0.18) and clinical benefits (p = 0.476). Disease progression was observed in fewer patients in the DB group (1%) than ZA group (2%). Denosumab caused fatigue (p = 0.0004) and back pain (p < 0.0001), while zoledronic acid caused hypocalcemia (p < 0.0001), flu-like symptoms (p = 0.021), hypotension (p = 0.021), and hypokalemia (p = 0.021). Denosumab treatment was markedly more expensive than zoledronic acid treatment (p < 0.0001). The cost to manage treatment-emergent adverse effects was higher for the ZA group than the DB group (p = 0.0425). Overall survival was the same for both treatments (p = 0.066).
CONCLUSIONS: Denosumab is a safe but costly alternative to zoledronic acid for treatment of surgically unsalvageable giant cell tumor of bone.

Receptor activator of nuclear factor kappa-B ligand (RANKL) is an essential mediator of osteoclast formation, function and survival. In patients with solid tumor metastasis to the bone, targeting the bone microenvironment by inhibition of RANKL using denosumab, a fully human monoclonal antibody (mAb) specific to RANKL, has been demonstrated to prevent tumor-induced osteolysis and subsequent skeletal complications. Recently, a prominent functional role for the RANKL pathway has emerged in the primary bone tumor giant cell tumor of bone (GCTB). Expression of both RANKL and RANK is extremely high in GCTB tumors and denosumab treatment was associated with tumor regression and reduced tumor-associated bone lysis in GCTB patients. In order to address the potential role of the RANKL pathway in another primary bone tumor, this study assessed human RANKL and RANK expression in human primary osteosarcoma (OS) using specific mAbs, validated and optimized for immunohistochemistry (IHC) or flow cytometry. Our results demonstrate RANKL expression was observed in the tumor element in 68% of human OS using IHC. However, the staining intensity was relatively low and only 37% (29/79) of samples exhibited≥10% RANKL positive tumor cells. RANK expression was not observed in OS tumor cells. In contrast, RANK expression was clearly observed in other cells within OS samples, including the myeloid osteoclast precursor compartment, osteoclasts and in giant osteoclast cells. The intensity and frequency of RANKL and RANK staining in OS samples were substantially less than that observed in GCTB samples. The observation that RANKL is expressed in OS cells themselves suggests that these tumors may mediate an osteoclastic response, and anti-RANKL therapy may potentially be protective against bone pathologies in OS. However, the absence of RANK expression in primary human OS cells suggests that any autocrine RANKL/RANK signaling in human OS tumor cells is not operative, and anti-RANKL therapy would not directly affect the tumor.