ABSTRACT
Objective Parkinson's disease (PD) is a common degenerative disease of the central nervous system.The main pathological feature is the reduction of dopaminergic neurons,which induces motion symptoms such as resting tremor,muscle rigidity,bradykinesia,and postural disorder.The etiology and pathogenesis of PD are complex and related to a variety of factors.The current pathogenesis is related to mitochondrial dysfunction,oxidative stress,neuroinflammatory response,apoptosis,and autophagy.The early onset of PD is occult and the rate of misdiagnosis is high.It requires a new simple,safe,and effective early diagnosis method.The current methods of early diagnosis mainly include clinical non-motor symptoms,biomarkers,and imaging examination methods.
ABSTRACT
Objective To evaluate the safety and efficacy of denosumab in treatment of patients with pelvic giant cell tumor of bone (GCTB) during perioperative period. Methods This is a retrospective observational study. Twenty-three patients diagnosed with pelvic GCTB undergoing perioperative denosumab treatment in Musculoskeletal Tumor Center of Peking University People's Hospital from January 2014 to December 2016 were reviewed. The subjective adverse reactions and mandibular X-ray films were used to assess the drug safety. As for efficacy, imaging findings (including X-ray, CT, magnetic resonance imaging) were reviewed. MSTS-93 scoring system was applied in the postoperative functional assessment. Histological response rate, objective response rate, clinical benefit rate and event-free survival rate were all used to deficit the efficacy of denosumab in the treatment of pelvic GCTB combined with surgery. All the results of postoperative were compared statistically with pelvic GCTB patients who underwent surgery in the same hospital from 1999 to 2009. Results All the patients were firstly diagnosed as classic GCTB except for one case which was malignant pelvic GCTB. All patients received denosumab preoperatively and/or postoperatively, and the average number of medications was 8.43. According to the surgical patterns, patients were divided into intralesional surgery group (13 cases) and wide resection group (10 cases). The follow-up was 5-47 months(mean:27.30 months),recurrence was observed in 2 cases in the intralesional surgery group, none in the wide resection group. After drug administration, 13 cases were partial response, 7 cases were stable disease, the objective response rate was 65.0 % (13/20), and the histologically clearance rate of giant cells was 85.0 % (17/20). No case of osteonecrosis of the jaw was observed in this study, and all laboratory indicators were normal. The average postoperative MSTS-93 score was 26.87. Compared with pelvic GCTB patients who underwent surgical treatment from 1999 to 2009, in the intralesional surgery group, there was no significant difference in the recurrence rate [15.4 % (2/13) vs. 30.8 % (4/13), P = 0.514], but the limb function was significantly increased (P= 0.002). Conclusions Denosumab combined with surgery plays an important role in the multidisciplinary treatment of pelvic GCTB. The neoadjuvant strategy can reduce patient's intraoperative blood loss by shrinking the tumor size which makes the intralesional curettage surgery possible, and also diminishing the recurrence rate. But more attention should be paid to secondary malignant GCTB during the use of denousmab.
ABSTRACT
Objective To evaluate the clinical benefits of denosumab in treatment of sacral giant cell tumor of bone(GCTB) when used preoperatively or postoperatively along with surgery, and to analysis the improvement of sacral nerve function. Methods Thirty patients diagnosed as sacral GCTB in Musculoskeletal Tumor Center of Peking University People's Hospital from April 2014 to July 2016 were divided into control group (10 cases), post-operative group (9 cases), and neoadjuvant group (11 cases). Patients in the post-operative and neoadjuvant group were treated with 120 mg of subcutaneous denosumab every 4 weeks with loading doses on days 8 and 15 of the first cycle. Results Three patients in the control cohort 1 had recurrence (3/10), no recurrence occurred in the post-operative group (0/9), and 3 patients in the neoadjuvant group had recurrence(3/11).There were no significant differences in event-free survival(EFS) among the three groups (P = 0.133). The objective response rate (OTR) was 63.6 % (7/11) in the neoadjuvant group based on the RECIST 1.1 criteria for evaluating the efficacy of solid tumors. Five cases had significant pain improvement (defined 2 points improved) and had much better bladder and bowel functions. Four patients were able to have their indwelling catheters removed after neoadjuvant denosumab treatment. Conclusions Neoadjuvant therapy with denosumab can relieve the symptoms and neurologic deficits caused by nerve compression and can diminish the intraoperative blood loss. Surgical removal of the tumor is still the basic treatment of sacral GCTB.