scholarly journals MGMT promoter methylation testing to predict overall survival in people with glioblastoma treated with temozolomide: a comprehensive meta-analysis based on a Cochrane Review

2021 ◽  
Author(s):  
Sebastian Brandner ◽  
Alexandra McAleenan ◽  
Claire Kelly ◽  
Francesca Spiga ◽  
Hung-Yuan Cheng ◽  
...  
Keyword(s):  
Overall Survival ◽  
Dna Methyltransferase ◽  
Meta Analysis ◽  
Alkylating Agents ◽  
Cochrane Review ◽  
Predictive Biomarker ◽  
Test Method ◽  
Sufficient Information ◽  
Cpg Sites ◽  
Hazard Ratios

Abstract BACKGROUND The DNA repair protein O6 methylguanine-DNA methyltransferase (MGMT) causes resistance of tumour cells to alkylating agents. It is a predictive biomarker in high grade gliomas treated with temozolomide, however there is no consensus on which test method, methylation sites, and cut-off values to use. METHODS We performed a Cochrane Review to examine studies using different techniques to measure MGMT and predict survival in glioblastoma patients treated with temozolomide. Eligible longitudinal studies included adults with glioblastoma treated with temozolomide with or without radiotherapy, or surgery; where MGMT status was determined in tumour tissue, and assessed by one or more technique; and where overall survival was an outcome parameter, with sufficient information to estimate hazard ratios. Two or more methods were compared in 32 independent cohorts with 3474 patients. RESULTS Methylation-specific PCR (MSP) and pyrosequencing (PSQ) techniques were more prognostic than immunohistochemistry for MGMT protein, and PSQ is a slightly better predictor than MSP. CONCLUSIONS We cannot draw strong conclusions about use of frozen tissue versus formalin-fixed paraffin embedded in MSP and PSQ. Also, our meta-analysis does not provide strong evidence about the best CpG sites or threshold. MSP has been studied mainly for CpG sites 76-80 and 84-87 and Pyrosequencing at CpG sites ranging from 72 to 95. A cut-off threshold of 9% for CpG sites 74-78 performed better than higher thresholds of 28% or 29% in two of three good-quality studies. 190 studies were identified presenting hazard ratios from survival analysis in patients in which MGMT methylation was measured by one technique only.

scholarly journals HOTAIR as a Prognostic Predictor for Diverse Human Cancers: A Meta- and Bioinformatics Analysis

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 778 ◽  
Author(s):  
Halil Ibrahim Toy ◽  
Didem Okmen ◽  
Panagiota I. Kontou ◽  
Alexandros G. Georgakilas ◽  
Athanasia Pavlopoulou
Keyword(s):  
Overall Survival ◽  
Cancer Patients ◽  
Bioinformatics Analysis ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Free Survival ◽  
Human Cancers ◽  
Potential Biomarker

Several studies suggest that upregulated expression of the long non-coding RNA HOX transcript antisense RNA (HOTAIR) is a negative predictive biomarker for numerous cancers. Herein, we performed a meta-analysis to further investigate the prognostic value of HOTAIR expression in diverse human cancers. To this end, a systematic literature review was conducted in order to select scientific studies relevant to the association between HOTAIR expression and clinical outcomes, including overall survival (OS), recurrence-free survival (RFS)/disease-free survival (DFS), and progression-free survival (PFS)/metastasis-free survival (MFS) of cancer patients. Collectively, 53 eligible studies including a total of 4873 patients were enrolled in the current meta-analysis. Pooled hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) were calculated to assess the relationship between HOTAIR and cancer patients’ survival. Elevated HOTAIR expression was found to be significantly associated with OS, RFS/DFS and PFS/MFS in diverse types of cancers. These findings were also corroborated by the results of bioinformatics analysis on overall survival. Therefore, based on our findings, HOTAIR could serve as a potential biomarker for the prediction of cancer patient survival in many different types of human cancers.

