Argon Beam Coagulation as an Adjuvant for Extended Curettage for Giant Cell Tumors of the Bone: A Study of 50 Cases / Coagulação por plasma de argônio como adjuvante à curetagem estendida em tumores de células gigantes do osso: Um estudo de 50 casos

Abstract Objective Extended curettage with adjuvants of giant cell tumors of bone is associated with a lower rate of recurrence of the tumor while preserving the adjacent joint. The present study was conducted to estimate the recurrence rate and functional outcome after using argon beam as an adjuvant for extended curettage. Methods We selected 50 patients with giant cell tumors, meeting all the inclusion criteria, who underwent extended curettage using high speed burr and argon beam photocoagulation between July 2016 to January 2019. On their follow-up visit, they were assessed for any complaints of pain and signs like tenderness, locally raised temperature, and decreased range of motion of the adjacent joint. Radiologically, the patients were assessed for any increased lucency around the cement mantle and uptake of the subarticular graft. Musculoskeletal Tumor Society Score (MSTS) was administered to the patients, and range of motion of the adjacent joint was compared with the contralateral joint. Results Recurrence was found in 4 patients, that is, an 8% recurrence rate. Twenty-six out of 28 patients with a tumor in the lower limb had a grade-5 weight bearing status 6 months from the surgery, and their range of motion was comparable to contralateral healthy joint with an average MSTS score of 27 (18-30). Conclusion Extended curettage of giant cell tumors using argon beam coagulation is associated with low recurrence rates of the tumor and is an effective modality in the treatment of these tumors besides having a functional outcome comparable to the healthy limb.

Resumo Objetivo A curetagem estendida com adjuvantes de tumores de células gigantes do osso está associada a uma menor taxa de recidiva da neoplasia e à preservação da articulação adjacente. Este estudo foi feito para estimar a taxa de recidiva e o resultado funcional após o uso de plasma de argônio como adjuvante à curetagem estendida. Métodos Cinquenta pacientes com tumores de células gigantes que atendiam a todos os critérios de inclusão foram selecionados para o estudo e submetidos à curetagem estendida com broca de alta velocidade e fotocoagulação com plasma de argônio entre julho de 2016 e janeiro de 2019. À consulta de acompanhamento, os pacientes foram avaliados quanto a quaisquer queixas de dor e sinais como sensibilidade, aumento local da temperatura e diminuição da amplitude de movimento da articulação adjacente. Radiologicamente, os pacientes foram avaliados quanto à presença de qualquer aumento de radiotransparência ao redor do manto de cimento e incorporação do enxerto subarticular. O questionário Musculoskeletal Tumor Society Score (MSTS) foi administrado aos pacientes e a amplitude de movimentação da articulação adjacente foi comparada à articulação contralateral. Resultados Quatro pacientes apresentaram recidiva, o que corresponde a uma taxa de 8%. Seis meses após a cirurgia, 26 de 28 pacientes com tumor no membro inferior tinham capacidade de sustentação de peso de grau 5 e amplitude de movimento comparável à articulação saudável contralateral, com pontuação MSTS média de 27 (intervalo de 18 a 30). Conclusão A curetagem estendida de tumores de células gigantes com coagulação por plasma de argônio está associada a baixas taxas de recidiva da neoplasia; é uma modalidade eficaz no tratamento desses tumores e o resultado funcional é comparável ao do membro saudável.

Radiological Assessment of Giant Cell Tumour of Bone in the Sacrum: From Diagnosis to Treatment Response Evaluation.

Giant cell tumour of bone (GCTB) typically occurs in young adults from 20-40 years old. Although the majority of lesions are located in the epi-metaphyses of the long bones, approximately one third of tumours are located in the axial skeleton, of which only 4% in the sacrum. Sacral tumours tend to be large at the time of presentation, and they present with aggressive features such as marked cortical destruction and an associated soft tissue component. The 2020 World Health Organisation classification of Soft Tissue and Bone Tumours describes GCTB as a neoplasm which is locally aggressive and rarely metastasizing. The tumour contains three different cell types: neoplastic mononuclear stromal cells, macrophages and osteoclast-like giant cells. Two tumour subtypes were defined: conventional GCTB and malignant GCTB. Only 1-4% of GCTB is malignant. In this review article, we will discuss imaging findings at the time of diagnosis to guide the musculoskeletal radiologist in reporting these tumours. In addition, imaging for response evaluation after various treatment options will be addressed, such as surgery, radiotherapy, embolization and denosumab. Specific findings will be presented per imaging modality and illustrated by cases from our tertiary sarcoma referral center. Common postoperative and post-radiotherapy findings in GCTB of the sacrum on MRI will be discussed.

