Giant cell tumor of bone: Effect of longer dosing intervals of denosumab on tumor control and bone related complications.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11525-11525
Author(s):  
Cindy Jiang ◽  
Lili Zhao ◽  
Scott Schuetze ◽  
Rashmi Chugh
Keyword(s):  
Giant Cell Tumor ◽  
Giant Cell ◽  
Cell Tumor ◽  
Tumor Control ◽  
Free Text ◽  
Dosing Interval ◽  
Increased Risk ◽  
Significant Difference ◽  
Dosing Intervals ◽  
Bone Complications

11525 Background: Giant cell tumor of bone (GCTB) is a benign but locally aggressive bone neoplasm characterized by osteoclast activation causing destructive osteolysis. Denosumab, a human monoclonal antibody against RANK ligand, has emerged as an effective treatment option when surgery is not recommended, but can cause significant bone toxicity. Current standard dosing is every 4 weeks after 3 weekly loading doses. As patients (pts) with GCTB are often young adults, frequent denosumab administration long-term may be burdensome and associated with increased risk of complications. We assessed whether alternative, longer dosing intervals are associated with differences in efficacy or bone toxicity. Methods: Retrospective chart review was conducted on GCTB pts over 18 years old at University of Michigan who received at least 1 year of standard denosumab treatment. Pts were identified using a free-text medical record search engine with keywords “giant cell tumor” and “denosumab” until August 2020. We compared bone-related adverse effects and tumor control in pts who continued denosumab every 4 weeks versus longer treatment intervals. Decision to increase interval between doses was based on provider and pt discussion and preference as part of routine medical care. Results: 37 GCTB pts were identified; 51% female and 49% male. Average age was 41 years (range 22-73). Most common primary location was lower extremity (38%), followed by pelvis (35%), upper extremity (14%), spine (8%), and head/neck (5%). Metastasis were present at start of treatment in 14% of pts, involving lung (n = 4) and spine (n = 1). Pts received median of 71 (range 15-139) total doses of denosumab. Dosing interval was increased in 38% (n = 14). With the first interval change, 43% changed to every 6 weeks, 29% every 8 weeks, and 29% every 12 weeks dosing. Most common final dosing interval was 12 weeks (n = 8). 6 pts (16%) had bone complications after mean of 56 doses. This included osteonecrosis of the jaw (n = 4), atypical fracture (n = 1), and non-healing dental wounds (n = 2). All pts with bone complications were treated on the monthly dosing schedule, but there was no statistically significant difference compared to longer intervals (p = 0.22). Pts with GCT progression (n = 10) were either no longer receiving therapy or had missed denosumab doses. There was no statistically significant difference in PFS with standard vs. interval increased dosing (p = 0.97). However, 5-year PFS was superior with interval increased vs standard dosing (p = 0.036). Conclusions: Increasing the interval of denosumab dosing for GCTB provided similar tumor control as compared to standard dosing and is potentially associated with less bone toxicity and more convenience for afflicted pts. Further larger scale studies are needed to better define the optimal interval of denosumab administration in GCTB and the effect on efficacy, toxicity, and associated health care expense.

scholarly journals Anti-IL17 antibody Secukinumab therapy is associated with ossification in giant cell tumor of bone: a case report of pathologic similarities and therapeutic potential similar to Denosumab

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Andrew Chandler ◽  
Meredith K. Bartelstein ◽  
Tomohiro Fujiwara ◽  
Cristina R. Antonescu ◽  
John H. Healey ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Giant Cell Tumor ◽  
Giant Cell ◽  
Therapeutic Potential ◽  
Quantitative Polymerase Chain Reaction ◽  
Treatment Method ◽  
Giant Cells ◽  
Cell Tumor ◽  
Pcr Analysis ◽  
Increased Risk

Abstract Background Giant cell tumor of bone is a benign, locally aggressive neoplasm. Surgical resection is the preferred treatment method. However, for cases in which resection poses an increased risk to the patient, denosumab (anti-RANKL monoclonal antibody) is considered. Secukinumab is an anti-IL-17 antibody that is used in psoriatic arthritis to reduce bone resorption and articular damage. Case presentation One case of giant cell tumor of bone (GCTB) in a patient treated with secukinumab for psoriatic arthritis demonstrated findings significant for intra-lesional calcifications. Histologic examination showed ossification, new bone formation, and remodeling. A paucity of osteoclast type giant cells was noted. Real-time quantitative polymerase-chain-reaction (qRT-PCR) analysis revealed decreased osteoclast function compared to treatment-naive GCTB. Conclusions Secukinumab may play a role in bone remodeling for GCTB. Radiologists, surgeons, and pathologists should be aware of this interaction, which can cause lesional ossification. Further research is required to define the therapeutic potential of this drug for GCTB and osteolytic disease.

