The Role of Bone Grafting vs. Bone Cement in the Treatment of Giant Cell Tumor of Bone: A Systematic Review and Meta-Analysis on the Risk of Recurrence in 1,454 Patients.

BACKGROUND: Giant cell tumor of bone (GCTB) presents a challenge in management due to its invasive nature and propensity for local recurrence. While either bone grafting (BG) or bone cement (BC) can be utilized to fill defects after intralesional curettage, the optimal treatment remains contested. The purpose of this study was to examine the impact of defect filling with BC compared with BG on recurrence rates in patients with GCTB following intralesional curettage. METHODS: A random-effects model binary outcome meta-analysis was performed utilizing recurrence rate for the BC and BG groups to evaluate the risk ratio (p < 0.05 considered significant). There were 1,454 patients included. RESULTS: Intralesional curettage with BG had a recurrence risk ratio of 1.68 (95% confidence interval [CI], 1.22-2.31, p = 0.001) when compared with BC. The overall rate of recurrence for GCTB after intralesional curettage with BC was 20.05% vs. 29.74% with BG (95% CI, 0.17-0.23 vs. 0.26-0.33, p < 0.001). CONCLUSION: Intralesional curettage with BC for the treatment of GCTB demonstrated lower recurrence rates than intralesional curettage with BG. However, the rates of recurrence remain substantial for both groups, necessitating careful consideration of the benefits and potential pitfalls associated with BC vs. BG when considering salvage options after recurrences. LEVEL OF EVIDENCE: Level III. See Instructions for Authors for a complete description of levels of evidence.

Lymphocyte Infiltration Score and Spatial Characteristics Refined the Prognosis and Denosumab Treatment Responsiveness Indicators for Giant Cell Tumor of Bone.

PURPOSE: The prognostic value of lymphocyte infiltration score (LIS) and its nearest neighbor distance to tumor cells (NNDTC) in giant cell tumor of bone (GCTB) is currently not well established. This study aims to characterize LIS and NNDTC and examine their correlation with denosumab treatment responsiveness, clinicopathologic features, and patient prognosis. METHODS: Using multiplexed quantitative immunofluorescence, LIS was evaluated in 253 tumor specimens, whereas NNDTC was computed using HALO software. Subsequently, we analyzed the association of these parameters with patient outcomes (progression-free survival [PFS] and overall survival [OS]), clinicopathologic features, and denosumab treatment responsiveness. RESULTS: Low LIS was indicative of both poor PFS and OS (both P < .001). In addition, LIS was significantly associated with sex (P = .046), Enneking staging (P < .001), Ki-67 expression (P = .007), and denosumab treatment responsiveness (P = .005). Lower CD8+ (tumor interior [TI]) NNDTC, and CD3+ (TI) NNDTC were associated with worse PFS (P = .003 and .038, respectively), whereas lower CD8+ (TI) NNDTC was associated with worse OS (P = .001), but CD8+ (tumor infiltrating margin) NNDTC had the opposite effect (P = .002). Moreover, NNDTC showed a correlation with several clinicopathologic features. Importantly, LIS outperformed Enneking and Campanacci staging systems in predicting the clinical outcomes of GCTB. CONCLUSION: These findings suggest that LIS is a reliable predictive tool for clinically relevant outcomes and response to denosumab therapy in patients with GCTB. These parameters may prove to be useful in guiding prognostic risk stratification and therapeutic optimization for patients.

Validity of the Musculoskeletal Tumor Society Score for lower extremity in patients with bone sarcoma or giant cell tumour of bone undergoing bone resection and reconstruction surgery in hip and knee.