[Giant cell tumor of bone]. / Tumeur à cellules géantes de l'os.

Giant cell tumor is a benign epiphyseo-metaphyseal bone tumor affecting the young patient. It is characterized by an extensive osteolysis, a high potential for recurrence, a risk of malignant transformation and pulmonary metastases. Curettage and cavity filling is the most common treatment, even in the case of a pathological fracture. A wide resection with prosthetic reconstruction must sometimes be considered. Better knowledge of the role of RANK-L in the pathophysiology of these tumors has led to clinical trials involving denosumab. Treatment with denosumab is suggested for inoperable lesions, or for aggressive lesions, in particular of the spine, pelvis, and sacrum before en bloc resection.

La tumeur à cellules géantes est une tumeur osseuse bénigne épiphysométaphysaire touchant le sujet jeune. Elle est caractérisée par une ostéolyse parfois extensive, un potentiel de récidive élevé, un risque de transformation maligne et de métastases pulmonaires. Le curetage-comblement est le traitement de choix, y compris en cas de fracture pathologique. Une résection plus large avec reconstruction prothétique doit parfois être envisagée. La meilleure connaissance du rôle de RANK-L dans la physiopathologie de ces tumeurs a conduit à des essais cliniques impliquant le dénosumab. Un traitement par celui-ci est proposé pour les lésions inopérables ou agressives, notamment du rachis, du pelvis et du sacrum, avant une résection en bloc.

Update and interpretation of 2021 National Comprehensive Cancer Network (NCCN) "Clinical Practice Guidelines for Bone Tumors"

The incidence of primary malignant bone tumors is low, and clinical cognition is insufficient. The establishment of diagnostic criteria is of great significance for prognosis of tumors. National Comprehensive Cancer Network (NCCN) regularly publishes "Clinical Practice Guidelines for Bone Tumors" to summarize the latest treatment progress of bone tumors. In the latest version of the guidelines released in November 2020, surgery is the main treatment for chondrosarcoma, chordoma, and giant cell tumor of bone, which can be combined with radiotherapy or targeted therapy. Ewing's sarcoma and osteosarcoma are treated by surgery combined with chemotherapy. Immunotherapy can be used to treat high-grade undifferentiated pleomorphic sarcoma. For recurrent tumors, surgery combined with radiotherapy, chemotherapy, and/or targeted therapy can be used for control. The guidelines provide a reference for the standard treatment of bone tumors.

Selective and caspase-independent cytotoxicity of bioactive glasses towards giant cell tumor of bone derived neoplastic stromal cells but not to bone marrow derived stromal cells.

Semi-malignant giant cell tumors of bone (GCTB) are associated with large osteolytic defects and significant bone destructions. Surgical resection remains the standard therapy that is, however, associated with very high recurrence rates. Bioactive glasses (BGs) that are osteogenic but under certain conditions also cytotoxic might be suitable to achieve biological reconstruction with simultaneous reduction of tumor recurrence in GCTB. In this study, a concentration and time dependent cytotoxic effect of five different BG compositions towards neoplastic GCTB cells was identified while bone marrow derived mesenchymal stromal cells were mostly unaffected. Time course and extent of the cytotoxic effect were dependent on the BG composition and were not associated with caspases activation, indicating that apoptotic mechanisms are not involved. Rather, detection of BG-induced disruption of the cell membranes and a rapid drop of intracellular HMG1 (High Mobility Group Box 1 protein) levels suggest a necrotic cell death. Notably, the cytotoxic effects were dependent on a direct contact of cells and BGs and could not be observed using indirect cultivation settings. Our data suggest that BGs might represent promising materials for the treatment of GCTB in order to reduce tumor recurrence with simultaneous enhancement of bone regeneration.

Calcaneal Bone Tumors.

