scholarly journals Molecular Predictors of Progression-Free and Overall Survival in Patients With Newly Diagnosed Glioblastoma: A Prospective Translational Study of the German Glioma Network

2009 ◽  
Vol 27 (34) ◽  
pp. 5743-5750 ◽  
Author(s):  
Michael Weller ◽  
Jörg Felsberg ◽  
Christian Hartmann ◽  
Hilmar Berger ◽  
Joachim P. Steinbach ◽  
...  
Keyword(s):  
Overall Survival ◽  
Promoter Methylation ◽  
Genetic Alterations ◽  
Mgmt Promoter Methylation ◽  
Response To Therapy ◽  
Standards Of Care ◽  
Isocitrate Dehydrogenase 1 ◽  
Mutational Status ◽  
Mgmt Promoter ◽  
Idh1 Mutations

Purpose The prognostic value of genetic alterations characteristic of glioblastoma in patients treated according to present standards of care is unclear. Patients and Methods Three hundred one patients with glioblastoma were prospectively recruited between October 2004 and December 2006 at the clinical centers of the German Glioma Network. Two hundred fifty-eight patients had radiotherapy, 199 patients had temozolomide, 189 had both, and seven had another chemotherapy as the initial treatment. The tumors were investigated for TP53 mutation, p53 immunoreactivity, epidermal growth factor receptor, cyclin-dependent kinase CDK 4 or murine double minute 2 amplification, CDKN2A homozygous deletion, allelic losses on chromosome arms 1p, 9p, 10q, and 19q, O6-methylguanine methyltransferase (MGMT) promoter methylation, and isocitrate dehydrogenase 1 (IDH1) mutations. Results Median progression-free (PFS) and overall survival (OS) were 6.8 and 12.5 months. Multivariate analysis revealed younger age, higher performance score, MGMT promoter methylation, and temozolomide radiochemotherapy as independent factors associated with longer OS. MGMT promoter methylation was associated with longer PFS (relative risk [RR], 0.5; 95% CI, 0.38 to 0.68; P < .001) and OS (RR, 0.39; 95% CI, 0.28 to 0.54; P < .001) in patients receiving temozolomide. IDH1 mutations were associated with prolonged PFS (RR, 0.42; 95% CI, 0.19 to 0.91; P = .028) and a trend for prolonged OS (RR, 0.43; 95% CI, 0.15 to 1.19; P = .10). No other molecular factor was associated with outcome. Conclusion Molecular changes associated with gliomagenesis do not predict response to therapy in glioblastoma patients managed according to current standards of care. MGMT promoter methylation and IDH1 mutational status allow for stratification into prognostically distinct subgroups.

Methylation of MGMT in paired primary and recurrent GBMs.

2012 ◽  
Vol 30 (30_suppl) ◽  
pp. 65-65
Author(s):  
Li Bie ◽  
Feng Xian Zhang
Keyword(s):  
Overall Survival ◽  
Clinical Outcome ◽  
Promoter Methylation ◽  
Median Overall Survival ◽  
Methylation Status ◽  
Recurrent Glioblastoma ◽  
Mgmt Promoter Methylation ◽  
Recurrent Tumors ◽  
Mgmt Promoter ◽  
The Relationship

65 Background: Epigenetic sliencing of the MGMT gene promoter in primary glioblastomas of patients subsequently treated with TMZ is associated with prolonged survival. Further, several studies have observed a change in MGMT silencing in paired primary and recurrent glioblastoma. However, the relationship between this “MGMT switch” and patients outcome is largely unknown. Methods: The study involved primary and recurrent tumor tissue samples from 53 glioblastoma patients diagnosed and treated within the First Hospital of Jilin University from January 2003 to November 2010. After surgical treatment, all patients were subjected to radiotherapy with concomitant administration of TMZ. Patients that experienced recurrent tumors received TMZ. 53 patients underwent 58 further operations after recurrence (5 pats received a third surgery). MGMT promoter methylation levels were determined using qMSP. The relationship between “MGMT switch” and clinical outcome was investigated. Results: 53 (M/F=33/20; median age: 49.2±3.6, 19.5-72.3 ys) underwent a first operation for GBM. qMSP analysis revealed MGMT promoter methylation in 19 pats (35.8%, A, OS 31.5 ms); no methylation in 34 pats (64.2%, B, OS 7.9 ms). In the recurrent tumors, MGMT promoter methylation was detected in 25 pats (47.2%); and no methylation in 28 pats (52.8%). Comparison of individual pairs of primary and recurrent GBMs revealed a changed methylation status in 10 (18.9%), including 8 changed from unmethylated to methylated tumors (15.1%, C, OS 29.4 ms), 2 changed from methylated to unmethylated tumors (3.8%, D, OS 10.5 ms). Median overall survival (OS) was 12.1 months. MGMT promoter methylation was significantly associated with a favorable clinical outcome (A vs B, p=0.0027). The outcome of patients were not significant different between group A and group C (p>0.01). Conclusions: The methylation status of the MGMT promoter was altered in 10 (18.9%) of 53 recurrent GBM after chemoradiotherapy. 8 patients the promoter changed from unmethylated to methylated and these patients had a median overall survival similar to the better prognosis of patients who had a methylated promoter in their primary tumor. 2 pats where a change from methylated to unmethylated was observed had a poorer outcome.