scholarly journals Long non-coding RNA XIST predicts worse prognosis in digestive system tumors: a systemic review and meta-analysis

2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Xuefang Liu ◽  
Xinliang Ming ◽  
Wei Jing ◽  
Ping Luo ◽  
Nandi Li ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cancer Patients ◽  
Digestive System ◽  
Meta Analysis ◽  
Predictive Biomarker ◽  
Systemic Review ◽  
Cochrane Library ◽  
Expression Levels ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Increasing studies are indicating that long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) is associated with the prognosis of cancer patients. However, the results have been disputed. Therefore, we aimed to further explore the prognostic value and clinical significance of XIST in various types of cancers. Then, we focussed our research on the comparison of the predictive value of XIST between digestive system tumors and non-digestive system tumors. We performed a systematic search by looking up PubMed, Embase, Cochrane Library, Web of Science, and Medline (up to 3 January 2018). Fifteen studies which matched our inclusion criteria with a total of 920 patients for overall survival and 867 patients for clinicopathological characteristics were included in this meta-analysis. Pooled hazard ratios (HR) and odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs) were calculated to summarize the effects. Our results suggested that high expression levels of XIST were associated with unfavorable overall survival in cancer patients (pooled HR = 1.81, 95% CI: 1.45–2.26). Additionally, we found that XIST was more valuable in digestive system tumors (pooled HR = 2.24, 95% CI: 1.73–2.92) than in non-digestive system tumors (pooled HR = 1.22, 95% CI: 0.60–2.45). Furthermore, elevated expression levels of XIST were connected with distant metastasis and tumor stage. XIST was correlated with poor prognosis, which suggested that XIST might serve as a novel predictive biomarker for cancer patients, especially for patients of digestive system tumors.

Surgery and adjuvant chemotherapy (CT) compared to surgery alone in non-small cell lung cancer (NSCLC): A meta-analysis using individual patient data (IPD) from randomized clinical trials (RCT)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7552-7552 ◽  
Author(s):  
L. A. Stewart ◽  
S. Burdett ◽  
J. F. Tierney ◽  
J. Pignon
Keyword(s):  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Alkylating Agents ◽  
Distant Recurrence ◽  
Rank Test ◽  
Patient Subgroup ◽  
Resected Nsclc ◽  
Hazard Ratios ◽  
Future Policy ◽  
Treatment Comparisons

7552 Background: A previous IPD meta-analysis (BMJ 1995;311:899) that suggested CT may have a role in the treatment of NSCLC has been updated. This includes RCTs, regimens and outcomes that were not available in 1995. The meta-analysis examines the role of CT in 7 treatment comparisons. Here we report on the effectiveness of surgery plus adjuvant CT compared with surgery alone. Methods: We conducted a systematic search for RCTs followed by the central collection, checking and re-analysis of updated IPD. Results from RCTs were combined using the stratified (by trial) log rank test to calculate individual and pooled hazard ratios (HRs). Previously included RCTs using long-term alkylating agents were excluded from this analysis due to their antiquity. Results: IPD were obtained on 8147 patients from 30 RCTs. 15 RCTs used a cisplatin combination without Tegafur/Tegafur+Uracil (UFT), 8 RCTs used Tegafur/UFT without cisplatin and 7 RCTs used Tegafur/UFT and cisplatin. This represents 95% of all known randomised patients and adds 18 trials and 5835 patients to the 1995 analyses. The results show a highly significant benefit of CT on survival (HR=0.86 95% CI 0.81–0.93, p<0.000001), with an absolute benefit of 4% (from 60% to 64%) at 5 years. Results were similar for recurrence-free survival and time to distant recurrence, but there was a larger effect on time to local recurrence ( Table ). There was no clear difference in effect by type of CT given. There was no clear evidence that any patient subgroup defined by age, sex or histology benefited more or less from CT. There was a suggestion of a trend in effect by stage (p=0.047), this will be explored further. Conclusion: The results demonstrate conclusively and consistently a benefit of adjuvant CT in resected NSCLC, irrespective of the regimen used, the patient subgroup treated or the endpoint assessed, thus providing reliable estimates on which to base future policy and research. [Table: see text] [Table: see text]

