Meta-analysis Of The Efficacy And Safety Of Immunotherapy For Glioma

BackgroundGliomas originate from glial cells,accounting for about 40%of primary brain tumors.World Health Organization(WHO)classifies gliomas into I-IV grades according to histopathological and molecular parameters.The traditional treatment is including the maximum degree of surgical resection plus radiotherapy and chemotherapy.Despite the development of traditional treatment,the prognosis of glioma patients is still poor.It is reported that the most aggressive and heterogeneous glioblastoma patients survive less than 15 months after conventional treatment.Therefore,to develop a new and effective treatment is an urgent need for glioma patients.With an in-depth understanding of glioma biology,immunotherapy has attracted wide attention.Immunotherapy has the advantage of targeting tumor cells,it has become a promising method for the treatment of gliomas.Recently,many high-quality preclinical and clinical studies have been conducted to evaluate the efficacy and safety of immunotherapy for glioma,lacking comprehensive evaluation.Based on the principles of evidence-based medicine,we conducted a systematic review and meta-analysis to provide reference for further research and clinical application of immunotherapy for glioma.ObjectThis systematic review and meta-analysis aim to evaluate the overall efficacy and safety of immunotherapy for glioma and find out the preferable immunotherapy strategies.MethodsThe PubMed,Embase,Web of Science,and Ovid databases were searched in August 2019 and updated in June 2020.The strategy complied with the PRISMA guidelines.We included studies that evaluated the efficacy and safety of immunotherapy for glioma.All studies should implement the method of randomized control.The quality of the included studies was evaluated by "improved STAR(The initial Stroke Therapy Academic Industry Roundtable)criteria" and"The Cochrane Collaboration’s tool for assessing risk of bias in randomized trials".Revman 5.3 was used for meta-analysis,R software 4.2 was used for Bayesian network meta-analysis.ResultsOverall,7 preclinical and 15 clinical studies with randomization were included in the pairwise meta-analysis,and 16 randomized clinical studies were included in a Bayesian network meta-analysis.Meta-analysis focuses on comprehensively evaluating the efficacy and safety of immunotherapy,and Bayesian network meta-analysis focuses on finding the preferable treatment..According to the pairwise meta-analysis,the preclinical data demonstrated a significant reduction in tumor growth after 2 weeks of immunotherapy(standardized mean difference=-2.64,p=0.0004).The clinical studies revealed that immunotherapy significantly improved overall survival(OS)(hazard ratio=0.91,p=0.02)and progression-free survival(PFS)(hazard ratio=0.75,p=0.0005).However,immunotherapy was associated with an increased risk of 1-5 grade adverse events(OR=2.51,p=0.0008)and≥3 grade adverse events(OR=2.16,p<0.00001).The bay sin network meta-analysis verified that Cytokine-induced natural killer cell(CIK)vaccines were probably the best at improving survival effects(52%),bevacizumab was the best at improving progression-free survival effects(51%).Cytokine-induced killer cell+conventional therapy(CT),bevacizumab(BEV)+ CT,and dendritic cell(DC)vaccine+CT are considered as preferable choices.ConclusionsThis analysis demonstrated that immunotherapy suppressed tumor growth in animal models and improved OS and PFS of glioma patients.Treatments with CIK,BEV,and DC vaccines are preferable in terms of efficacy.However,the risk of adverse events was increased.