Combinational analysis of IDH1/IDH2 mutations, 1p/19q deletions and MGMT promoter methylation for molecular testing of glioma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13152-e13152
Author(s):  
Xiaoni Zhang ◽  
Hongyue Qu ◽  
Qing Yang ◽  
Ziyang Zhu ◽  
Tanxiao Huang ◽  
...  
Keyword(s):  
Promoter Methylation ◽  
Genetic Alterations ◽  
Mgmt Promoter Methylation ◽  
Molecular Testing ◽  
Sequencing Data ◽  
Diagnosis And Prognosis ◽  
Mgmt Promoter ◽  
Ffpe Samples ◽  
Combinational Analysis ◽  
Idh2 Mutation

e13152 Background: Mutations in IDH1 and IDH2, co-deletion of 1p and 19q, and the hyper methylation of the MGMT promoter are the most reported genetic alterations in glioma tumors. Therefore, we designed a study to analyze the prevalence of these biomarkers in glioma, and the correlation of these biomarkers with diagnosis and prognosis. Methods: From September 2018 to January 2019, eighteen patients with primary glioma were prospectively enrolled. For each patient, freshly frozen tissue or FFPE samples were collected. DNA was extracted from these samples and sequenced to at least 5,000× coverage. IDH1/IDH2 mutations and 1p/19q deletions were detected from the sequencing data, whereas MGMT promoter methylation was evaluated by real-time fluorescence qPCR. Results: Of the eighteen patients, 44.4%(8/18) and 33.3%(6/18) harbored IDH1 /IDH2 mutations and 1p/19q deletions, respectively, and 72.2%(13/18) contained MGMT promoter hyper methylation. Within these patients, we found a correlation between IDH1/IDH2 mutation and 1p/19q deletion. Namely, among the 8 patients with a IDH1/IDH2 mutation, 75%(6/8) also contained a 1p/19q deletion, whereas none of the 10 patients with wide-type IDH1/IDH2 displayed the 1p/19q deletion. There was also a correlation between mutations at the loci and MGMT promoter hyper-methylation, specifically, 87.5%(7/8) of the patients with IDH1/IDH2 mutations also exhibited hyper-methylation in MGMT, whereas only hyper-methylation was observed in only 40% (4/10) of IDH1/IDH2 negative patients. Conclusions: From our preliminary result, IDH1/IDH2 mutations may be associated with 1p/19q deletion. To further verify this result, a larger, longitudinal study is ongoing at our institution.

Correlation of the quantitative level of MGMT promoter methylation and overall survival in primary diagnosed glioblastomas using the quantitative MethyQESD method

2019 ◽  
Vol 73 (2) ◽  
pp. 112-115 ◽  
Author(s):  
Charlotte von Rosenstiel ◽  
Benedikt Wiestler ◽  
Bernhard Haller ◽  
Friederike Schmidt-Graf ◽  
Jens Gempt ◽  
...  
Keyword(s):  
Overall Survival ◽  
Promoter Methylation ◽  
Promoter Region ◽  
Dna Methyltransferase ◽  
Methylation Status ◽  
Mgmt Promoter Methylation ◽  
Newly Diagnosed ◽  
Quantitative Level ◽  
Mgmt Promoter ◽  
The Impact

