Giant Cell Tumor of Bone
Conditions
Keywords
Giant cell tumor of bone, Denousmab, Pathologic, Clinical, Mechansim
Brief summary
Giant cell tumor of bone (GCTb) is a primary, osteolytic, benign tumor of the bone. Surgery is the commonly used treatment. Discovery of RANKL and its human monoclonal antibody, denosumab, led to use of denosumab for treatment of GCT. The aim of this study was to evaluate clinical and pathological results of treatment of relapsed or refractoriness GCT with denosumab and to assess adverse effect profile and recurrence rate.
Detailed description
Giant cell tumor of bone (GCTb) is an aggressive, benign bone tumor. GCTb, which was first defined by Cooper and Travers, can produce pulmonary metastasis, albeit rarely (1-6%). GCTb constitutes 5% of primary bone tumors and 20% of benign bone tumors. Histologically, the tumour consists of a proliferation of mononuclear cells, accompanied by a population of non-neoplastic osteoclast-like giant cells and mononuclear osteoclast precursors. Currently, it is thought that proliferating neoplastic cells produce a number of cytokines and mediators, including the receptor activator of nuclear factor κ-B-ligand (RANK-RANKL) system, that recruit osteoclast precursors and induce their maturation into multinucleated osteoclast. The standard management of GCTb is based on surgery with several local adjuvant treatments like methacrylate cement, phenol or cryotherapy to reduce the risk of recurrence, while bisphosphonates are used in some cases to decrease bone resorption and for pain relief in inoperable tumours or metastatic disease. In the last 5 years the use of denosumab, a fully human monoclonal antibody already licensed for postmenopausal osteoporosis and prevention of skeletal related events in bone metastases from solid tumours, has been introduced in the treatment strategy of GCTb. In this study we examined the clinical, radiological, histological and underlying mechanism features of a series of GCTb, before and after denosumab administration, comparing baseline and resection specimens. Moreover, we examined the safety of the drug and on the angiogenesis through the determination of microvascular density (MVD).
Interventions
DRUGDenosumab
Denosumab (trade names Prolia and Xgeva) is a human monoclonal antibody for the treatment of osteoporosis, treatment-induced bone loss, metastases to bone, and giant cell tumor of bone.Denosumab is a RANKL inhibitor, which works by preventing the development of osteoclasts which are cells that break down bone.
Sponsors
Hebei Medical University Third Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Giant cell tumor of bone patients confirmed by clinical, medical imaging and Pathology.
Exclusion criteria
* (1) less than 14 patients; 2) pregnant patients; 3) A patient who receives other medications during treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Molecular analysis (RT-PCR for RANKL, RANK, OPG,Col-I, VEGF) | 6 month | Tissures mRNA was extracted using TRIzol reagent (Invitrogen, Carlsbad, CA). The RNA concentration and quality were assessed using a Quawell Q5000 spectrophotometer (Quawell, San Jose, CA). Reverse transcription PCR was performed using a Gene Amp 7700 Sequence Detection System (Applied Biosystems, Foster City, CA) and custom-designed, validated primers for Col1α1, Col2α1, Aggrecan, MMP-13, and ADAMTS-4. GAPDH was used as the housekeeping gene. Relative gene expression changes were reported using the 2(-Delta Delta C(T)) method as previously described. The experiment was repeated in triplicate to ensure accuracy. |
| Molecular analysis (Immunohistochemistry for RANKL, RANK, OPG,Col-I, VEGF) | 6 month | For collagen RANKL (Receptor Activator for Nuclear Factor-κ B Ligand), RANK (Receptor Activator for Nuclear Factor-κ B), OPG (Osteoprotegerin), Col-I (type I Collagen), VEGF (Vascular Endothelial Growth Factor) immunohistochemistry, sections were deparaffinized, rehydrated, and immunostained with a SA1024 SABC-POD kit and Kit-0017 DAB detection kit. Briefly, antigen retrieval was performed, and endogenous peroxidases were then inactivated prior to incubation with primary antibodies overnight at 4°C. This was followed by incubation with a biotinylated secondary antibody and a streptavidin-biotin complex peroxidase solution. Diaminobenzidine (DAB) chromogen was applied and counterstained with hematoxylin for antibody detection. Images were captured by a microscope system at 400-magnification. The integrated optical density values of each factor were semiquantitatively analyzed using Imaging Pro Plus 6.0 software. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hematology test - Tartrate Resistant Acid Phosphatase | 6 months | Tartrate-resistant acid phosphatase, a bone resorption marker, is secreted from osteoclasts and this marker is reported to be high in patients with giant cell tumor of bone. We investigated the effects of denosumab and the usefulness of a tartrate-resistant acid phosphatase as a monitoring marker in the management of a refractory giant cell tumor of bone. Tartrate-resistant acid phosphatase secretion was measured in the patient's serum to monitor the response to denosumab, and a rapid normalization of the marker was observed after the first denosumab administration. |
| Follow-up for recrudescence | 6 month to 1 year | Patients were followed up regularly for local or systemic tumor recurrence by X-ray, CT, MRI, ECT. The follow-up period was 3 months. |
| Micro-vessel density or area by IHC - stained slides | 6 month | IHC - stained for VEGF images were used for microvessel density (MVD) and vascular bud relative area analysis. MVD was measured by counting the number of cartilage endplate vascular buds (an average of cephalic and caudal vascular buds). The ratio of vascular bud area to the total endplate area was measured for vascular bud relative area analysis using the grid method. MVD and vascular bud relative area analyses were repeated at least three times for enhanced accuracy |
| Imaging changes by X-ray, CT, MRI, ECT. | 6 month | The patients' clinical information, images from radiographs, CT and MRI before and after Denosumab-treatment were recorded and analyzed. Tumor volume was measured on coronal, transverse, and sagital MRI or CT scansof the lesion; and maximum height, width, and depth were recorded; and the volume was calculated using the formula of an ellopsoid mass volume = \[(π/6) × height × width × depth\]. If CT or MRI were not available, tumor volume was measured on two-plane radiograghs. |
| Morphological change - HE (Hematoxylin-Eosin) staining | 6 month | For histological analysis of the adjacent intervertebral disc and fusion mass, the tissures of the Giant cell tumor of bone were fixed in 10% neutral buffered formalin, decalcified in 10% EDTA-2Na for 3 months, and then embedded in paraffin. They were subsequently cut into 5-mm sections with cationic slides. Slides of the tissures of the Giant cell tumor of bone were stained with H&E and captured by a microscope system (BX53; Olympus, Tokyo, Japan). |
| Visual Analog Score - Pain evaluation | 6 months | Visual analog scale \[VAS\] is a measure of pain intensity. It is a continuous scale comprised of a horizontal (called horizontal visual analogue scale) or,vertical called vertical visual analog scale usually 10 cm or 100 mm length \[both the gradations are used\]. It is anchored by two verbal descriptors, one for each symptom extreme. For pain intensity, the scale is most commonly anchored by no pain (score of 0) and pain as bad as it could be or worst imaginable pain (score of 100 \[on 100-mm scale\] |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | 3 year | The CTCAE v.4 criteria was used to evaluate late toxicity for all patients. Toxicity scores were recalculated for patients treated before publication of CTCAE v4.0 scale. |
Countries
China
Contacts
Backup ContactGuochuan Zhang, M.D.
Primary ContactZhuang Zhou, Ph.D
Outcome results
None listed