| ObjectivesGlioma accounts for about 80%of all malignant brain tumors and is the primary malignant tumor in the central nervous system.Radiation and surgery are currently the main treatments for glioma.Since some patients with glioma may have seizures after surgery,valproic acid（VPA）is used as a clinically commonly used anti-epileptic drug for the clinical treatment of patients.Through a variety of tumor cells and animal models,we and other research groups have proved that VPA can enhance the killing effect of radiation on tumor tissue cells at the cellular and animal levels.However,the radiosensitization effect of VPA on tumors needs to be passed more critically.Analysis and verification of clinical data.To this end,this study retrospectively analyzed the clinical case data of 134 patients with glioma who underwent radiotherapy and surgery.Through the analysis of the effect of VPA on the prognosis of patients and tumor recurrence,the study specifically studied the effect of VPA on tumors from a clinical perspective.The radiation sensitization effect of glioma is designed to provide reliable experimental basis for the clinical treatment of patients with glioma,and the research has important clinical application value and guiding significance.MethodsThis retrospective study collected clinical data of patients with glioma admitted to Qilu Hospital,Jinan City,Shandong Province from January 2012 to December 2016.According to the inclusion criteria,134 patients with glioma were included in the study.Through the electronic medical record query system of the Oncology Department of Qilu Hospital,Jinan City,Shandong Province,the following information of patients is collected and entered:contact information,first and last admission time,age,gender,height,weight,body mass index（BMI）,smoking status,allergy history,Past history,whether or not surgery,operation time,pathological grade,whether or not radiotherapy,start time of radiotherapy,radiotherapy dose,whether chemotherapy,chemotherapy dose,whether to take VPA,VPA dosage,etc.Based on the above information,a study on the effect of VPA on overall survival（OS）and progression free survival（PFS）of 134 patients was carried out.OS and PFS are mainly obtained through multiple follow-ups,which are followed up by telephone,hospitalization or outpatient review.The overall survival period is from the date of diagnosis to the date of death or the date of the last follow-up,and the progression-free survival period is from the date of diagnosis to the date of tumor recurrence or the date of the last follow-up.If the patient dies outside the hospital,it can be obtained by contacting the patient’s relatives.Patients who cannot be contacted due to various reasons are lost to follow-up.The survival time of lost patient is calculated based on the last follow-up date.Survival data is calculated in months.The deadline for follow-up in this study is December 30,2019.This research uses SPSS 22.0 statistical software to process the data.Categorical variables are expressed in the form of n（%）,and Pearson’s□2 test is used for the variation between groups of each variable.Single factor analysis was used to explore VPA exposure（yes/no）,gender（male,female）,age（<45 years old/≥45 years old）,BMI（<24 kg/m2/≥24 kg/m2）,smoking（yes/No）,pathological grade（low grade/high grade）,whether chemotherapy（yes/no）affects OS and PFS,the P<0.05 index in the analysis was included in the Cox model for multivariate analysis.The age,pathological grade,and whether chemotherapy is stratified,and the effects of VPA exposure on OS and PFS are further analyzed.The multiplication terms of VPA exposure and age,pathological grade,and chemotherapy are placed in the model to study the relationship between VPA exposure and the above-mentioned scores.The interaction of layer variables on OS and PFS.In this study,a two-sided test was used,and the test level a was 0.05.Results1.The Basic Clinical Characteristics of 134 Glioma PatientsOf the 134 glioma patients included in this study until the end of the last follow-up,76 patients died and 67 relapsed.All patients underwent surgery and radiation therapy.There were 71 cases of VPA exposed and 63 cases of non-exposure.Among them,the difference between VPA exposure and the non-exposure group was statistically significant.Age,gender,BMI,pathological grade,and smoking were not statistically significant.The median age of the patients was 48 years（8-78）,including 71 males（52.99%）and 63 females（47.01%）;There were 74 cases（55.22%）in the BMI<24 kg/m2 group and 60 cases（44.78%）in the BMI≥24 kg/m2 group;23 cases（17.16%）in the smoking group,111 cases（82.84%）in the non-smoking group;49 cases（36.57%）in low-grade glioma patients,high-grade glioma There were 85 cases（63.43%）of mass tumor patients;68 cases（50.75%）in the chemotherapy group and 66 cases（49.25%）in the non-chemotherapy group.2.Patients’ survival time analysis of 134 glioma patientsThrough Kaplan-Meier’s OS and PFS analysis of 134 patients with glioma,the estimated median overall survival time for all patients was 52 months,and the one-year,three-year and five-year overall survival rates were 86.6%,60.6%and 47.7%.The estimated median progression-free survival time for patients is 49 months,and