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Novel recursive partitioning analysis classification for newly diagnosed glioblastoma: A multi-institutional study highlighting the MGMT promoter methylation and IDH1 gene mutation status

 Chan Woo Wee  ;  Eunji Kim  ;  Nalee Kim  ;  In Ah Kim  ;  Tae Min Kim  ;  Yu Jung Kim  ;  Chul-Kee Park  ;  Jin Wook Kim  ;  Chae-Yong Kim  ;  Seung Hong Choi  ;  Jae Hyoung Kim  ;  Sung-Hye Park  ;  Gheeyoung Choe  ;  Soon-Tae Lee  ;  Jong Hee Chang  ;  Se Hoon Kim  ;  Chang-Ok Suh  ;  Il Han Kim 
 RADIOTHERAPY AND ONCOLOGY, Vol.123 : 106-111, 2017 
Journal Title
Issue Date
Adult ; Aged ; Brain Neoplasms/drug therapy ; Brain Neoplasms/genetics* ; DNA Methylation* ; DNA Modification Methylases/genetics* ; DNA Repair Enzymes/genetics* ; Dacarbazine/analogs & derivatives ; Dacarbazine/therapeutic use ; Female ; Glioblastoma/drug therapy ; Glioblastoma/genetics* ; Humans ; Isocitrate Dehydrogenase/genetics* ; Male ; Middle Aged ; Mutation* ; Promoter Regions, Genetic* ; Tumor Suppressor Proteins/genetics*
Glioblastoma ; Isocitrate dehydrogenase ; MGMT ; Recursive partitioning analysis ; Temozolomide
BACKGROUND AND PURPOSE: To refine the recursive partitioning analysis (RPA) classification for glioblastoma incorporating the MGMT methylation and IDH1 mutation status. METHODS AND MATERIALS: 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. RESULTS: 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). CONCLUSIONS: 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.
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1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Nalee(김나리) ORCID logo https://orcid.org/0000-0003-4742-2772
Kim, Se Hoon(김세훈) ORCID logo https://orcid.org/0000-0001-7516-7372
Suh, Chang Ok(서창옥)
Chang, Jong Hee(장종희)
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