scholarly journals Impact of Physical Activity on Cancer-Specific and Overall Survival of Patients with Colorectal Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Gaetan Des Guetz ◽  
Bernard Uzzan ◽  
Thierry Bouillet ◽  
Patrick Nicolas ◽  
Kader Chouahnia ◽  
...  
Keyword(s):  
Physical Activity ◽  
Colorectal Cancer ◽  
Overall Survival ◽  
Meta Analysis ◽  
Fixed Effect Model ◽  
Cochrane Library ◽  
Hazard Ratios ◽  
Effect Model ◽  
Keywords Colorectal Cancer ◽  
The Cochrane Library

Background. Physical activity (PA) reduces incidence of colorectal cancer (CRC). Its influence on cancer-specific (CSS) and overall survival (OS) is controversial.Methods. We performed a literature-based meta-analysis (MA) of observational studies, using keywords “colorectal cancer, physical activity, and survival” in PubMed and EMBASE. No dedicated MA was found in the Cochrane Library. References were cross-checked. Pre- and postdiagnosis PA levels were assessed by MET. Usually, “high” PA was higher than 17 MET hour/week. Hazard ratios (HRs) for OS and CSS were calculated, with their 95% confidence interval. We used more conservative adjusted HRs, since variables of adjustment were similar between studies. When higher PA was associated with improved survival, HRs for detrimental events were set to <1. We used EasyMA software and fixed effect model whenever possible.Results. Seven studies (8056 participants) were included, representing 3762 men and 4256 women, 5210 colon and 1745 rectum cancers. Mean age was 67 years. HR CSS for postdiagnosis PA (higher PA versus lower) was 0.61 (0.44–0.86). The corresponding HR OS was 0.62 (0.54–0.71). HR CSS for prediagnosis PA was 0.75 (0.62–0.91). The corresponding HR OS was 0.74 (0.62–0.89).Conclusion. Higher PA predicted a better CSS. Sustained PA should be advised for CRC. OS also improved (reduced cardiovascular risk).

scholarly journals The Value of PD-L1 Expression as Predictive Biomarker in Metastatic Renal Cell Carcinoma Patients: A Meta-Analysis of Randomized Clinical Trials

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1945 ◽  
Author(s):  
Alberto Carretero-González ◽  
David Lora ◽  
Isabel Martín Sobrino ◽  
Irene Sáez Sanz ◽  
María T. Bourlon ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Clinical Trials ◽  
Renal Cell ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Standard Of Care ◽  
Predictive Biomarker ◽  
P Value ◽  
Metastatic Rcc

Immune checkpoint inhibitors (ICIs) are soluble antibodies that have dramatically changed the outcomes including overall survival in a subset of kidney tumors, specifically in renal cell carcinoma (RCC). To date, there is no a single predictive biomarker approved to be used to select the patients that achieve benefit from ICIs targeting. It seems reasonable to analyze whether the programmed death-ligand 1 (PD-L1) expression could be useful. To assess the role of PD-L1 expression as a potential predictive biomarker for benefit of ICIs in RCC patients, we performed a search of randomized clinical trials (RCTs) comparing ICIs (monotherapy or in combination with other therapies) to standard of care in metastatic RCC patients according to PRISMA guidelines. Trials must have included subgroup analyses evaluating the selected outcomes (progression-free survival (PFS) and overall survival (OS)) in different subsets of patients according to PD-L1 expression on tumor samples. Hazard ratios with confidence intervals were used as the measure of efficacy between groups. A total of 4635 patients (six studies) were included (ICIs arm: 2367 patients; standard of care arm: 2268 patients). Globally, PFS and OS results favored ICIs. Differential expression of PD-L1 on tumor samples could select a subset of patients who could benefit more in terms of PFS (those with higher levels; p-value for difference between subgroups: <0.0001) but it did not seem to impact in OS results (p-value for difference: 0.63). As different methods to assess PD-L1 positivity were used among trials, this heterogeneity could have an influence on the results. PD-L1 could represent a biomarker to test PFS in clinical trials but its value for OS is less clear. In this meta-analysis, the usefulness of PD-L1 expression as a predictive biomarker to select treatment in metastatic RCC patients was not clearly shown.

