PURPOSE: Denosumab, a new monoclonal antibody that inhibits receptor activator for nuclear factor Kβ ligand (RANKL), has recently been approved by FDA for the treatment of aggressive giant cell tumor of bone (GCTB). So we initiated this study to evaluate the clinical benifits of denosumab used preoperatively or postoperatively. METHODS: Patients diagnosed with classic sacral GCT without metastasis were included in this study. Patients were assigned into 3 groups according to the use of denosumab: control group 1, post-operative group 2 and neoadjuvant group 3. The latter two groups were treated with 120 mg of subcutaneous denosumab every 4 weeks with loading doses on days 8 and 15 of the first cycle. The primary endpoints were event-free-survival (EFS) and objective response rate (OPR) based on RECIST criteria. A system (MUD system) proposed by our center was applied to score the sacral nerve deficit changes before surgery in group 3. RESULTS: A total 30 patients (13 men and 17 women, mean age 34.7 years, range 15-56) were enrolled from April 2014 to July 2016. Group 1 included 10 patients, group 2 9 and group 3 11. The study ended in March 01, 2017, and followup ranged from 3 to 36 months (mean 18.3). Two patients with PET-CT showed SUV max uptake down to muscle tissue level. In the neoadjuvant group 3 7 patients had partial responses and 4 stable disease (ORR 63.6%; 95% CI 35-92). Most (80%) patients achieved significant improvement in pain and great relief in the bladder and bowel functions. In 4 patients the urocatheter was removed after neoadjuvant denosumab. CONCLUSION: Neoadjuvant therapy with denosumab can significantly relieve the symptoms and neurologic deficits.
PURPOSE:Denosumab, a new monoclonal antibody that inhibits receptor activator for nuclear factor Kβ ligand (RANKL), has recently been approved by FDA for the treatment of aggressive giant cell tumor of bone (GCTB). So we initiated this study to evaluate the clinical benifits of denosumab used preoperatively or postoperatively. METHODS:Patients diagnosed with classic sacral GCT without metastasis were included in this study. Patients were assigned into 3 groups according to the use of denosumab: control group 1, post-operative group 2 and neoadjuvant group 3. The latter two groups were treated with 120 mg of subcutaneous denosumab every 4 weeks with loading doses on days 8 and 15 of the first cycle. The primary endpoints were event-free-survival (EFS) and objective response rate (OPR) based on RECIST criteria. A system (MUD system) proposed by our center was applied to score the sacral nerve deficit changes before surgery in group 3. RESULTS: A total 30 patients (13 men and 17 women, mean age 34.7 years, range 15-56) were enrolled from April 2014 to July 2016. Group 1 included 10 patients, group 2 9 and group 3 11. The study ended in March 01, 2017, and followup ranged from 3 to 36 months (mean 18.3). Two patients with PET-CT showed SUV max uptake down to muscle tissue level. In the neoadjuvant group 3 7 patients had partial responses and 4 stable disease (ORR 63.6%; 95% CI 35-92). Most (80%) patients achieved significant improvement in pain and great relief in the bladder and bowel functions. In 4 patients the urocatheter was removed after neoadjuvant denosumab. CONCLUSION: Neoadjuvant therapy with denosumab can significantly relieve the symptoms and neurologic deficits.