Bone tumors of the foot are an uncommon finding. Most tumors are found incidentally on imaging and are benign. Care must be taken although due to the aggressive nature of malignant bone tumors that can occur in the calcaneus. Malignant lesions will more commonly present with symptoms of pain and swelling. Often misdiagnosed as soft tissue injuries, it is critical to be able to diagnose and treat these lesions early. Imaging plays an important role with plain films and advanced imaging. Surgical treatments can range from curettage with grafting to amputation for more aggressive lesions.

Novel Strategy of Curettage and Adjuvant Microwave Therapy for the Treatment of Giant Cell Tumor of Bone in Extremities: A Preliminary Study.

OBJECTIVES: To evaluate whether curettage with adjuvant microwave therapy was successful in the treatment of giant cell tumor of the bone (GCTB) in extremities, especially for GCTB with pathological fractures and GCTB of the distal radius. METHODS: This was a retrospective study of 54 cases of GCTB of the extremities treated by curettage with adjuvant microwave therapy between 2007 and 2019. Five patients were lost to follow up and excluded from the study. A total of 33 male and 21 female patients were included in this study. Patients were aged 15-57 years (mean 29.72 ± 10.48 years). Among these patients, there were 10 cases of GCTB with pathological fractures and eight cases of GCTB of the distal radius; one of these cases was combined with a pathological fracture. Comprehensive imaging examinations (X-rays [including lesion site and chest], CT, MRI, emission computed tomography, and pathology examination) of all patients were reviewed. The clinical staging of these patients were evaluated radiologically using the Campanacci classification system based on the extent of spread of the tumor. All patients underwent curettage with adjuvant microwave therapy. Clinical and imaging evaluations were performed in all cases to check for recurrence or metastasis. Lower limb and upper limber function were assessed using the Musculoskeletal Tumor Society score (MSTS), and wrist function was assessed according to the disabilities of the arm, shoulder and hand (DASH) score. Data on surgical-related complications were recorded. RESULTS: All cases were followed up for 24-126 months (mean 60.69 ± 29.61 months). There were 24 patients with a Campanacci grade of 3 and 30 with a Campanacci grade of 2. The 52 patients were continuously disease-free. The local recurrence rate was 3.70% (2 patients). One patient had recurrence in the proximal femur, and the other developed in soft tissue of the calf muscle. No recurrence occurred for GCTB of the distal radius. One recurrence occurred in a GCTB with pathological fractures. The intervals were 9 and 28 months, respectively. The cases of recurrence all had a Campanacci grade of 3 (8.33%). The median MSTS among the 54 patients was 27.67 ± 3.81. The mean wrist function DASH score was 8.30 ± 2.53. The mean MSTS was 28.67 ± 1.63 and 26.71 ± 5.49 for patients with GCTB of the distal radius and for those with pathological fractures, respectively. In comparing patients with and without pathological fractures, there was no significant difference in the MSTS functional score. Five patients had complications after the surgery. CONCLUSION: Curettage with adjuvant microwave ablation therapy provided favorable local control and satisfactory functional outcomes in the treatment of GCTB, especially for cases with pathological fractures and those with GCTB of the distal radius.

Giant Cell Tumour of Distal Left Tibia: A Case Report.

Giant cell tumours of bone are relatively uncommon, accounting for about 5% of all primary bone tumours. They are generally classified as benign bone tumours. However, some of them might be locally aggressive. The peak incidence is between second and fourth decades of life. They are commonly found at the epiphyseal and, occasionally, metaphyseal zones of long bones such as radius, femur and tibia. They most often present as painless swellings; however, pain may be experienced as a result of pressure on the surrounding soft tissues. The relevant diagnostic investigations that help in establishing the diagnosis include plain x-rays, Magnetic resonance imaging (MRI), CT and tissue biopsy for histological confirmation. Traditionally, surgery is the mainstay of treatment of the disease. Other modalities include radiation, tumour embolization and injectable drugs for surgically inaccessible or recurrent cases.

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

Giant cell tumour of the bone (GCTB) has been classically treated surgically. With the advent of denosumab, there is potential to use it as a targeted therapy to downstage the tumour and control its progression. Like all new therapies, the dosage, duration, and long-term effects of treatment can only be determined over the time through numerous trials and errors. The current recommendation of use of the monoclonal antibody is 3-4 months of neoadjuvant denosumab in patients with advanced GCTB for cases who were not candidates for primary curettage initially, and prolonged use for surgically unsalvageable GCTB. The use of Denosumab in the adjuvant setting to prevent recurrence is not established.