scholarly journals PATH-04. INFLUENCE OF INDIVIDUAL CpG METHYLATION STATUS OF THE MGMT PROMOTOR ON OUTCOME IN ADULT PATIENTS WITH GLIOBLASTOMA MULTIFORME RECEIVING ALKYLATING AGENT TREATMENT

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi143-vi143
Author(s):  
Sebastian Siller ◽  
Michael Lauseker ◽  
Armin Giese ◽  
Joerg-Christian Tonn ◽  
Karim-Maximilian Niyazi ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Mrna Expression ◽  
Dna Methyltransferase ◽  
Alkylating Agents ◽  
Methylation Status ◽  
Tumor Resection ◽  
Cpg Sites ◽  
Cpg Site ◽  
Promotor Region ◽  
The Individual

Abstract BACKGROUND Methylation of O-6-methylguanine-DNA-methyltransferase (MGMT) promotor causes gene silencing and has been associated with a favourable prognosis in patients with glioblastoma multiforme (GBM) receiving alkylating chemotherapy. However, analysis of MGMT promotor methylation is usually reported as a cut-off depending on the results of the correspondent CpG-site testing. This approach disregards a possible heterogeneity concerning the methylation status within the individual CpG-sites and its possible association with prognosis in GBM patients. The current study aimed at elucidating the association between methylation of CpG-sites 74–98 within the MGMT promotor region and outcome in GBM patients receiving alkylating agents. METHODS Individual methylation status of 230 patients with histologically proven GBM following concomitant radio-chemotherapy with TMZ after stereotactic biopsy or open tumor resection was assessed by the Sanger-sequencing approach. Methylation of CpG-sites 74–98 within the MGMT promotor region was defined according to a ratio of cytosine/thymine peak > 50%. The total number of methylated CpG-sites was correlated with outcome using proportional hazards models. In a subset of 34 patients, a correlation between individual CpG-site methylation and MGMT mRNA-expression was performed. RESULTS Median progression-free (PFS) and overall survival (OS) were 7.8 and 14.6months, respectively. The cumulative total number of methylated loci within the CpG-sites 74–98 was strongly associated with both PFS and OS and retained its prognostic influence on outcome in multivariate models (p< 0.001). Furthermore, a linear coherence between the total number of methylated CpG-sites 74–98 and survival parameters could be observed. Moreover, low number of methylated CpG-sites was observed in tumor specimen with a high mRNA-expression and vice versa (Spearman-correlation-coefficient: -0.62). CONCLUSION Our data suggest a strong linear coherence between outcome and the total number of methylated CpG-sites 74–98, thus an up-front analysis of the individual GpC-site methylation status prior to initiation of alkylating chemotherapy might help improving treatment response in GBM patients.

scholarly journals PATH-28. EXTENT AND PROGNOSTIC VALUE OF MGMT PROMOTOR METHYLATION DEPEND ON IDH MUTATION AND 1p19q CO-DELETION IN GLIOMA WHO GRADE II

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii170-ii170
Author(s):  
Philipp Karschnia ◽  
Nico Teske ◽  
Sebastian Siller ◽  
Mario M Dorostkar ◽  
Jonathan Weller ◽  
...  
Keyword(s):  
Overall Survival ◽  
Dna Methyltransferase ◽  
Methylation Status ◽  
Malignant Progression ◽  
Wild Type ◽  
Who Grade ◽  
Cpg Sites ◽  
Idh Mutations ◽  
Promotor Region ◽  
Grade Ii

