Validation of a novel molecular RPA classification in glioblastoma (GBM-molRPA) treated with chemoradiation: A multi-institutional collaborative study

Radiother Oncol. 2018 Nov;129(2):347-351. doi: 10.1016/j.radonc.2018.09.001. Epub 2018 Sep 17.

Abstract

Background and purpose: A novel molecular recursive partitioning analysis classification has recently been reported integrating the MGMT promoter methylation (MGMTmeth) and IDH1 mutation (IDH1mut) status for glioblastoma (GBM-molRPA) patients treated with temozolomide-based chemoradiation. The current study was initiated to validate the model in a multi-institutional study.

Materials and methods: Four-hundred seventy-one newly diagnosed GBM patients (validation cohort) were allocated to classes I-III of the previously reported GBM-molRPA model. Of the patients, 15.7%, 56.1%, and 28.2% patients were GBM-molRPA class I, II, and III, respectively. MGMTmeth and IDH1mut were observed in 32.3 and 8.8% of patients, respectively. In the training plus validation cohort of 692 patients, 16.2%, 60.8%, and 23.0% patients were class I, II, and III, respectively.

Results: The median follow-up for survivors and the median survival (MS) of patients was 23.3 and 18.4 months, respectively. The MS for GBM-molRPA class I, II, and III was 49.7 (95% CI, 22.8-76.6), 19.2 (95% CI, 16.2-22.1), and 13.8 months (95% CI, 11.8-15.4) (P < .001 for all comparisons) in the validation cohort. In the training plus validation cohort, the MS was 58.5 (95% CI, 40.7-76.3), 21. (95% CI, 18.6-23.3), and 14.3 months (95% CI, 12.5-16.1) (P < .001 for all comparisons) for class I, II, and III, respectively.

Conclusion: The GBM-molRPA is a valid model. This GBM-molRPA classification can be useful in clinics and guiding patient stratification in future clinical trials.

Keywords: Glioblastoma; IDH1; MGMT; Recursive partitioning analysis; Validation.

Publication types

  • Multicenter Study
  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Brain Neoplasms / genetics
  • Brain Neoplasms / therapy*
  • Chemoradiotherapy / methods*
  • DNA Methylation
  • DNA Modification Methylases / genetics
  • DNA Repair Enzymes / genetics
  • Female
  • Glioblastoma / genetics
  • Glioblastoma / therapy*
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Male
  • Middle Aged
  • Mutation
  • Prognosis
  • Promoter Regions, Genetic / genetics
  • Temozolomide / therapeutic use
  • Tumor Suppressor Proteins / genetics

Substances

  • Tumor Suppressor Proteins
  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes
  • Temozolomide