BACKGROUND: The Musculoskeletal Tumor Society Score (MSTS) is widely used to evaluate functioning following surgery for bone and soft-tissue sarcoma. However, concerns have been raised about its content validity due to the lack of patient involvement during item development. Additionally, literature reports inconsistent results regarding data quality and structural validity. This study aimed to evaluate content, structural and construct validity of the Danish version of the MSTS for lower extremity (MSTS-LE). METHODS: The study included patients from three complete cohorts (n = 87) with bone sarcoma or giant cell tumour of bone who underwent bone resection and reconstruction surgery in hip and knee. Content validity was evaluated by linking MSTS items to frameworks of functioning, core outcome sets and semi-structured interviews. Data quality, internal consistency and factor analysis were used to assess the underlying structure of the MSTS. Construct validity was based on predefined hypotheses of correlation between the MSTS and concurrent measurements. RESULTS: Content validity analysis revealed concerns regarding the MSTS. The MSTS did not sufficiently cover patient-important functions, the item Emotional acceptance could not be linked to the framework of functioning, the items Pain and Emotional acceptance pertained to domains beyond functioning and items' response options did not match items. A two-factor solution emerged, with the items Pain and Emotional acceptance loading highly on a second factor distinct from functioning. Internal consistency and construct validity showed values below accepted levels. CONCLUSION: The Danish MSTS-LE demonstrated inadequate content validity, internal consistency, and construct validity. In addition, our analyses did not support unidimensionality of the MSTS. Consequently, the MSTS-LE is not a simple reflection of the construct of functioning and the interpretation of a sum score is problematic. Clinicians and researcher should exercise caution when relying solely on MSTS scores for assessing lower extremity function. Alternative outcome measurements of functioning should be considered for the evaluation of postoperative function in this patient group.

The tumor-stroma ratio in giant cell tumor of bone: associations with the immune microenvironment and responsiveness to denosumab treatment.

BACKGROUND: Currently, there is limited understanding regarding the clinical significance of the tumor-stroma ratio (TSR) in giant cell tumor of bone (GCTB). Hence, we aimed to investigate the distribution of TSR in GCTB and explore its correlation with various clinicopathologic factors, immune microenvironment, survival prognosis, and denosumab treatment responsiveness. METHODS: We conducted a multicenter cohort study comprising 426 GCTB patients treated at four centers. TSR was evaluated on hematoxylin and eosin-stained and immunofluorescent sections of tumor specimens. Immunohistochemistry was performed to assess CD3+, CD4+, CD8+, CD20+, PD-1+, PD-L1+, and FoxP3+ TIL subtypes as well as Ki-67 expression levels in 426 tissue specimens. These parameters were then analyzed for their correlations with patient outcomes [local recurrence-free survival (LRFS) and overall survival (OS)], clinicopathological features, and denosumab treatment responsiveness. RESULTS: Low TSR was significantly associated with poor LRFS and OS in both cohorts. Furthermore, TSR was also correlated with multiple clinicopathological features, TIL subtype expression, and denosumab treatment responsiveness. TSR demonstrated similar predictive capabilities as the conventional Campanacci staging system for predicting patients' LRFS and OS. CONCLUSION: The results of this study provide evidence supporting the use of TSR as a reliable prognostic tool in GCTB and as a predictor of denosumab treatment responsiveness. These findings may aid in developing individualized treatment strategies for GCTB patients in the future.

The diagnostic and prognostic value of tartrate-resistant acid phosphatase isoform 5b for giant cell tumor of bone.

BACKGROUND: Serum level of tartrate-resistant acid phosphatase 5b (TRACP5b) is an excellent serum marker of bone resorption. In patients with giant cell tumor of bone (GCTB), TRACP5b levels are reportedly elevated. This study investigated whether TRACP5b could be a diagnostic serum marker and be useful for detecting postoperative disease progression for GCTB. METHODS: Cohort 1: We abstracted data from 120 patients with TRACP5b measurements from our database: 49 patients with GCTB and 71 patients non-GCTB. We compared serum TRACP5b values between the GCTB and non-GCTB groups. Cohort 2 included 47 patients with GCTB who had more than 6 months of follow-up and multiple TRACP5b values. For patients with local recurrence, TRACP5b change rate was calculated by comparing the TRACP5b value just before progression (a) with the value at the time of progression (b): Change rate = [(b)-(a)]/(a). In the non-progression group, the change rate was calculated from the two consecutive TRACP5b values, (c) and (d): Change rate =[(c)-(d)]/(c). We compared TRACP5b change rates between the progression and non-progression groups. RESULTS: Cohort 1: The GCTB group had a significantly higher mean TRACP5b value (1756 ± 2021 mU/dL) than the non-GCTB group (415 ± 219 mU/dL) (p < 0.0001). Cohort 2: The mean TRACP5b change rate of the progression group was significantly higher than the non-progression group (8.53 ± 8.52 and 0.24 ± 0.27, respectively; p < 0.0001). CONCLUSION: TRACP5b is a useful diagnostic marker in GCTB. The rate of change in serum TRACP5b values is a highly sensitive marker for predicting local recurrence in GCTB.