Exploring the Proteomic Alterations from Untreated and Cryoablation and Irradiation Treated Giant Cell Tumors of Bone Using Liquid-Chromatography Tandem Mass Spectrometry.

Giant cell tumors of bone (GCT) are benign tumors that show a locally aggressive nature and affect bones' architecture. Recently, cryoablation and irradiation treatments have shown promising results in GCT patients with faster recovery and less recurrence and metastasis. Therefore, it became a gold standard surgical treatment for patients. Hence, we have compared GCT-untreated, cryoablation, and irradiation-treated samples to identify protein alterations using high-frequency liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Our label-free quantification analysis revealed a total of 107 proteins (p < 0.01) with 26 up-regulated (< 2-folds to 5-fold), and 81 down-regulated (> 0.1 to 0.5 folds) proteins were identified from GCT-untreated and treated groups. Based on pathway analysis, most of the identified up-regulated proteins involved in critical metabolic functions associated with tumor proliferation, angiogenesis, and metastasis. On the other hand, the down-regulated proteins involved in glycolysis, tumor microenvironment, and apoptosis. The observed higher expressions of matrix metalloproteinase 9 (MMP9) and TGF-beta in the GCT-untreated group associated with bones' osteolytic process. Interestingly, both the proteins showed reduced expressions after cryoablation treatment, and contrast expressions identified in the irradiation treated group. Therefore, these expressions were confirmed by immunoblot analysis. In addition to these, several glycolytic enzymes, immune markers, extracellular matrix (ECM), and heat shock proteins showed adverse expressions in the GCT-untreated group were identified with favorable regulations after treatment. Therefore, the identified expression profiles will provide a better picture of treatment efficacy and effect on the molecular environment of GCT.

[Tumors affecting the temporomandibular joint - a literature review]. / Tumeurs de l'articulation temporomandibulaire ­ revue de la littérature.

Benign and malign tumors can affect the temporomandibular joint (TMJ) as any other articulation. Nevertheless, TMJ tumors are rare and mostly benign. Their clinical expression is varied including symptomatology similar to TMJ dysfunctional disorders, otologic or neurologic pathologies. In some cases, they remain totally asymptomatic. Hence, diagnosis is difficult since the symptomatology can be misleading with TMJ dysfunctional disorders or otologic disorders wrongly diagnosed. There is thus frequently a long delay between symptoms onset and diagnosis. The great variety of TMJ lesions explains the wide range of possible treatment modalities, mostly based on surgery. We provide here a review of the lesions originating from the TMJ. Tumoral or cystic mandibular lesion affecting the TMJ through local extension will not be discussed. Osteoma, osteoid osteoma, osteoblastoma, chondroma, osteochondroma, chondroblastoma, tenosynovial giant cell tumors, giant cell lesions, non-ossifying fibroma, hemangioma, lipoma or Langerhans cell histiocytosis are all possible diagnosis among the benign tumors found in the TMJ. Pseudotumors include synovial chondromatosis and aneurysmal bone cyst. Finally, malign tumors of the TMJ include mainly sarcomas (osteosarcoma, chondrosarcoma, synovial sarcoma, Ewing sarcoma, and fibrosarcoma), but also multiple myeloma and secondary metastases. We will review the clinical, radiological and histological aspects of each of these lesions. The treatment and the recurrence risk will also be discussed.

Incidence, Management, and Outcomes of Spinal Giant Cell Tumor of Bone in Adult Patients: A National Cancer Database Analysis.

