Current evidence and challenges of systematic therapies for adult recurrent glioblastoma: Results from clinical trials

Recurrence is a major concern for adult patients with glioblastomas(GBMs), and the prognosis remains poor.Although several therapies have been assessed, most of them have not achieved satisfactory results. Therefore, there is currently no standard treatment for adult recurrent GBM(r GBM). Here, we review the results of clinical trials for the systematic therapy of r GBM. Regorafenib, rindopepimut and neoadjuvant programmed death 1(PD-1)inhibitors are promising agents for r GBM, while regorafenib is effective in both O6-methylguanine DNA methyltransferase(MGMT) promoter methylated and unmethylated patients. Temozolomide rechallenge and alkylating agents combined with bevacizumab can be useful for patients with MGMT methylation, and patients with isocitrate dehydrogenase(IDH) mutations or second recurrence can benefit from vocimagene amiretrorepvec(Toca511). Some phase I trials on targeted therapy and immunotherapy have shown positive results, and results from further studies are expected. In addition to the analysis of existing clinical trial results, forthcoming trials should be well designed, and patients are encouraged to participate in appropriate clinical trials.

Is Manipulative Therapy Clinically Necessary for Relief of Neck Pain？A Systematic Review and Meta-Analysis

Objective：To summarize and critically assess the efficacy of Eastern and Western manipulative therapies for the treatment of neck pain in adults. Methods：A search of Pub Med/MEDLINE, the Cochrane Central Register of Controlled Trials, Clinical Trials.gov, EMBASE, etc. from their inception date to January 2014 with Chinese, Japanese, and Korean databases. Two reviewers independently selected randomized controlled trials（RCTs） with negative control or blank control, extracted data and assessed methodological quality. Meta-analysis and levels of evidence were performed by Revman5.1 and Grades of Recommendations Assessment, Development and Evaluation（GRADE） approach. Results：Nineteen clinical trials with adequate randomization were included in this review, 11 of them had a low risk of bias. The primary outcome for shortterm pain had no significant differences, however, the secondary outcome, only the Numerical Pain Rating Scale（NPRS） score of intermediate-term [n=916, pooled mean differences（MD） =–0.29, P=0.02], the Neck Disability Index（NDI） score of short-term（n=1,145, pooled MD=–2.10, P〈0.01）, and intermediate-term（n=987, pooled MD=–1.45, P=0.01） were significantly reduced with moderate quality evidence. However, it supported the minimally clinically important difference（MCID） of the Visual Analogue Scale and NPRS pain score to be 13 mm, while NDI was 3.5 points. The meta-analysis only suggested a trend in favor of manipulative therapy rather than clinical significance. Conclusions：The results do not support the existing evidences for the clinical value of Eastern or Western manipulative therapy for neck pain of short-term follow-up according to MCIDs. The limitations of our review related to blinding, allocation concealment and small sample size.

Effectiveness of bee venom acupuncture in alleviating post-stroke shoulder pain: a systematic review and meta-analysis

BACKGROUND：Shoulder pain is a common complication of stroke.Bee venom acupuncture（BVA）is increasingly used in the treatment of post-stroke shoulder pain.OBJECTIVE：To summarize and evaluate evidence on the effectiveness of BVA in relieving shoulder pain after stroke.SEARCH STRATEGY：Nine databases,namely MEDLINE,EMBASE,the Cochrane Library,the China National Knowledge Infrastructure（CNKI）,the Japan Science and Technology Information Aggregator,Electronic（J-STAGE）,and four Korean medical databases,namely,the National Assembly Library,the Research Information Service System,the National Discovery for Science Leaders,and OASIS,were searched from their inception through August 2014 without language restrictions.INCLUSION CRITERIA：Randomized controlled trials（RCTs）were included if BVA was used at acupoints as the sole treatment,or as an adjunct to other treatments,for shoulder pain after stroke.DATA EXTRACTION AND ANALYSIS：Two review authors independently selected trials for inclusion,assessed methodological quality and extracted data.RESULTS：A total of 138 potentially relevant articles were identifi ed,4 of which were RCTs that met our inclusion criteria.The quality of studies included was generally low,and a preponderance of positive results was demonstrated.All four trials reported favorable effects of BVA on shoulder pain after stroke.Two RCTs assessing the effects of BVA on post-stroke shoulder pain,as opposed to saline injections,were included in the meta-analysis.Pain was signifi cantly lower for BVA than for saline injections（standardized mean difference on 10-cm visual analog scale：1.46 cm,95%CI=0.30–2.62,P=0.02,n=86）CONCLUSION：This review provided evidence suggesting that BVA is effective in relieving shoulder pain after stroke.However,further studies are needed to confi rm the role of BVA in alleviating post-stroke shoulder pain.Future studies should be conducted with large samples and rigorous study designs.