Giant cell tumor of femur with single pulmonary metastasis - yet another curative oligometastasis.

ABSTRACT: Giant cell tumor of bone (GCT) is a benign tumor of bone that is known to be locally aggressive rarely metastasizing to distant sites, most commonly to the lungs. The reported pulmonary metastasis incidence is 1 - 9%. We report a case of GCT with solitary pulmonary metastasis who had significant clinical benefit and disease control with sequential application of surgical resection of pulmonary metastasis, local external beam radiation therapy (EBRT), and systemic Denosumab. We wish to highlight that even in metastatic GCT, there is significant clinical benefit in aggressive treatment.

The effect of preoperative embolization on giant cell tumors of the bone localized in the iliosacral region of the pelvis.

INTRODUCTION: Giant cell tumors of the bone (GCTB) are aggressive neoplasms, with rare occurrences in the posterior pelvis and sacral area. Surgical challenges in this region include the inability to apply a tourniquet and limited cementation post-curettage due to proximity to neurovascular structures, leading to potential complications. This case-control study explores the impact of preoperative embolization on GCTB located in the iliosacral region. METHODS: Five surgeries (January-December 2021) for pelvic GCTB (3 sacrum, 2 posterior ilium) were performed on four patients. Diagnosis was confirmed through preoperative CT-guided biopsies. One surgery involved curettage with PMMA cement filling, while four surgeries had curettage without cavity filling. Preoperative embolization of the tumor feeding vessel occurred approximately 16 h before surgery in two cases. Denosumab treatment was not administered. RESULTS: Tumor volume, assessed by preoperative MRI, was comparable between patients with and without preoperative embolization (p = .14). Surgeries without embolization had a mean intraoperative blood loss of 3250 ml, erythrocyte transfusion volume of 1125 ml, and a mean surgical time of 114.5 min for two surgeries. Surgeries with preoperative embolization showed a mean intraoperative blood loss of 1850 ml, no erythrocyte transfusion requirement, and a mean surgical time of 68 min. CONCLUSION: Curettage of GCTB in the posterior pelvis and sacrum presents challenges, with significant intraoperative blood loss impacting surgical time and transfusion needs. Preoperative embolization may be beneficial in reducing blood loss during surgery in these cases.

Periprosthetic giant cell tumour of the tibia: en bloc resection and megaprosthesis revision.

We present a case detailing the diagnosis and management of a periprosthetic giant cell tumour in a female patient in her 70s, who had undergone total knee arthroplasty (TKA) for primary osteoarthritis in her right knee 7 years prior. The patient reported 4 months of painful weight-bearing. Various imaging modalities, including plain radiographs, CT scans and MRI, revealed a sizeable lytic lesion beneath the TKA prosthesis, along with loosening of the tibial component.Blood tests and analyses of synovial fluid ruled out periprosthetic joint infection, and a biopsy confirmed the diagnosis of a giant cell tumour of the bone. Treatment entailed en bloc resection of the tumour and revision of the TKA using a hinged, oncological-type megaprosthesis. Surgical procedures involved careful resection of the proximal tibia, preservation of vasculature and the creation of a medial gastrocnemius muscle flap. Following surgery, the patient underwent supervised rehabilitation with a functional brace.

H3.3-G34W in giant cell tumor of bone functionally aligns with the exon choice repressor hnRNPA1L2.