OBJECTIVE: Giant cell tumors (GCTs) constitute 5% of all primary bone tumors with spinal GCTs (SGCTs) accounting for 2%-15% of all GCTs. The standard of care for SGCT has been maximal surgical resection. However, many adjuvant therapies have been used owing to the difficulty in achieving gross total resection combined with the high local recurrence rate. The purpose of the present study was to analyze the incidence, management, and outcomes of SGCT. METHODS: Patients with diagnosis codes specific for SGCT were queried from the National Cancer Database from 2004 to 2016. The outcomes were investigated using Cox univariate and multivariate regression analyses, and survival curves were generated for comparative visualization. RESULTS: The search criteria identified 92 patients in the NCDB dataset from 2004 to 2016 with a diagnosis of SGCT. Of the 92 patients, 64.1% had undergone surgical intervention, 24.8% had received radiotherapy, and 15.2% had received immunotherapy. Univariate analysis revealed that age ≥55 years and tumor location in the sacrum/coccyx were associated with worsened overall survival (OS) and that surgical resection was associated with improved OS. On multivariate analysis, age 55-64 years was associated with worsened OS, and radical surgical resection was associated with improved OS. The survival analysis revealed improved OS with surgery but not with radiotherapy, chemotherapy, or immunotherapy. CONCLUSION: SGCT is a rare primary bone tumor of the vertebral column. The standard of care has been surgical resection with the goal of gross total resection; however, adjuvant therapies have often been used. Our study found that surgical resection significantly improved OS and that immunotherapy neared significance in improving OS.

[Interpretation of 2020 NCCN Clinical Practice Guidelines in Oncology-Bone Cancer].

The specialty of bone cancer has developed rapidly in China in recent years, but because of the low incidence of these diseases and the unbalanced development of different regions, the malpractice problem of diagnosis and treatment is still outstanding.The NCCN clinical practice guide for bone cancer in the United States has been updated for several years and is now more mature and has been recognized worldwide.It can provide reference for medical professionals in related fields in China, it covers the most common bone tumors such as osteosarcoma, Ewing's sarcoma, chondrosarcoma, giant cell tumor of bone and chordoma.This article describes and interprets the core diagnostic and therapeutic contents of NCCN clinical practice guide for bone cancers.

Histomorphometric Analysis of Pre- and Post-Denosumab-Treated Giant Cell Tumor of Bone.

Context. Denosumab is a monoclonal antibody against RANK ligand. Its administration in giant cell tumor of bone (GCTB) cases results in elimination of giant cells and new bone formation. Neoplastic stromal cells of GCTB harbor mutation of histone 3.3 and have pre-osteoblastic properties and thus express SATB2. Objectives. To (1) analyze histological changes in post-denosumab-treated GCTB, (2) analyze expression of H3.3G34W and SATB2 in pre- and post-denosumab-treated samples, and (3) to discuss why changes occur in the expression of not only H3.3G34W but also SATB2. Materials and Methods. Hematoxylin and eosin slides of 19 cases of denosumab-treated GCTB were reviewed. Immunohistochemical stains H3.3G34W and SATB2 were performed. The number of positive mononuclear cells were counted and graded. Results. Complete absence of osteoclast-like giant cells (OCLGCs) was noted in most cases along with a fibro-osseous component merging with peripheral shell of reactive bone. Irregular trabeculae of woven bone and osteoid with focal osteoblastic rimming was seen. Spindle cells were arranged predominantly in fascicular pattern. Morphometric analysis of H3.3G34W showed a mean of 68.8% positive stromal cells in pretreatment and a mean of 26.9% positive stromal cells in posttreated specimens with a statistically significant P value (.001). Mean percentage of SATB2-positive stromal cells in the pre- and posttreatment specimens was 36.46% and 20.8%, respectively. Conclusions. Our study validates that denosumab treatment results in marked reduction of OCLGCs with increased osteoblastic activity. Decreased expression of H3.3G34W in posttreatment may be a result of decreased antigenicity of neoplastic mononuclear cells. No significant change in SATB2 expression was noted.

Is Treatment with Denosumab Associated with Local Recurrence in Patients with Giant Cell Tumor of Bone Treated with Curettage? A Systematic Review.