scholarly journals Dosing interval adjustment of denosumab for the treatment of giant cell tumor of the sphenoid bone: A case report

2020 ◽  
Vol 11 ◽  
pp. 370
Author(s):  
Motoki Tanikawa ◽  
Hiroshi Yamada ◽  
Tomohiro Sakata ◽  
Mitsuhito Mase
Keyword(s):  
Giant Cell Tumor ◽  
Giant Cell ◽  
Cell Tumor ◽  
Sphenoid Bone ◽  
Current Case ◽  
Endoscopic Endonasal ◽  
Subcutaneous Injections ◽  
Dosing Interval ◽  
Monthly Dosing ◽  
Denosumab Treatment

Background: In the treatment of giant cell tumor of bone (GCTB), the efficacy and safety of denosumab, a receptor activator nuclear factor κ-B ligand inhibitor, has previously been demonstrated, especially for unresectable tumors. One of the current issues in denosumab treatment for unresectable GCTB is whether it can be discontinued, or whether the dosage or the dosing interval can safely be adjusted, if discontinuation is not possible, to avoid the occurrence of side effects. Case Description: A 15-year-old boy with diplopia was referred to our hospital after a space-occupying lesion in the sphenoid bone was found on head CT. Partial removal of the tumor was performed through an endoscopic endonasal approach, and pathological diagnosis was confirmed as GCTB. Thereafter, the patient received 120 mg subcutaneous injections of denosumab every 28 days for the first 2 years. Since bone formation was induced and sustained along with tumor reduction, the dosing interval was gradually extended, with 4 monthly dosing for the next 1 year, followed by 6 monthly dosing for the succeeding 2 years. With the extension of the dosing interval, the ossified tumor has regrown slightly, but within an acceptable range. Conclusion: Discontinuation of denosumab treatment for unresectable GCTB was not thought to be possible for the current case due to the nature of the drug, as reported in the literature. Extending the dosing interval up to 6 monthly, as could be done safely in the current case, can be considered a useful and appropriate measure.

scholarly journals Pre-operative denosumab is associated with higher risk of local recurrence in giant cell tumor of bone: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Xi Chen ◽  
Hairui Li ◽  
Shibai Zhu ◽  
Yiou Wang ◽  
Wenwei Qian
Keyword(s):  
Local Recurrence ◽  
Giant Cell Tumor ◽  
Giant Cell ◽  
Meta Analysis ◽  
Cell Tumor ◽  
Cochrane Library ◽  
Control Group ◽  
Risk Of Recurrence ◽  
Increased Risk ◽  
The Cochrane Library

Abstract Background: In 2013, denosumab was introduced as peri-operative adjuvant treatment for giant cell tumor (GCT) of bone as it inhibits osteoclast activity. It is suggested that denosumab relives pain, facilitate curettage in lesions requiring resection initially. However, controversy remains whether denosumab increases the risk of local recurrence after surgery. Methods: Medline, Embase and the Cochrane Library were comprehensively searched in June 2019 to identify studies investigating the clinical outcome of GCT of bone with and without peri-operative denosumab after surgery. Data were gathered and a meta-analysis was conducted. Result: Ten studies with 1082 cases (169 in denosumab group, 913 in control group) were included. Overall, denosumab was associated with significantly higher risk of recurrence(P<0.02) and inferior 5 year recurrence free survival(P=0.000). Denosumab and curettage has a relatively higher risk of recurrence comparing to curettage alone(P=0.07). The risk of recurrence is not significantly increased if denosumab was administered both preoperatively and postoperatively(P=0.24). Conclusion: Administration of denosumab is associated with increased risk of recurrence due to a variety of reasons, though it is proven effective in relieving pain, enabling curettage and improved functional outcome. Post-operative denosumab is recommended as it continuously suppress/eliminate residue tumor cells.

scholarly journals Pre-operative denosumab is associated with higher risk of local recurrence in giant cell tumor of bone: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Xi Chen ◽  
Hairui Li ◽  
Shibai Zhu ◽  
Yiou Wang ◽  
Wenwei Qian
Keyword(s):  
Local Recurrence ◽  
Giant Cell Tumor ◽  
Giant Cell ◽  
Meta Analysis ◽  
Cell Tumor ◽  
Cochrane Library ◽  
Control Group ◽  
Risk Of Recurrence ◽  
Increased Risk ◽  
The Cochrane Library