Abstract INTRODUCTION Methylation of the promotor region of the O6-methylguanin-DNA-methyltransferase (MGMT) gene is associated with increased survival in low- and high-grade glioma. It is unknown whether this association also applies to the 2016 WHO categories of glioma WHO grade II. MATERIAL AND METHODS We retrospectively searched the institutional database of the Center for Neuro-Oncology for patients with glioma WHO grade II. Patients were assigned to one of three groups according to the 2016 WHO classification system: 1. 1p19q co-deleted oligodendroglioma, IDH mutant; 2. 1p19q non-codeleted astrocytoma, IDH mutant; 3. 1p19q non-codeleted astrocytoma, IDH wild-type. MGMT methylation status was analysed using Sanger sequencing of the CpG sites 74-98 within the MGMT promotor region. The total number of methylated CpG sites was calculated for each patient. RESULTS 155 patients with glioma WHO grade II were encountered, including 81 1p19q co-deleted, IDH mutant oligodendrogliomas; 54 IDH mutant astrocytomas; and 20 IDH wild-type astrocytomas. The mean number of methylated CpG sites among oligodendrogliomas was significantly higher when compared to IDH mutant astrocytomas (18.9 ± 0.4 vs. 16.3 ± 0.6; p = 0.001). In turn, the number of methylated CpG sites among IDH mutant astrocytomas was higher when compared to IDH wild-type astrocytomas (16.3 ± 0.6 vs. 12.3 ± 1.9; p = 0.007). Median follow-up was estimated at 35 months. Median time to malignant progression was 87 months for all patients, and median overall survival was not reached. In the entire cohort, a larger number of methylated CpG sites was prognostic of overall survival and time to malignant progression. When analysed separately for the three WHO subgroups, a similar association was only retained in IDH wild-type astrocytoma. CONCLUSION In our series of WHO II gliomas, MGMT promotor methylation appeared strongly associated with 1p19q codeletion and IDH mutations. MGMT promotor methylation was only prognostic in IDH wild-type astrocytoma.

scholarly journals Adjuvant Systemic Therapy after Chemoradiation and Brachytherapy for Locally Advanced Cervical Cancer: A Systematic Review and Meta-Analysis

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1880
Author(s):  
Nanda Horeweg ◽  
Prachi Mittal ◽  
Patrycja L. Gradowska ◽  
Ingrid Boere ◽  
Supriya Chopra ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cervical Cancer ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Treatment Completion ◽  
Advanced Cervical Cancer ◽  
Locally Advanced Cervical Cancer ◽  
Hazard Ratios

Background: Standard of care for locally advanced cervical cancer is chemoradiation and brachytherapy. The addition of adjuvant systemic treatment may improve overall survival. A systematic review and meta-analysis was conducted to summarize evidence on survival outcomes, treatment completion and toxicity. Methods: PubMed, EMBASE and Web of Science were systematically searched for relevant prospective and retrospective studies. Two authors independently selected studies, extracted data and assessed study quality. Pooled hazard ratios for survival endpoints were estimated using random effect models. Weighted averages of treatment completion and toxicity rates were calculated and compared by the Fisher exact test. Results: The search returned 612 articles; 35 articles reporting on 29 different studies on adjuvant chemotherapy or immunotherapy were selected for systematic review. Twelve studies on an adjuvant platinum–pyrimidine antagonist or platinum–taxane were included for meta-analysis. The pooled hazard ratios for overall survival were 0.76 (99%CI: 0.43–1.34, p = 0.22) and 0.47 (99%CI: 0.12–1.86, p = 0.16) for the addition of, respectively, a platinum–pyrimidine antagonist or platinum–taxane to chemoradiation and brachytherapy. Completion rates were 82% (95%CI: 76–87%) for platinum–pyrimidine antagonist and 74% (95%CI: 63–85%) for platinum–taxane. Severe acute hematological and gastro-intestinal toxicities were significantly increased by adding adjuvant chemotherapy to chemoradiation and brachytherapy. Conclusions: The addition of adjuvant platinum–pyrimidine antagonist or platinum–taxane after chemoradiation and brachytherapy does not significantly improve overall survival, while acute toxicity is significantly increased. These adjuvant treatment strategies can therefore not be recommended for unselected patients with locally advanced cervical cancer.