the one-,three-,and five-year progression-free survival rates are 84.0%,59.3%,and 47.0%.3.Single-factor analysis of the influence of VPA and other factors on OS and PFS in patients with radiotherapy gliomaThe univariate analysis of the effect of VPA on OS and PFS in patients with glioma showed that VPA exposure was a prognostic factor of OS and PFS in patients with glioma after radiotherapy（HR=0.47,95%CI:0.30～0.75;HR=0.51,95%CI:0.31～0.83）.In addition,in order to confirm the reliability of VPA results,we also analyzed the influence of the reported prognostic factors of glioma patients,such as age,pathological grade and chemotherapy,on OS and PFS of glioma patients.The results of OS analysis affecting patients with glioma showed age（HR=2.22,95%CI:1.37～3.61）,pathological grade（HR=3.58,95%CI:2.02～6.32）,and chemotherapy（HR=0.17,95%CI:0.10-0.30）are related to the prognosis of patients,while gender,BMI and smoking have no significant effect on the prognosis.The results of PFS analysis of glioma patients showed that age（HR=2.02,95%CI:1.22～3.34）,pathological grade（HR=3.01,95%CI:1.71～5.31）and chemotherapy（HR=0.23,95%CI:0.13～0.39）were related to the prognosis of patients,while gender,BMI and smoking had no significant effect on the prognosis（P>0.05）.Based on the above results of this study:age,pathological grade and chemotherapy have influence on OS and PFS of glioma patients,and gender,BMI and smoking have no influence on OS and PFS of glioma patients,which are consistent with the current reports.It also shows that VPA exposure is a reliable prognostic factor for OS and PFS of glioma patients after radiotherapy.4.Multi-factor analysis of the influence of VPA and other factors on OS and PFS in patients with radiotherapy for gliomaThe factors with a P value less than 0.05 in the univariate analysis were included in the Cox regression model for multivariate analysis.The results showed that:（1）VPA exposure is an independent prognostic factor for OS and PFS in patients with postoperative radiotherapy for glioma.The risk of death in patients taking VPA is 0.49 times that of non-VPA,and the risk of tumor recurrence is that of non-VPA.（2）Age is an independent poor prognostic factor that affects OS in patients with postoperative radiotherapy for glioma.The risk of death in patients ≥45 years old is 1.74 times that of<45 years old,but age is not an independent prognostic effect of PFS Factors;（3）Pathological grade is an independent adverse prognostic factor that affects OS and PFS in patients with postoperative radiotherapy for glioma.The risk of death in patients with high-grade（Ⅲ-Ⅳ）glioma is low-grade（Ⅰ-Ⅱ）),the risk of tumor recurrence is 2.61 times that of low-grade;（4）Chemotherapy is an independent adverse prognostic factor that affects OS and PFS in patients with postoperative radiotherapy for glioma,and the risk of death in chemotherapy patients is that of non-chemotherapy patients The risk of tumor recurrence in patients with chemotherapy is 0.29 times that of patients without chemotherapy.These results further suggest that VPA exposure is an independent prognostic factor for OS and PFS in patients with glioma after radiotherapy.5.Interaction between VPA exposure and chemotherapy,age,and pathological grade in patients with radiotherapy for gliomaBecause the above results suggest that VPA and age,pathological grade,and whether or not chemotherapy have a significant impact on the patient’s OS and PFS,this study further explored the relationship between VPA and these by stratified analysis of whether the patient was receiving chemotherapy,age,and pathological grade.Correlation between influencing factors.The results of OS analysis showed that the HR of VPA exposure in the chemotherapy group and the non-chemotherapy group were 0.41（95%CI:0.15～1.17）and 0.59（95%CI:0.32～1.09）,respectively,in the<45 years old group and the≥45 years old group The HR of VPA exposure was 0.67（95%CI:0.24～1.83）and 0.52（95%CI:0.29～0.92）.The low-level（Ⅰ-Ⅱ）group and the high-level（Ⅲ～Ⅳ）group were exposed to VPA.HR were 0.28（95%CI:0.07～1.09）and 0.57（95%CI:0.33～0.98）,respectively.The results of the PFS analysis showed that the HR of VPA exposure in the chemotherapy group and the non-chemotherapy group was 0.42（95%CI:0.16～1.08）and 0.71（95%CI:0.36～1.38）,respectively,the<45 years old group and the,45 years old group The HRs of VPA exposure were 0.87（95%CI:0.32～2.41）and 0.51（95%CI:0.27～0.94）.The low-grade（Ⅰ～Ⅱ）group and the high-grade（Ⅲ～Ⅳ）group were exposed to VPA.HR were 0.31（95%CI:0.09～1.06）and 0.63（95%CI:0.35～1.14）.There is no interaction between VPA exposure and pathological grade,age,and whether or not to chemotherapy on OS and PFS.It indicates that the prognostic effect of glioma patients taking VPA is not affected by pathological grade,age,and chemotherapy.Conclusions1.In addition to known factors such as age,tumor pathological grade,and chemotherapy,VPA is also a factor affecting the prognosis of patients with glioma.2.VPA can significantly improve the survival time of patients with glioma after postoperative radiotherapy and reduce tumor recurrence.The prognostic effect of VPA in patients with glioma is not affected by age,pathological grade,and the chemotherapy drug temozolomide. |
PDF Full Text Request