RNA processing is an essential post-transcriptional phenomenon that provides the necessary complexity of transcript diversity prior to translation. Aberrations in this process could contribute to tumourigenesis, and we have previously reported increased splicing alterations in giant cell tumor of bone (GCTB), which carries mutations in the histone variant H3.3 encoding glycine 34 substituted for tryptophan (H3.3-G34W). G34W interacts with several splicing factors, most notably the trans-acting splicing factor hnRNPA1L2. To gain a deeper understanding of RNA processing in GCTB and isogenic HeLa cells with H3.3-G34W, we generated RNA-immunoprecipitation sequencing data from hnRNPA1L2 and H3.3-G34W associated RNAs, which showed that 80% overlapped across genic regions and were frequently annotated as E2F transcription factor binding sites. Splicing aberrations in both GCTB and HeLa cells with H3.3-G34W were significantly enriched for known hnRNPA1L2 binding motifs (p value < 0.01). This splicing aberration differed from hnRNPA1L2 knockouts, which showed alterations independent of H3.3-G34W. Of functional significance, hnRNPA1L2 was redistributed to closely match the H3.3 pattern, likely driven by G34W, and to loci not occupied in normal parental cells. Taken together, our data reveal a functional overlap between hnRNPA1L2 and H3.3-G34W with likely significant consequences for RNA processing during GCTB pathogenesis. This provides novel opportunities for therapeutic intervention in future modus operandi.

Diaphyseal giant cell tumour of mid-shaft tibia.

SummaryGiant cell tumours of bone are benign and locally aggressive tumours that usually occur in young adults and at the epiphysial locations after physeal closure. Occurrence outside of epiphysial locations and appearance in geriatric patients is rare. We report a case of a woman in her late 60s with a giant cell tumour of the mid-shaft of the right tibia. Extended curettage and biological reconstruction were performed with autologous double-barrel fibular struts and tri-cortical iliac crest bone grafting. At the 28-month follow-up examination, we noted full bony union at both ends with successful consolidation of the fibular struts, and importantly, no evidence of recurrence or other complications was observed.

Establishment and characterization of two novel patient-derived cell lines from giant cell tumor of bone: NCC-GCTB8-C1 and NCC-GCTB9-C1.

Giant cell tumor of bone (GCTB) is a rare osteolytic bone tumor consisting of mononuclear stromal cells, macrophages, and osteoclast-like giant cells. Although GCTB predominantly exhibits benign behavior, the tumor carries a significant risk of high local recurrence. Furthermore, GCTB can occasionally undergo malignant transformation and distal metastasis, making it potentially fatal. The standard treatment is complete surgical resection; nonetheless, an optimal treatment strategy for advanced GCTB remains unestablished, necessitating expanded preclinical research to identify appropriate therapeutic options. However, only one GCTB cell line is publicly available from a cell bank for research use worldwide. The present study reports the establishment of two novel cell lines, NCC-GCTB8-C1 and NCC-GCTB9-C1, derived from the primary tumor tissues of two patients with GCTB. Both cell lines maintained the hallmark mutation in the H3-3A gene, which is associated with tumor formation and development in GCTB. Characterization of these cell lines revealed their steady growth, spheroid-formation capability, and invasive traits. Potential therapeutic agents were identified via extensive drug screening of the two cell lines and seven previously established GCTB cell lines. Among the 214 antitumor agents tested, romidepsin, a histone deacetylase inhibitor, and mitoxantrone, a topoisomerase inhibitor, were identified as potential therapeutic agents against GCTB. Conclusively, the establishment of NCC-GCTB8-C1 and NCC-GCTB9-C1 provides novel and crucial resources that are expected to advance GCTB research and potentially revolutionize treatment strategies.

Immunohistochemical expression of H3.3 G34W in 100 giant cell tumors of bone and its diagnostic mimics, including its value in resolving uncommon diagnostic scenarios: A single institutional study at a tertiary cancer referral center, India.