BACKGROUND: Denosumab, a monoclonal antibody that binds to receptor activation of nuclear factor-kappa ß ligand (RANKL), has been used as a drug to treat aggressive giant cell tumors of bone. It is unclear whether preoperative denosumab therapy is associated with the local recurrence risk in patients with giant cell tumors of bone treated with curettage. Early evidence suggests that denosumab treatment is associated with a reduction in local recurrence, but other studies have questioned that premise. Curettage after a short course of denosumab (3 to 4 months) has been recommended, especially for large, aggressive giant cell tumors in which complete curettage is difficult to achieve. No randomized studies have documented the benefit of this approach, and some investigators have reported higher local recurrence after denosumab treatment. Due to this confusion, we performed a systematic analysis of existing reports to attempt to answer this question and determine whether the appropriate preoperative denosumab therapy duration could be established. QUESTIONS/PURPOSES: (1) Is the use of preoperative denosumab associated with local recurrence risk in patients with giant cell tumors of bone treated with curettage compared with those treated with curettage alone? (2) Is the preoperative denosumab therapy duration associated with local recurrence after curettage? METHODS: We searched the PubMed, EMBASE, and CENTRAL databases on April 26, 2019 and included both randomized and non-randomized studies that compared local recurrence between patients who had giant cell tumors of bone and were treated with curettage after preoperative denosumab and patients treated with curettage alone. Two authors independently screened the studies. There were no randomized studies dealing with denosumab in giant cell tumors of bone, and generally, denosumab was used for more aggressive tumors. We assessed the quality of the included studies using the Risk of Bias Assessment tool for Non-randomized Studies, with a moderate overall risk of bias. We registered our protocol in PROSPERO (registration number CRD42019133288). We selected seven eligible studies involving 619 patients for the final analysis. RESULTS: The proportion of patients with local recurrence ranged from 20% to 100% in the curettage with preoperative denosumab group and ranged from 0% to 50% in the curettage-alone group. The odds ratio of local recurrence ranged from 1.07 to 37.80 in no more than 6 months of preoperative denosumab duration group and ranged from 0.60 to 28.33 in more than 6 months of preoperative denosumab duration group. CONCLUSIONS: The available evidence for the benefit of denosumab in more aggressive giant cell tumors is inconclusive, and denosumab treatment may even be associated with an increase in the proportion of patients experiencing local recurrence. Because there are no randomized studies and the existing studies are of poor quality due to indication bias (the most aggressive Campanacci 3 lesions or those where even a resection would be difficult and result in morbidity are generally the patients who are treated with denosumab), the evidence to suggest a disadvantage is weak. Denosumab treatment should be viewed with caution until more definitive, randomized studies documenting a benefit (or not) have been conducted. Furthermore, we could not find evidence to suggest an appropriate length of preoperative denosumab before curettage.

Preoperative Denosumab plus Surgery in the Management of Giant Cell Tumor of Bone: A Comprehensive Narrative Literature Review.

Giant cell tumor of bone (GCTB) is a biologically benign osteolytic tumor that affects the metaphyseal/epiphyseal portions of bones. Histologically, GCTB is composed of osteoclast-like multinucleated giant cells that express receptor activator of nuclear factor kappa B (RANK), and neoplastic mesenchymal stromal cells that express RANK ligand (RANKL). The pathogenesis of GCTB is primarily attributable to the RANK-RANKL interaction, resulting in the activation of osteoclasts and the resultant osteolytic phenotype. Denosumab is a monoclonal antibody targeted against RANKL. In 2013, it was approved by the United States Food and Drug Administration (FDA) for the treatment of adults and skeletally mature adolescents with GCTB that is inoperable, or initial surgery is expected to culminate in substantial morbidity. The aim of this study is to narratively review the current literature on the role of preoperative denosumab followed by surgery in the management of patients with GCTB. In brief, caution should be exercised in the interpretation of existing data on preoperative denosumab in the management of GCTB patients, owing to some critical limitations, for example, short follow-up and only a minority of patients have undergone intralesional surgery following denosumab therapy. All in all, administration of preoperative denosumab is associated with clinical, radiological, and histopathological therapeutic benefits. It is also associated with tolerability, safety, surgical downstaging and less morbid salvageable procedures. Preoperative denosumab does not seem to reduce the likelihood of local recurrence after intralesional therapy; a planned randomized phase III clinical trial (JCOG 1610) will holistically address this concern. Furthermore, more than ten cases of denosumab-related malignant transformation of GCTB have been reported in literature. Lastly, large-sized phase III randomized clinical trials with long-term follow-up data are warranted to withdraw concrete conclusions and recommendations.

A new computerized tomography classification to evaluate response to Denosumab in giant cell tumors in the extremities.