Abstract Background In 2013, denosumab was introduced as peri-operative adjuvant treatment for giant cell tumor (GCT) of bone as it inhibits osteoclast activity. It is suggested that denosumab relives pain, facilitate curettage in lesions requiring resection initially. However, controversy remains whether denosumab increases the risk of local recurrence after surgery. Methods Medline, Embase and the Cochrane Library were comprehensively searched in June 2019 to identify studies investigating the clinical outcome of GCT of bone with and without peri-operative denosumab after surgery. Data were gathered and a meta-analysis was conducted. Result Ten studies with 1082 cases (169 in denosumab group, 913 in control group) were included. Overall, denosumab was associated with significantly higher risk of recurrence(P<0.02) and inferior 5 year recurrence free survival(P=0.000). Denosumab and curettage has a relatively higher risk of recurrence comparing to curettage alone(P=0.07). The risk of recurrence is not significantly increased if denosumab was administered both preoperatively and postoperatively(P=0.24). Conclusion Administration of denosumab is associated with increased risk of recurrence due to a variety of reasons, though it is proven effective in relieving pain, enabling curettage and improved functional outcome. Post-operative denosumab is recommended as it continuously suppress/eliminate residue tumor cells.

scholarly journals Pre-operative denosumab is associated with higher risk of local recurrence in giant cell tumor of bone: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Xi Chen ◽  
Hairui Li ◽  
Shibai Zhu ◽  
Yiou Wang ◽  
Wenwei Qian
Keyword(s):  
Local Recurrence ◽  
Giant Cell Tumor ◽  
Giant Cell ◽  
Meta Analysis ◽  
Cell Tumor ◽  
Cochrane Library ◽  
Control Group ◽  
Risk Of Recurrence ◽  
Increased Risk ◽  
The Cochrane Library

Abstract Background In 2013, denosumab was introduced as peri-operative adjuvant treatment for giant cell tumor (GCT) of bone as it inhibits osteoclast activity. It is suggested that denosumab relives pain, facilitate curettage in lesions requiring resection initially. However, controversy remains whether denosumab increases the risk of local recurrence after surgery. Methods Medline, Embase and the Cochrane Library were comprehensively searched in June 2019 to identify studies investigating the clinical outcome of GCT of bone with and without peri-operative denosumab after surgery. Data were gathered and a meta-analysis was conducted. Result Ten studies with 1082 cases (169 in denosumab group, 913 in control group) were included. Overall, denosumab was associated with significantly higher risk of recurrence(P<0.02) and inferior 5 year recurrence free survival(P=0.000). Denosumab and curettage has a relatively higher risk of recurrence comparing to curettage alone(P=0.07). The risk of recurrence is not significantly increased if denosumab was administered both preoperatively and postoperatively(P=0.24). Conclusion Administration of denosumab is associated with increased risk of recurrence due to a variety of reasons, though it is proven effective in relieving pain, enabling curettage and improved functional outcome. Post-operative denosumab is recommended as it continuously suppress/eliminate residue tumor cells.

scholarly journals Conservative surgery in the treatment of giant cell tumor of the sacrum: 35 years’ experience

2016 ◽  
Vol 24 (2) ◽  
pp. 228-240 ◽  
Author(s):  
Stepan V. Domovitov ◽  
Chandhanarat Chandhanayingyong ◽  
Patrick J. Boland ◽  
David G. McKeown ◽  
John H. Healey
Keyword(s):  
Giant Cell Tumor ◽  
Giant Cell ◽  
Disease Free Survival ◽  
Conservative Surgery ◽  
Cell Tumor ◽  
Bladder Function ◽  
Cancer Center ◽  
Tumor Control ◽  
Local Recurrences