AimsO(6)-methylguanine-DNA-methyltransferase (MGMT) promoter methylation is a high predictive factor for therapy results of temozolomide in patients with glioma. The objective of this work was to analyse the impact of MGMT promoter methylation in patients with primary diagnosed glioblastoma (GBM) relating to survival using a quantitative method (methylation quantification of endonuclease-resistant DNA, MethyQESD) by verifying a cut-off point for MGMT methylation provided by the literature (</≥10%) and calculating an optimal cut-off.Methods67 patients aged 70 years or younger, operated between January 2013 and December 2015, with newly diagnosed IDH wild-type GBM and clinical follow-up were retrospectively investigated in this study. A known MGMT promoter methylation status was the inclusion criteria.ResultsMedian overall survival (OS) was 16.9 months. Patients who had a methylated MGMT promoter region of ≥10% had an improved OS compared with patients with a methylated promoter region of <10% (p=0.002). Optimal cut-off point for MGMT promoter methylation was 11.7% (p=0.012).ConclusionThe results confirm that the quantitative level of MGMT promoter methylation is a positive prognostic factor in newly diagnosed patients with GBM. The cut-off provided by the literature (</≥10%) and the calculated optimal cut-off value of 11.7% give a statistically significant separation. Hence, MethyQESD is a reliable method to calculate MGMT promoter methylation in GBM.

scholarly journals BIOM-02. IDENTIFYING MGMT ALTERATIONS AS BIOMARKERS OF SURVIVAL IN LUNG ADENOCARCINOMA WITH BRAIN METASTASES

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii1-ii1
Author(s):  
Yasin Mamatjan ◽  
Jeffrey Zuccato ◽  
Fabio Moraes ◽  
Michael Cabanero ◽  
Wumairehan Shali ◽  
...  
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Promoter Methylation ◽  
Patient Survival ◽  
Methylation Status ◽  
Mgmt Promoter Methylation ◽  
Mgmt Methylation ◽  
Mgmt Promoter ◽  
Egfr Mutant ◽  
Mgmt Promoter Methylation Status

Abstract EGFR-mutant lung adenocarcinomas (EGFRm-LUAD) have a higher risk of developing brain metastases (BM) compared to non-EGFR-mutant tumors. BM development has significant prognostic impact and leads to poorer patient survival. MGMT promoter methylation is known to determine response to therapy in other cancer types including intracranial gliomas but has not been investigated in EGFRm-LUAD BM. This work aims to assess whether MGMT promoter methylation predicts patient survival or BM development in EGFRm-LUAD patients. A large cohort of 90 primary EGFRm-LUAD tumors, of which 33 (37%) developed BM, were profiled using the Illumina Infinium MethylationEPIC Bead chip. Using the previously reported MGMT-STP27 approach that uses two CpG sites to predict MGMT methylation status, Cox modeling was performed to assess whether MGMT methylation status correlates with overall survival independent of other clinical factors. MGMT methylation significantly predicted poorer survival in EGFRm-LUAD patients that developed BM (p=0.0003) and did not develop BM (p=0.003). A multivariate cox analysis, adjusting for cancer stage and smoking status as potential confounders, showed that MGMT methylation (HR=6.2, 95%CI:2.2–17.4, p=0.0005) and BM development (HR=2.6, 95%CI:1.3–5.3, p=0.007) were both independently predictive of worse overall survival in EGFRm-LUAD patients. This finding of poorer survival in MGMT methylated EGFRm-LUAD is validated in an independent LUAD patient cohort. Total mutation burden, calculated by the number of mutations per megabase of DNA, was substantially higher in MGMT methylated tumours with an interquartile range (IQR) of 58 (30–71) compared to MGMT unmethylated tumours with the IQR of 5.5 (4.3–6.1) resulting p-value of 0.01 for this comparison. Overall, this work shows that MGMT promoter methylation status is an important prognostic biomarker in LUAD patients. MGMT promoter methylation status in EGFRm–LUAD patients with BM may be used to guide patient treatment with potentially a greater extent of treatment for high-risk patients.

scholarly journals CTNI-23. IDH1/2wt ANAPLASTIC GLIOMAS OF THE EORTC RANDOMIZED PHASE III INTERGROUP CATNON TRIAL: OVERALL SURVIVAL RELATED TO TREATMENT, MGMT STATUS AND MOLECULAR FEATURES OF GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii47-ii47
Author(s):  
C Mircea S Tesileanu ◽  
Pim French ◽  
Sarah Erridge ◽  
Michael Vogelbaum ◽  
Anna Nowak ◽  
...  
Keyword(s):  
Overall Survival ◽  
Promoter Methylation ◽  
Mgmt Promoter Methylation ◽  
Phase Iii ◽  
Molecular Characteristics ◽  
Mutation Status ◽  
Molecular Features ◽  
Anaplastic Gliomas ◽  
Mgmt Promoter ◽  
H3f3a Mutation

