Abstract
Glioblastoma accounts for more than half of diffuse gliomas. The prognosis of patients with glioblastoma remains poor despite comprehensive and intensive treatments. Furthermore, the clinical significance of molecular parameters and routinely available clinical variables for the prognosis prediction of glioblastomas remains limited. The authors describe a novel model may help in prognosis prediction and clinical management of glioblastoma patients. We performed a recursive partitioning analysis to generate three independent prognostic classes of 103 glioblastomas patients from TCGA dataset. Class I (MGMT promoter methylated, age <58), class II (MGMT promoter methylation, age ≥58; MGMT promoter unmethylation, age <54, KPS ≥70; MGMT promoter unmethylation, age >59, KPS ≥70), class III (MGMT promoter unmethylation, age 54-58, KPS ≥70; MGMT promoter unmethylation, KPS <70). Age, KPS and MGMT promoter methylation were the most significant prognostic factors for overall survival. The results were validated in CGGA dataset.This was the first study to combine various molecular parameters and clinical factors into recursive partitioning analysis to predict the prognosis of patients with glioblastomas. We included MGMT promoter methylation in our study, which could give better suggestion to patients for their chemotherapy. This clinical study will serve as the backbone for the future incorporation of molecular prognostic markers currently in development. Thus, our recursive partitioning analysis model for glioblastomas may aid in clinical prognosis evaluation.
Highlights
Glioblastoma (GBM) accounts for the majority of diffuse gliomas in adults [1]
103 patients with GBM were enrolled from The Cancer Genome Atlas (TCGA) as training set and 116 GBM patients from CGGA were constituted the validation set (Table 1)
We identified a primary split corresponding to MGMT promoter methylation status and secondary splits corresponding to age and Karnofsky performance scale (KPS)
Summary
Glioblastoma (GBM) accounts for the majority of diffuse gliomas in adults [1]. Despite intense efforts over the past several decades, the prognosis of patients with malignant glioma, glioblastoma, remains dismal [2]. The median overall survival (OS) of patients with GBM is approximately 15–17 months with the current gold-standard first-line treatment, which is maximal safe resection and combination of radiotherapy with temozolomide chemotherapy [1,2,3,4]. The combination of molecular markers as directive signatures with radiotherapy and chemotherapy could be a promising treatment approach for patients with GBM. IDH1/2, ATRX, 1p19q codeletion, TERT and MGMT promoter methylation), which were found to be highly associated with patient prognosis and glioma heterogeneity. MGMT promoter methylation blocks MGMT protein expression and is predictive of chemotherapy sensitivity, to alkylating agents such as temozolomide in patients with GBM www.impactjournals.com/oncotarget [5, 6]. Further investigation is needed to determine how to weight the relative importance of molecular parameters and clinical factors and incorporate them into prognostication and treatment decisions
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