title: Novel recursive partitioning analysis classification for newly diagnosed glioblastoma: A multi-institutional study highlighting the MGMT promoter methylation and IDH1 gene mutation status.
abstract: To refine the recursive partitioning analysis (RPA) classification for glioblastoma incorporating the MGMT methylation and IDH1 mutation status.
  
  
  
  Three-hundred forty patients were treated with radiotherapy plus concurrent and adjuvant temozolomide in three tertiary-referral hospitals. MGMT methylation and IDH1 mutation status were available in all patients. Methylation of the MGMT (MGMTmeth) and mutation of IDH1 (IDH1mut) were observed in 42.4% and 6.2% of the patients, respectively.
  
  
  
  The median follow-up for survivors and all patients was 33.2 and 20.5months, respectively. The median survival (MS) was 23.6months. RPA was performed on behalf of the results of the Cox proportional hazards model. MGMT methylation generated the initial partition (MGMTmeth vs. MGMTunmeth) in the RPA. Three final RPA classes were identified; class I=MGMTmeth/IDH1mut or MGMTmeth/IDH1wt/GTR/KPS≥90 (MS, 67.2months); class II=MGMTmeth/IDH1wt/GTR/KPS<90, MGMTmeth/IDH1wt/residual disease, MGMTunmeth/age<50, or MGMTunmeth/age≥50/GTR (MS, 24.0months); class III=MGMTunmeth/age≥50/residual disease (MS, 15.2months).
  
  
  
  A novel RPA classification for glioblastoma was formulated highlighting the impact of MGMTmeth and IDH1mut in the temozolomide era. This model integrating pertinent molecular information can be used effectively for the patient stratification in future clinical trials. An external validation is ongoing.
authors.affiliation: Department of Radiation Oncology, Seoul National University College of Medicine, Republic of Korea.
authors.forename: Chan Woo
authors.initials: CW
authors.lastname: Wee
authors.affiliation: Department of Radiation Oncology, Seoul National University College of Medicine, Republic of Korea.
authors.forename: Eunji
authors.initials: E
authors.lastname: Kim
authors.affiliation: Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Nalee
authors.initials: N
authors.lastname: Kim
authors.affiliation: Department of Radiation Oncology, Seoul National University College of Medicine, Republic of Korea.
authors.forename: In Ah
authors.initials: IA
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Republic of Korea.
authors.forename: Tae Min
authors.initials: TM
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Republic of Korea.
authors.forename: Yu Jung
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Neurosurgery, Seoul National University College of Medicine, Republic of Korea.
authors.forename: Chul-Kee
authors.initials: CK
authors.lastname: Park
authors.affiliation: Department of Neurosurgery, Seoul National University College of Medicine, Republic of Korea.
authors.forename: Jin Wook
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Neurosurgery, Seoul National University College of Medicine, Republic of Korea.
authors.forename: Chae-Yong
authors.initials: CY
authors.lastname: Kim
authors.affiliation: Department of Radiology, Seoul National University College of Medicine, Republic of Korea.
authors.forename: Seung Hong
authors.initials: SH
authors.lastname: Choi
authors.affiliation: Department of Radiology, Seoul National University College of Medicine, Republic of Korea.
authors.forename: Jae Hyoung
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Republic of Korea.
authors.forename: Sung-Hye
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Republic of Korea.
authors.forename: Gheeyoung
authors.initials: G
authors.lastname: Choe
authors.affiliation: Department of Neurology, Seoul National University College of Medicine, Republic of Korea.
authors.forename: Soon-Tae
authors.initials: ST
authors.lastname: Lee
authors.affiliation: Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jong Hee
authors.initials: JH
authors.lastname: Chang
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Se Hoon
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: cosuh317@yuhs.ac.
authors.forename: Chang-Ok
authors.initials: CO
authors.lastname: Suh
authors.affiliation: Department of Radiation Oncology, Seoul National University College of Medicine, Republic of Korea. Electronic address: ihkim@snu.ac.kr.
authors.forename: Il Han
authors.initials: IH
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics*; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011401:Promoter Regions, Genetic; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077204:Temozolomide
keywords: Glioblastoma; Isocitrate dehydrogenase; MGMT; Recursive partitioning analysis; Temozolomide