Abstract BACKGROUND The phase III CATNON trial randomized 751 adult patients with newly diagnosed 1p/19q non-codeleted anaplastic glioma to 59.4 Gy radiotherapy +/- concurrent and/or adjuvant TMZ. Here, we present the molecular analysis of the IDH1/2wt subgroup, and associations between molecular characteristics and patient outcomes. METHODS CNV data and MGMT promoter methylation status were assessed from EPIC methylation array data. IDH1/2 and H3F3A mutation status were determined with a glioma tailored next-generation sequencing panel and TERT promoter mutation status using a SNaPshot assay. Overall survival (OS) was measured from date of randomization. RESULTS Of 654 assessed tumors, 211 (32%) were IDH1/2wt. An H3F3A mutation was present in 14 tumors (K27M: n=10; G34R: n=4). Of the remaining 197 patients, 154 tumors had molecular features of glioblastoma according to cIMPACT-NOW 3 criteria (‘IDH1/2wt astrocytomas WHO IV’), 39 tumors did not (‘IDH1/2wt astrocytomas WHO III’), and 4 had inconclusive molecular data. IDH1/2wt astrocytomas WHO III patients had significantly better survival than WHO IV patients: median OS of 2.83 yrs vs 1.43 yrs respectively [log-rank test: p&lt; 0.001]. Of the 154 IDH1/2wt astrocytoma WHO IV, 55 (36%) were found MGMT promoter methylated. MGMT promoter methylation was prognostic in IDH1/2wt astrocytomas WHO IV patients, with a median OS of 1.86 yrs for methylated vs 1.34 yrs for unmethylated [HR 1.62, p=0.006]. In the IDH1/2wt astrocytomas WHO IV, no effect of concurrent and/or adjuvant TMZ was observed; the HR for OS after RT with any TMZ vs RT alone was 1.31 [95% CI 0.73–2.36, p=0.4] for MGMT promoter methylated and 0.90 [95% CI 0.55–1.45, p=0.7] for unmethylated glioma patients. CONCLUSIONS Our study validated the prognostic value of the cIMPACT-NOW 3 criteria. MGMT promoter methylation is prognostic but not predictive for outcome to TMZ treatment in this cohort of IDH1/2wt anaplastic gliomas with molecular features of glioblastoma.

Promoter methylation of MGMT in paired primary and recurrent glioblastomas.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10543-10543
Author(s):  
Li Bie ◽  
Ji Qing Qiu ◽  
Michael McClelland ◽  
Yan Ju
Keyword(s):  
Overall Survival ◽  
Promoter Methylation ◽  
Median Overall Survival ◽  
Methylation Status ◽  
Mgmt Promoter Methylation ◽  
Mgmt Promoter ◽  
Group A ◽  
Group B ◽  
The Relationship ◽  
Recurrent Gbm

10543 Background: Epigenetic sliencing of MGMT gene promoter in primary glioblastomas (GBM) of pts subsequently treated with temozolomide (TMZ) is associated with prolonged survival. Further, several studies have observed a change in MGMT silencing in paired primary and recurrent GBM. However, the relationship between this “MGMT switch” and patients outcome is largely unknown. Methods: The study involved primary and recurrent tumor tissue samples from 53 GBM pts diagnosed and treated within the First Hospital of Jilin University from Jan 2003 to Nov 2010. After surgical treatment, all pts were subjected to radiotherapy with concomitant administration of TMZ (75 mg/m2/d), followed by 5 cycles of adjuvant TMZ given at 4-weeks intervals. Pts that experienced recurrent tumors received TMZ at a dose of 200 mg/m2/5 days for 4 weeks. 53 pts underwent 58 further operations after recurrence (5 pts received a third surgery). MGMT promoter methylation levels were determined using qMSP. The relationship between “MGMT switch” and clinical outcome was investigated. Results: Fifty three (M/F=33/20; median age: 49.2±3.6, range: 19.5-72.3 ys) underwent a first operation for GBM. qMSP analysis revealed MGMT promoter methylation in 19 pts (35.8%, group A, OS 31.5 ms); no methylation in 34 pts (64.2%, group B, OS 7.9 ms). In the recurrent tumors, MGMT promoter methylation was detected in 25 pts (47.2%); and no methylation in 28 pts (52.8%). Comparison of individual pairs of primary and recurrent GBMs revealed a changed methylation status in 10 (18.9%), including eight changed from unmethylated to methylated tumors (15.1%, group C, OS 29.4 ms), two changed from methylated to unmethylated tumors (3.8%, group D, OS 10.5 ms). Median overall survival was 12.1 ms. MGMT promoter methylation was significantly associated with a favorable clinical outcome (group A vs group B, p=0.0027). The outcome of pts were not significant different between A and C (p>0.01). Conclusions: The methylation status of the MGMT promoter was altered in 10 (18.9%) of 53 recurrent GBM after chemoradiotherapy. Eight pts changed from unmethylated to methylated who have a median overall survival similar to methylated pts. The pts changed from methylated to unmethylated who have poor outcome.