BACKGROUND: There can be a diagnostic challenge in differentiating giant cell tumor of bone (GCTB) from its mimics. Lately, histone H 3 F 3 A (Histone 3.3 ) G34W has been identified as a promising immunohistochemical marker. AIMS: This study was aimed at evaluating H3.3 G34W immunostaining in 100 GCTBs, including its value in resolving diagnostic dilemmas. MATERIALS AND METHODS: Immunohistochemical staining for H3.3 G34W was graded in terms of staining intensity (1+ to 3+) and the percentage of tumor cells showing crisp nuclear staining. RESULTS: One hundred GCTBs occurred in 58 males and 42 females (M: F ratio = 1.3), of 7-66 years age (average = 31.3, median = 28), commonly in distal femur (26), followed by proximal tibia (17), distal radius (12), proximal humerus (7), metacarpals (7), sacrum (6), proximal fibula (6), and relatively unusual sites (19), including a single multicentric case. Out of 92 GCTBs, wherein H3.3 G34W immunostaining worked, 81 (88.1%) showed positive staining in the mononuclear cells, including tumors with fibrous histiocytoma-like areas, sparing osteoclast-like giant cells, with 3+ staining intensity in 65/81 (80%) tumors. All 7/7 (100%) malignant GCTBs showed positive staining, including the pleomorphic/sarcomatous cells. All 7/7 (100%) metastatic GCTBs showed positive immunostaining. Seven out of 10 post-denosumab treated GCTBs showed positive H3.3 G34W immunostaining in the residual mononuclear cells. None of the other 37 "giant cell-rich" lesions displayed H3.3 G34W immunostaining. Four of 9 GCTBs tested for H3.3 G34W mutation showed positive results. CONCLUSIONS: The diagnostic sensitivity and specificity of H3.3 G34W for GCTB were 88.1% and 100%, respectively. This constitutes one of the first reports from our country, further validating the diagnostic value of H3.3 G34W in differentiating GCTB, including metastatic and malignant forms from its mimics, including small biopsy samples. Its value in various diagnostic dilemmas is presented and utility in identifying residual tumor cells in post-denosumab treated GCTBs is worth exploring.

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.

Malignant giant cell tumour of distal ulna.

Giant cell tumour (GCT) accounts for 5% of all primary bone tumours. GCT in the distal third of ulna is quite rare. We present a case of recurrent GCT in distal third of ulna with malignant features involving tenosynovium. The case was treated by wide resection of tumour and on follow up, patient recovered well with no evidence of further recurrence. Considering the features, according to the literature reviewed, is the first case of its type.

Histones and their practical application in bone tumors: Do I always need them?

Historically, the diagnosis of giant cell-rich neoplasms arising in bone has been challenging owing to overlapping clinical and radiographic findings resulting in the difficult separation of several neoplasms, particularly when biopsy material is limited. However, with the discovery of the driver histone mutations in giant cell tumor of bone (GCTB) and chondroblastoma, as well as USP6 rearrangements in aneurysmal bone cyst, pathologists now have objective ancillary tools to aid in the separation of several histologically similar giant cell-rich neoplasms. Furthermore, the recognition of histone mutations has allowed pathologists to revisit several entities, such as "malignant chondroblastoma," and furthered our understanding of phenomena such as "aneurysmal bone cyst-like change," formerly recognized as "secondary aneurysmal bone cyst." Herein, the evolution of testing for histone mutations in bone tumors is considered; the sensitivity and specificity of the histone antibodies is reviewed; and a practical guide for the use of these ancillary tests is offered.

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.

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.

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.

Does the use of polymethyl-methacrylate cement after intralesional curettage of giant cell tumors of appendicular bone guarantee reduced local recurrence rates? A retrospective analysis.

PURPOSE: Polymethyl-methacrylate cement (PMMA) is often used as bone defect reconstruction material after surgical removal of giant cell tumors. The purpose of this study was to investigate if the application of PMMA improves the local recurrence rates for giant cell tumors (GCT) of appendicular bone treated with intralesional curettage. METHODS: A retrospective analysis of all appendicular GTCs treated at two major Danish sarcoma centres between the 1st of January 1998 and December 31st 2013; minimum follow-up of 3.0 years (median: 8.9; 1.3-18.7 years). Kaplan-Meier survival model, log-rank and multivariate Cox regression were used to calculate and compare local recurrence rates. p-values <0.05 were considered statistically significant. RESULTS: 102 patients (M59/F43), median age 31Y (11-84) were included in this study. The overall 3-years local recurrence-rate was 19.9% (95%CI: 11.9-27.9%); 91% had occurred within 3 years. In patients treated with intralesional curettage (n = 64), the 3-years recurrence-rate was 30.6% (95%CI: 18.8-42.4%), compared to 2.6% (95%CI: 0.0-7.8%) in patients treated with wide resection or amputation (n = 38), p < .001. The 3-years recurrence-rate for patients treated with intralesional curettage and reconstruction using PMMA was 29.0% (95%CI: 12.6-45.4%) and without PMMA: 31.8% (95%CI: 15.2-48.4%), p = .83. CONCLUSION: We found that the use of PMMA for bone defect reconstruction after intralesional curettage of GTCs in the appendicular skeleton did not ensure a reduced risk of local recurrence.