Real-world Study Of Glioma Based On WHO CNS5 Classification

Part Ⅰ:Analysis of Clinical Characteristics and Establishment of Survival Prediction Model for Glioma Based on the 5th Edition of WHO Classification of Central Nervous System Tumors.Objective:The 5th edition of the World Health Organization(WHO)classification of central nervous system tumors incorporated specific molecular alterations into the categorization of gliomas.The substantial revision of the classification scheme effectuates major changes in the diagnosis and treatment of glioma.This study aimed to depict the clinical,molecular,and prognostic characteristics of glioma and its subtypes under the current WHO classification.By using machine learning models to determine the most important prognostic indicators for glioma patients,we can predict their prognosis.Methods:Patients undergoing surgery for gliomas at Peking Union Medical College Hospital during 11 years were re-examined for tumor genetic alterations using next-generation sequencing,polymerase chain reaction-based assay,and fluorescence in situ hybridization methods and enrolled in the analysis.And verify the factors that affect prognosis through machine learning screening.Results:The enrolled 452 gliomas were re-classified into adult-type diffuse glioma pediatric-type diffuse glioma,circumscribed astrocytic glioma,and glioneuronal and neuronal tumor.The composition,definition,and incidence of adult-and pediatric-type gliomas changed greatly from the 4th to the 5th edition of classification.The clinical,radiological,molecular,and survival characteristics of each subtype of gliomas were identified.Alterations in CDK4/6,CIC,FGFR2/3/4,FUBP1,KIT,MET,NF1,PEG3,RB1,and NTRK2 were additional factors correlated with the survival of different subtypes of gliomas.A risk scoring system composed of seven variables including age,FGFR2,IDH1,CDK4,CDK6,KIT and CDKN2A has been constructed through machine learning to effectively predict patient prognosis.Conclusions:We have presented a comprehensive classification of gliomas under the WHO CNS5 classification,and described the clinical,radiological,molecular and survival characteristics of each subtype.Additional biomarkers that may have prognostic potential have been identified,highlighting the value of histological and molecular integrated classification schemes.A new predictive prognostic model has been developed through machine learning.Part Ⅱ:Clinical Characteristics and Prognostic Study of Astrocytoma Based on the 5th Edition WHO Classification of Central Nervous System TumorsPurpose:The diagnosis of glioma has got an advance since the WHO 2021 classification published with more molecular alternations involved in the integrate diagnoses pathways.Our study was aimed to show our experience on the clinical features and management of astrocytoma,IDH-mutant based on latest WHO classification.Methods:Patients diagnosed with astrocytoma,IDH-mutant based on WHO 5th edition classification of CNS tumors at our center from Jan 2009 to Jan 2022 were included,and divided to WHO 2-3 grade group and WHO 4 grade group.Integrate diagnoses according to WHO CNS4 and CNS5 classification were confirmed retrospectively.Clinical and MRI features were reviewed and survival analysis was done.Results:A total of 60 patients were included.21.67%of(13/60)all patients changed tumor grade from WHO 4th edition classification to 5th classification,and 21.43%(6/28)of patients diagnosed with grade Ⅱ and 58.33%(7/12)of patients with grade III by WHO 4th edition classification changed into grade 4 by WHO 5th classification.Sex(p=0.042),recurrent glioma(p=0.006)and Ki-67 index(p<0.001)of pathological exam were statistically different in WHO grade 2-3 group(n=27)and WHO grade 4 group(n=33).CDK6(p=0.004).FGFR2(p=0.003).MYC(p=0.004)alterations shown an enrichment in WHO grade 4 group.Patients with higher grade shown shorter mOS(mOS=75.9m,53.6m.26.4m for grade 2,3,4 respectively,p=0.01).FGFR2 alternations was associated with worse survival for patients with astrocytoma,IDH-mutant.WHO grade 4(p=0.013).Variations of BCOR,MYCN.NOTCH1 and PIK3R1 and immunohistochemistry positive of S1009 also had an association with worse survival in WHO grades 4 astrocytoma(Supplementary figure 2).For grades 2-3 astrocytoma,variations of FGFR4,KIT,NTRK2 and immunohistochemistry positive of ATRX and EGFR were significantly related to worse survival.Conclusions:Patients with poorer prognosis are more likely to be diagnosed as WHO grade 4 by WHO 5th edition classification based on molecular alternations compared with former classification,and treatment should be tailored personally for them.More researches of the management of IDH-mutant astrocytoma are needed in the future.