A preliminary comprehensive molecular-based nomogram for individualized estimation of survival in patients with newly diagnosed glioblastoma utilizing global microRNA expression data.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2044-2044
Author(s):  
Denise Fabian ◽  
Erica Hlavin Bell ◽  
Joseph P. McElroy ◽  
Tiantian Cui ◽  
Jessica L. Fleming ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Clinical Data ◽  
Mirna Expression ◽  
Promoter Methylation ◽  
Mgmt Promoter Methylation ◽  
Expression Data ◽  
Newly Diagnosed ◽  
Mgmt Methylation ◽  
Mgmt Promoter

2044 Background: Glioblastoma (GBM) is the most aggressive and common primary brain tumor. Nomograms are prediction models that help form individualized risk scores for cancer patients, which are valuable for treatment decision-making. The aim of this study is to create a refined nomogram by including novel molecular variables beyond MGMT promoter methylation. Methods: Clinical data and miRNA expression data were obtained from 226 newly diagnosed GBM patients. Clinical data included age at diagnosis, sex, Karnofsky performance status (KPS), extent of resection, O6-methylguanine-DNA methyltransferase ( MGMT) promoter methylation status, IDH mutation status and overall survival. Due to low representation of less than 13 cases each, IDH mutant glioblastomas and patients submitted to biopsy-only were excluded. Total RNA was isolated from formalin-fixed paraffin-embedded (FFPE) tissues; miRNA expression was subsequently measured using the NanoString human miRNA v3a assay. A Cox regression model was developed using glmnet R package with the elastic net penalty while adjusting for known prognostic factors. A dichotomized genomic score was created by finding the optimal cutpoint (maximum association with survival) of the linear combination of the selected. A nomogram was generated using known clinical prognostic factors, specifically age, sex, KPS, and MGMT status along with the dichotomized genomic score. Results: Four novel miRNAs were found to significantly correlate with overall survival and were used to create the dichotomized miRNA genomic score (GS). This score split the cohort into a poor performing group (GS_high) and a better performing group (GS_low) (p = 0.0031). A final nomogram was created using the Cox proportional hazards model (Figure 1). Factors that correlated with improved survival included younger age, KPS > 70, MGMT methylation and a low genomic score. Conclusions: This study is a proof of concept demonstrating that integration of molecular variables beyond MGMT methylation improve existing nomograms to provide individualized information about patient prognosis. Future directions include a more comprehensive analysis, including proteomic and methylation data, and subsequent validation in an external cohort. Finally, network analysis integrating molecular signatures of poor performers will help identify therapeutic targets.

scholarly journals Prognostic Implications of Epidermal and Platelet-derived Growth Factor Receptor Alterations in Two Cohorts of IDHwt Glioblastoma

2021 ◽  
Author(s):  
Iyad Alnahhas ◽  
Appaji Rayi ◽  
Maria del Pilar Guillermo Prieto Eibl ◽  
Shirley Ong ◽  
Pierre Giglio ◽  
...  
Keyword(s):  
Promoter Methylation ◽  
Medical Center ◽  
Genetic Alterations ◽  
Mgmt Promoter Methylation ◽  
Response To Treatment ◽  
Cancer Center ◽  
Dismal Prognosis ◽  
Idh Mutations ◽  
Mgmt Promoter ◽  
The Impact

