The Relationship Between The Timing Of Postoperative Radiotherapy And The Prognosis Of High Grade Glioma

Background:High grade glioma is the most common primary central nervous system tumor in China.Its Morbidity and mortality are increasing year by year.It has the characteristics of high morbidity,high recurrence rate and high mortality.Currently,the treatment for high-grade glioma includes surgery,radiotherapy and chemotherapy.Despite the aggressive treatment,the patient's prognosis is poor.A number of retrospective studies have reported that clinically related adverse factors(such as age,KPS score,chemotherapy)can affect the prognosis of patients with high-grade glioma.However,there is still no clear answer about whether the waiting time of postoperative radiotherapy affects the prognosis of patients.Although the relationship between the waiting time of postoperative radiotherapy and the prognosis of patients has been researched in some types of tumors(such as breast cancer and head and neck tumors),it is suggested that delaying the waiting time of radiotherapy significantly reduces the local control rate of tumors and increases the local recurrence rate,thus affecting the long-term survival of patients.At present,the relationship between the waiting time of postoperative radiotherapy and the prognosis of patients with high-grade glioma is a controversial topic,and there is no unified conclusion.Therefore,it is of clinical significance to carry out a systematic review and meta-analysis about this problem.Methods:Literature retrieval was conducted from three databases including Pubmed,Embase,Cochrane.The search keyword inculded watiting?time?timing?interval?delay?prolong?initiation?glioma?glioblastoma?radiation?radiotherapy?chemoradiation?chemoradiotherapy?adjuvant,The search date was limited from January 1,1975 to November 1,2019 and no restrictions about study design,language and publication format.For the retrieved literatures,the non-conforming literatures were excluded according to the inclusion criteria.Literatures included in the systematic review were evaluated according to the NOS quality evaluation table.If the total score was less than7,it was considered as a low-quality literature,while only high-quality literatures could be included in the meta-analysis.The meta-analysis was performed by converting the effect size(HR)of different waiting time groups of postoperative radiotherapy into regression coefficient(?)and standard error(SE)to represent the effect of daily delay on total survival(OS)of patients.First,the fixed effect model was used to integrate the adjusted effect size of each study and the Cochrane Q and I2 tests were used to assess the consistency of the literatures.If I2 is greater than 50%,the heterogeneity is large and the random effect model should be changed to integrate the effect sizes.Funnel plot,Egger's test and Begg's test were used for the evaluation of publication bias,Symmetrical inverted funnel shape and P>0.05 indicated no significant publication bias.Meta regression was used to adjust for other prognostic factors(such as KPS score,age,chemotherapy,surgical resection)to further clarify the relationship between the waiting time of postoperative radiotherapy and the prognosis of high-grade glioma.Results:A total of 11135 literatures were retrieved from different databases.After eliminating the duplicate literatures,the 9874 literatures were preliminarily screened according to the title or abstract.Among them,44 literatures were screened.After further excluding unqualified literatures according to the inclusion criteria,the quality of 27 literatures was systematically evaluated.,Among them,the NOS quality scores of 7literatures were lower than 7 and finally,20 literatures were included for meta-analysis.A total of 8730 patients with high-grade glioma were included in these 20 literatures and no significant heterogeneity was observed between each study(Cochrane's Q test P>0.05,I2=26.3%<50%)and no significant publication bias was observed(Begg test,P=0.770 and Egger's test,P=0.719).In the unadjusted model,no significant correlation was found between the waiting time of postoperative radiotherapy and the total survival time(OS)of patients(HR=1,95%CI=0.997-1.003,P=0.876).After adjusting for other prognostic factors by meta-regression,there was still no clear evidence of correlation between the waiting time of postoperative radiotherapy and OS(P>0.05).Conclusions:The results of this systematic review and meta-analysis suggest that there is no clear evidence that the waiting time of postoperative radiotherapy effects the prognosis of patients with high-grade glioma,either in the unadjusted model or the meta-regression model.