The Prognosis Influence Of MRI Signs And IDH Gene Phenotype In Post-treatment Lower Grade Glioma: A Preliminary Study

Part 1 Prognostic value of relative signal intensity of FLAIR outside the residual cavity in lower grade glioma: a preliminary studyObjective: Fluid attenuated inversion recovery(FLAIR)hyperintense outside the residual cavity is one of the important MRI features in lower grade gliomas(LGG),but its prognostic value needs to be further explored.This pilot study aimed to investigate whether the relative signal intensity of FLAIR outside the residual cavity(r FLAIR)can help to improve the predictive performance of survival assessment in post-treatment LGG patients.Methods:We retrospectively analyzed clinical and MRI data of 152 post-treatment LGG.Image J software was used to measure the gray values of FLAIR outside the residual cavity and contralateral normal brain parenchyma,and the background.We calculated r FLAIR by the difference of the gray values of FLAIR outside the residual cavity and the background comparing the contralateral normal brain parenchyma and the background.Based on Response Assessment in Neuro-Oncology(RANO)criteria,the LGG patients were divided into progression and non-progression groups.Chi-square test and Mann-Whitney U test were used to compare the differences of clinical variables,conventional MRI factors and r FLAIR between the two groups.Univariate and multivariate analysis were used to explore the significant clinical variables,conventional MRI factors and r FLAIR on progression free survival(PFS)and overall survival(OS).Clinical model,conventional MRI model and the combined model(clinical + conventional MRI model and clinical + conventional MRI + r FLAIR model)were established to predict survival prognosis of LGG.Receiver operating characteristic curves(ROC)was employed to evaluate the diagnostic efficacy of these models.Survival analysis was made with Kaplan-Meier method.The intraclass correlation coefficient(ICC)was used to evaluate the consistency of the measurement of r FLAIR between two observers.Results: Significant differences in postoperative Karnofsky performance scale(KPS)score(P=0.002),Ki-67(P=0.014),WHO grades(P=0.012),isocitrate dehydrogenase(IDH)gene phenotype(P<0.001),1p19 q gene phenotype(P=0.007),residual cavity wall enhancement(P=0.001),new remote enhancement(P=0.006),subventricular zone(SVZ)involvement(P<0.001)and r FLAIR(P<0.001)were found between the progression and non-progression groups.Multivariate analysis showed that thick linear and nodular enhancement of the residual cavity wall,higher r FLAIR(>1.595)were independent factors for the poor prognosis of PFS and OS(both P <0.05),and SVZ involvement was an independent risk factor for poor prognosis of OS(P=0.011).Area under the ROC curve(AUC)for predicting poor PFS: clinical model 0.726,conventional MRI model 0.672,clinical + conventional MRI model 0.760,combined model(clinical + conventional MRI + r FLAIR)0.827;AUC for predicting OS: clinical model 0.799,conventional MRI model 0.735,clinical + conventional MRI model 0.843,combined model(clinical +conventional MRI + r FLAIR)0.880.The cut-off r FLAIR of 1.595 could be used to predict poor PFS(HR 0.27,95%CI 0.17-0.42)and OS(HR 0.22,95%CI 0.12-0.40)(both P<0.001).The ICC value of the r FLAIR measurement was 0.989(95%CI 0.986-0.992)(P<0.0001)between two observers.Conclusions:Our preliminary results indicated that higher r FALIR(>1.595)outside the residual cavity can be used as a biomarker of poor survival of LGG.Moreover,r FLAIR is helpful to improve the diagnostic performance of survival prediction of post-treatment LGG patients.Part 2 The influence of IDH gene phenotype on MRI signs and prognosis in post-treatment lower grade astrocytomaObjective: Preoperative MRI signs of gliomas with different isocitrate dehydrogenase(IDH)gene phenotype may affect the prognosis of patients.The purpose of this study was to evaluate the MRI signs in post-treatment lower grade astrocytoma(LGA)with different IDH gene phenotype and to analysis its effect on patients’ overall survival(OS).Methods:The clinical variables and MRI signs of 49 LGA,with IDH gene phenotype detected by polymerase chain reaction(PCR),were analysed retrospectively.LGA were divided into IDH mutant-type and IDH wild-type groups,and clinical factors(age,Ki-67,location,WHO grades)and post-treatment MRI signs(residual cavity wall enhancement,new remote enhancement,subventricular zone involvement,FLAIR hyperintense area change outside residual cavity,and relative FLAIR hyperintense of residual cavity)were analysed and researched the diagnostic efficacy of different factors.Chi-square test,t test and Mann-Whitney U test were used to analyse the factors;receiver operating characteristic curve(ROC)was used to evaluate different factors and the IDH gene phenotype to predict the diagnostic efficacy in post-treatment LGA.Results: The median follow-up time was 629(95%CI 516-731)days in49 LGA.IDH mutant-type group and IDH wild-type group had 26 and 23 cases,respectively.IDH wild-type group had higher WHO grades(P=0.035),Oxygen 6-methylguanine-DNA methyltransferase(MGMT)non-methylated state(P=0.043),thick linear and nodular enhancement of residual cavity wall(P=0.001),increased significantly FLAIR hyperintense area change outside residual cavity(P=0.014),and higher relative FLAIR hyperintense of residual cavity(P=0.001).ROC analysis showed that model combined IDH gene phenotype was more effective in predicting prognosis,with AUC was 0.914,sensitivity was 0.800,specificity was 0.941.Conclusions:Residual cavity wall tended to thick linear and nodular enhancement,FLAIR hyperintense area change outside residual cavity increased significantly,relative FLAIR hyperintense of residual cavity was higher in IDH wild-type post-treatment LGA.Model combined IDH gene phenotype could improve the diagnosis efficacy of patients’ survival.