OBJECTIVES: The aim of this study was to describe the cohort of patients who have been treated with Denosumab as neoadjuvant therapy prior to surgery for aggressive giant cell tumor of bone in the extremities, to evaluate the radiological responses to Denosumab comparing Choi criteria and a newly described computerized tomography (CT) classification, and to evaluate the risk of local recurrence after intralesional curettage or radical excision. METHODS: We retrospectively evaluated 36 patients (20 females and 16 males; mean age at diagnosis 36 years (range, 18-64)) treated with neoadjuvant Denosumab therapy prior to surgery for aggressive giant cell tumor of bone in the extremities. The radiological responses to Denosumab treatment were analyzed on the preoperative images after the neoadjuvant course with the Choi criteria and with a newly proposed classification based on CT. All these images were independently reviewed by two of the researchers. Surgical intervention methods were noted and local recurrence rates were evaluated. The correlation between radiological response amount and local recurrence were analyzed for both Choi criteria and the new CT classification. RESULTS: Denosumab was administered for a mean of 21 weeks (range 7-133). Five patients also had a short postoperative course. According to Choi criteria there was a radiological response in 32 patients (89%), while the new CT classification identified responses in all the 36 patients (100%). The identification of changes after 7 weeks of treatment was higher using the CT classification compared to Choi criteria (p = 0.043 vs p = 0.462). The surgical interventions after Denosumab comprised curettage in 29 patients (74%) and resection in 7 (26%). Local recurrence was higher in patients managed with intralesional curettage than in those treated with en bloc resection (55.1% vs 0%, p < 0.001). At last follow up 19 patients (53%) required en bloc resections. Good responders to Denosumab (type 2C) had lower risk of local recurrence (p = 0.047) after either resection or curettage. CONCLUSION: The new CT classification evaluated more accurately the response to Denosumab. Our experience suggests that the requirement for radical bone resection remains high despite the use of Denosumab. LEVEL OF EVIDENCE: Level IV, Therapeutic Study.

Successful total en bloc spondylectomy of the L3 vertebra with a paravertebral giant cell tumor following preoperative treatment with denosumab: a case report.

BACKGROUND: Giant cell tumor is known to be a benign neoplasm that arises most commonly in the long bones, while cases in the spine are rare. Recently, denosumab, a monoclonal antibody that inhibits receptor activator of nuclear factor-kappa ß ligand, has been used to treat patients with giant cell tumor. However, there are few reports of total en bloc spondylectomy being used for paravertebral giant cell tumor lesions following denosumab therapy. CASE PRESENTATION: Our patient was a 20-year-old Japanese woman with a 4-month history of lower back pain. A spinal computed tomography scan and magnetic resonance imaging of her lumbar spine revealed an osteolytic lesion involving the L3 vertebral body, and the tumor extended toward the left side of the paravertebral soft tissue and into the left pedicle. The lesion was diagnosed as a giant cell tumor by needle biopsy. Denosumab treatment calcified the paravertebral giant cell tumor lesion and the tumor vertebral body was removed completely by total en bloc spondylectomy. CONCLUSION: This case report describes a patient with a paravertebral giant cell tumor who was successfully treated by preoperative denosumab injection followed by total en bloc spondylectomy.

Giant Cell Tumor of Bone: Review of Current Literature, Evaluation, and Treatment Options.

Giant cell tumor of bone is a benign albeit aggressive tumor commonly affecting the bones of the knee. Patients with these tumors present with pain, swelling, and inability to bear weight on the involved extremity. These destructive tumors typically arise in the metaphyseal region of the long bones in individuals in the second, third, and fourth generations of life. Histologically, the multinucleated giant cells are the hallmark of the lesion, easily recognized on histological review, which recently have become therapeutic targets for medical management of the disease. For decades, surgical management has been the primary treatment for giant cell tumor of the bone. Some tumors can be treated with excision and filling of the osseous void with bone cement or allograft. This is an effective treatment option with a low to moderate risk of local recurrence while preserving limb function. For more destructive tumors, wide excision and reconstruction with prosthetic, structural allograft or combined allograft prosthetic components are utilized. Advances in medical management of the disease have also demonstrated promise as an effective treatment; however, its use has usually been limited to the treatment of metastatic disease, recurrent disease or when advanced local disease would require surgical treatment felt to be overly morbid.