OBJECT There is no consensus regarding the appropriate treatment of sacral giant cell tumor (GCT). There are 3 main management problems: tumor control, neurological loss, and pelvic instability. The objective of this study was to examine oncological, neurological, and structural outcomes of sacral GCT after intralesional excision and local intraoperative adjunctive treatment. METHODS The authors retrospectively reviewed the records of 24 patients with sacral GCT who underwent conservative surgery (intralesional resection/curettage) at Memorial Sloan Kettering Cancer Center from 1973 through 2012. They analyzed patient demographic data, tumor characteristics, and operative techniques, and examined possible correlations with postoperative functional outcomes, complications, recurrence, and mortality. RESULTS There were 7 local recurrences (30%) and 3 distant recurrences (13%). Three of 24 patients (12.5%) had significant neurological loss after treatment—specifically, severe bowel and/or bladder dysfunction, but all regained function within 1–4 years. Larger tumor size (> 320 cm3) was associated with greater postoperative neurological loss. Radiation therapy and preoperative embolization were associated with prolonged disease-free survival. There were no local recurrences among the 11 patients who were treated with both modalities. Based on radiographic and clinical assessment, spinopelvic stability was present in 23 of 24 patients at final follow-up. CONCLUSIONS High local and distant recurrence rates associated with sacral GCT suggest the need for careful local and systemic follow-up in managing these patients. Intraoperative preservation of sacral roots was associated with better pain relief, improvement in ambulatory function, and retention of bowel/bladder function in most patients. Fusion and instrumentation of the sacroiliac joint successfully achieved spinopelvic stability in cases deemed clinically unstable. Despite improvement in the management of sacral GCT over 35 years, a need for novel therapies remains. The strategy of combining radiotherapy and embolization merits further study.

scholarly journals Reconstruction and Repairment With Mini-plate and Bone Graft for HIV Positive Patients of Giant Cell Tumor of Long Bone: Retrospective Analysis of a Single-center Experience

2021 ◽  
Author(s):  
Biao Xu ◽  
Rui Ma ◽  
Qiang Zhang ◽  
Chang-song Zhao ◽  
Wen-sheng Zhang ◽  
...  
Keyword(s):  
Bone Graft ◽  
Giant Cell Tumor ◽  
Giant Cell ◽  
Proximal Tibia ◽  
Cell Tumor ◽  
Long Bone ◽  
Hiv Positive ◽  
Joint Function ◽  
Significant Difference ◽  
Mini Plate

Abstract Background: To evaluate the effect of reconstruction and repairment with mini-plate and bone graft for HIV positive patients of giant cell tumor of long bone.Methods: This research retrospectively analyzed 12 HIV positive patients with giant cell tumor of long bone, 11 male and 1 female, with a age range 16 to 68 years old (43.5 years old on average) were included. There were 5 cases of proximal tibia，3 cases of distal femur, 2 case of distal tibia, and 2 case of talus. From June 2012 to August 2020, curettage by ultrasonic scalpel were performed in all patients, combined with min- plate and bone graft treatment. All patients were followed up for 18-60 months. Limb function was evaluated by MSTS93 scoring system, and postoperative recurrence and distant metastasis, complications, MSTS93 score and fracture prognosis were observed.Results: No local recurrence and pulmonary metastases was observed. After surgery, all the 12 patients showed good bone morphologic repair and reconstruction, good bone healing , good joint function, and no pathological fracture around the lesion. One case of giant cell tumor of proximal tibia showed mild articular surface collapse, and mild valgus deformity of knee joint, but good joint function. The MSTS93 score of the patients 6 months after the operation was 24-27 points (24.5±1.08), with a significant difference (P < 0.05).Conclusion: Reconstruction and repairment with mini-plate and bone graft for HIV positive patients of giant cell tumor of long bone has achieved satisfactory results. The mini- plate takes up little space and is flexible for reconstruction and fixation, significantly reducing complications such as surgical site infection, preserving joint function and avoiding amputation. It is a safe and effective treatment method.

scholarly journals Reconstruction and Repairment with Mini- Plate and Bone Graft for HIV Positive Patients of Giant Cell Tumor of Long Bone: Retrospective Analysis of A Single-Center Experience

2021 ◽  
Author(s):  
Biao Xu ◽  
Rui Ma ◽  
Jie Wang ◽  
Qiang Zhang ◽  
Changsong Zhao ◽  
...  
Keyword(s):  
Bone Graft ◽  
Giant Cell Tumor ◽  
Giant Cell ◽  
Proximal Tibia ◽  
Cell Tumor ◽  
Long Bone ◽  
Hiv Positive ◽  
Joint Function ◽  
Significant Difference ◽  
Mini Plate