Abstract Background Glioblastoma remains a deadly brain cancer with dismal prognosis. Genetic alterations, including IDH mutations, 1p19q co-deletion status and MGMT promoter methylation have been proven to be prognostic and predictive to response to treatment in gliomas. In this manuscript, we aimed to correlate other mutations and genetic alterations with various clinical endpoints in patients with IDH-wild-type (IDHwt) glioblastoma. Methods We compiled a comprehensive clinically annotated database of IDHwt GBM patients treated at the Ohio State University Wexner Medical Center for whom we had mutational data through a CLIA-certified genomic laboratory. We then added data that is publicly available from Memorial Sloan Kettering Cancer Center through cBioPortal. Each of the genetic alterations (mutations, deletions and amplifications) served as a variable in univariate and multivariate Cox proportional hazard models. Results A total of 175 IDHwt GBM patients with available MGMT promoter methylation data from both cohorts were included in the analysis. As expected, MGMT promoter methylation was significantly associated with improved overall survival (OS). Median OS for MGMT promoter methylated and unmethylated GBM was 26.5 and 18 months, respectively (HR 0.45; p=0.003). Moreover, EGFR/ERBB alterations were associated with favorable outcome (HR of 0.37 (p=0.003), but only in MGMT promoter unmethylated GBM. We further found that patients with EGFR/ERBB alterations who also harbored PDGFRA amplification had a significantly worse outcome (HR 7.89; p=0.025). Conclusions Our data provides further insight into the impact of genetic alterations on various clinical outcomes in IDHwt GBM in two cohorts of patients with detailed clinical information and inspire new therapeutic strategies for IDHwt GBM.

A novel MGMT methylation-based prognostic score in patients with glioblastoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 2048-2048
Author(s):  
Lorenzo Gerratana ◽  
Giuseppe Lombardi ◽  
Elisa De Carlo ◽  
Vanessa Buoro ◽  
Giovanna De Maglio ◽  
...  
Keyword(s):  
Promoter Methylation ◽  
Prognostic Value ◽  
Cox Regression ◽  
Prognostic Score ◽  
Methylation Status ◽  
Mgmt Promoter Methylation ◽  
Quantitative Detection ◽  
Prognostic Impact ◽  
Mutational Status ◽  
Mgmt Promoter

2048 Background: The methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) promoter has been associated with improved outcome in glioblastoma (GBM) patients (pts). Pyrosequencing (PSQ) has been reported to be an accurate method for quantitative detection of CpG islands (CpGs) methylation, but the role of methylation heterogeneity among different CpGs sites is still unclear. Aim of this study was to evaluate on a large multicentric cohort a novel prognostic score based on the evaluation of the MGMT promoter methylation at 10 different CpGs sites. Methods: We retrospectively analyzed a series of 185 pts with GBM treated at the University Hospital of Udine and Istituto Oncologico Veneto in Padua between 2006 and 2015. The methylation level of 10 CpGs (74 – 83) was determined by PSQ. The cut-off point of 9% was used to define a CpG as methylated. One point was assigned to each methylated CpG, with a total score from 0 (all CpGs < 9%) to 10 (all CpGs ≥ 9%). A threshold capable to detect a favorable outcome (Overall Survival, OS > 24 months) has been identified through ROC analysis as 6 by a previous study conducted at our center. The prognostic impact was explored through Cox regression. Results: After a median follow-up of 59 months, the median OS and Progression Free Survival (PFS) in the whole population were 16.41 and 9.67 months, respectively. A score ≥ 6 identified pts with a considerably better median OS (24.85 vs 12.99 months, p < .0001) and PFS (11.44 vs 8.22 months, p < .0001). On multivariate analysis, it remained independently associated with a favorable prognosis (HR 0.38, 95% CI 0.27-0.55, p < 0.0001) after adjustment for IDH1 mutational status (HR 0.42, 95% CI 0.20-0.87, p = .02), age ( > 70 vs ≤ 70 years HR 2.20, 95% CI 1.48-3.28, p = .0001) and ECOG performance status (2-3 vs 0-1 HR 2.35, 95% CI 1.59-3.49, p < .0001). The score’s prognostic value was maintained in all the explored subgroups. Conclusions: Combining methylation data from multiple CpGs increases the prognostic value of the MGMT promoter methylation assessment. The study confirmed the independent prognostic value of a novel score system based on the evaluation of the MGMT promoter methylation at 10 different CpGi sites.

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