Abstract Background To evaluate the effect of reconstruction and repairment with mini- plate and bone graft for HIV positive patients of giant cell tumor of long bone. Methods This research retrospectively analyzed 12 HIV positive patients with giant cell tumor of long bone, 11 male and 1 female, with a age range 16 to 68 years old (43.5 years old on average) were included. There were 5 cases of proximal tibia,3 cases of distal femur, 2 case of distal tibia, and 2 case of talus. From June 2012 to August 2020, curettage by ultrasonic scalpel were performed in all patients, combined with min- plate and bone graft treatment. All patients were followed up for 18–60 months. Limb function was evaluated by MSTS93 scoring system, and postoperative recurrence and distant metastasis, complications, MSTS93 score and fracture prognosis were observed. Results No local recurrence and pulmonary metastases was observed. After surgery, all the 12 patients showed good bone morphologic repair and reconstruction, good bone healing, good joint function, and no pathological fracture around the lesion. One case of giant cell tumor of proximal tibia showed mild articular surface collapse, and mild valgus deformity of knee joint, but good joint function. The MSTS93 score of the patients 6 months after the operation was 24–27 points (24.5 ± 1.08), with a significant difference (P < 0.05). Conclusion Reconstruction and repairment with mini- plate and bone graft for HIV positive patients of giant cell tumor of long bone has achieved satisfactory results. The mini- plate takes up little space and is flexible for reconstruction and fixation, significantly reducing complications such as surgical site infection, preserving joint function and avoiding amputation. It is a safe and effective treatment method.

scholarly journals Giant cell tumor of the sacrum

2003 ◽  
Vol 15 (2) ◽  
pp. 1-4 ◽  
Author(s):  
R. Lor Randall
Keyword(s):  
Giant Cell Tumor ◽  
Giant Cell ◽  
Local Tumor Control ◽  
Cell Tumor ◽  
Lower Limbs ◽  
Tumor Control ◽  
Lower Back ◽  
Valuable Procedure ◽  
Sacral Resection ◽  
Bladder Symptoms

Giant cell tumor (GCT) is a locally highly aggressive tumor of bone comprising 5 to 10% of all benign bone tumors. The sacrum is the third most common site of involvement. Patients with sacral GCTs present with localized pain in the lower back that may radiate to one or both lower limbs. Vague abdominal complaints and bowel and bladder symptoms may also be present. Neuroimaging workup should include advanced modalities, preferably magnetic resonance imaging, prior to obtaining a biopsy specimen. Giant cell tumor has a 1 to 5% rate of metastasizing to the lung and may convert to a fulminate malignant variant, which has a very poor prognosis. The standard treatment for GCT is curettage combined with adjuvant bone grafting or cement-augmented stabilization. In appropriately selected cases, sacral resection is a valuable procedure to effect local tumor control and overall survival. Embolization may also prove palliative and/or curative in cases in which the tumor is unresectable or refractory to treatment.

scholarly journals Comparison of Denosumab and Zoledronic acid as neoadjuvant therapy in patients with giant cell tumor of bone

2021 ◽  
Vol 29 (2) ◽  
pp. 230949902110075
Author(s):  
Himanshu Kanwat ◽  
Roshan Banjara ◽  
Venkatesan Sampath Kumar ◽  
Abdul Majeed ◽  
Shivanand Gamnagatti ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Giant Cell Tumor ◽  
Giant Cell ◽  
Clinical Outcomes ◽  
Surgical Intervention ◽  
Cell Tumor ◽  
Adjuvant Setting ◽  
Treatment Rate ◽  
Recurrence Rates ◽  
Significant Difference

Objectives: Both Zoledronic acid and denosumab have been utilized in neo-adjuvant setting for facilitating surgery and downsizing the lesion in Giant cell tumor (GCT). This study is aimed at comparing Zoledronic acid and Denosumab, when used in neo-adjuvant setting, in terms of radiological and clinical outcomes in GCT undergoing surgical intervention. Patients and Methods: Patients undergoing surgical intervention for GCT who received either denosumab or Zoledronic acid as neoadjuvant agents were retrospectively analyzed for reduction in tumor load radiologically, change in surgical plan after therapy, facilitation of surgery, therapy related complications, cost of treatment, rate of local recurrence and clinical outcomes. Results: Twenty patients received denosumab and 19 patients received Zoledronic acid as neoadjuvant agent. There was no significant difference in radiological outcomes, facilitation of surgery and clinical outcomes at end of follow-up. Zoledronic acid group had lower number of recurrences, however, not statistically significant. Therapy with Zoledronic acid was significantly cheaper (p = 0.001). Conclusion: Zoledronic acid is a cheaper alternative to denosumab in terms of solidification of lesion, reducing recurrence rates and improving clinical outcomes. Larger prospective studies required to further delineate this outcome with Zoledronic acid.

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