scholarly journals Statin use and the overall survival of renal cell carcinoma: A meta-analysis

2020 ◽  
Vol 43 (4) ◽  
pp. E17-23
Author(s):  
Ping Wu ◽  
Tingting Xiang ◽  
Jing Wang ◽  
Run Lv ◽  
Yimeng Zhuang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Meta Analysis ◽  
Cochrane Review ◽  
Cochrane Library ◽  
Control Group ◽  
China National Knowledge Infrastructure ◽  
Statin Use

Purpose: Statins are commonly prescribed drugs that reduce cholesterol levels and the risk of cardiovascular and cerebrovascular events. Clinical studies have shown that statins also possess cancer-preventive properties. Two studies have reported that statins also possess cancer-preventive properties; however, whether statins improve the prognosis of patients with renal cell carcinoma is still unclear. In this study, we used meta-analysis to evaluate the association between statin use and overall survival risk in patients with renal cell carcinoma. Methods: Published studies on statin-treated renal cell carcinoma were retrieved from PubMed, Embase, The Cochrane Library, China National Knowledge Infrastructure and Wanfang databases from inception to July 2019. The relevant data were extracted and a meta-analysis was performed using Cochrane Review Manager (RevMan 5.3) software. Results: Data from five studies, which reported on 5,299 patients, were analysed. The application of statins showed no effects on the overall survival of patients with renal cell carcinoma compared with the control group (OR = 1.07, 95% CI:0.77 to 1.49, P = 0.68). Conclusions: The findings of this meta-analysis suggest that statin application does not affect the overall survival of patients with renal cell carcinoma.

scholarly journals Meta-analytic evaluation of the correlation between event-free survival and overall survival in randomized controlled trials of newly diagnosed Ewing sarcoma.

2020 ◽  
Author(s):  
Kazuhiro Tanaka ◽  
Masanori Kawano ◽  
Tatsuya Iwasaki ◽  
Ichiro Itonaga ◽  
Hiroshi Tsumura
Keyword(s):  
Overall Survival ◽  
Randomized Controlled Trials ◽  
Ewing Sarcoma ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Newly Diagnosed ◽  
Event Free Survival ◽  
Free Survival ◽  
Randomized Controlled ◽  
Hazard Ratios

Abstract Background In randomized controlled trials (RCTs) of adjuvant treatment for malignant tumors, event-free survival (EFS) is considered the most acceptable surrogate for overall survival (OS). However, even though EFS has repeatedly been selected as a primary endpoint in RCTs of Ewing sarcoma (ES), the surrogacy of EFS for OS has not been investigated. This study aimed to evaluate the surrogacy of EFS for OS in RCTs of chemotherapy for newly diagnosed ES using a meta-analytic approach. Methods We identified seven RCTs of newly diagnosed ES through a systematic review, and a meta-analysis was performed to evaluate the efficacy and adverse events associated with chemotherapy for previously untreated ES. The correlation between EFS and OS was investigated using weighted linear regression analysis and Spearman rank correlation coefficients (ρ). The strength of the correlation was evaluated using the coefficient of determination (R2). Results A total of 3,612 patients were randomly assigned to 17 treatment arms in the eligible RCTs. The meta-analysis revealed that the hazard ratios for OS and EFS showed significantly better results in the experimental treatment groups with increasing toxicities. The correlation between the hazard ratios for EFS and OS was good (R2 = 0.747, ρ = 0.683), and the correlation tended to be more favorable in cases of localized ES (R2 = 0.818, ρ = 0.929). Conclusions Overall, the trial-level correlation between EFS and OS was good for newly diagnosed ES and was very good in cases of localized disease. EFS may be useful as a surrogate endpoint in RCTs of ES, and the surrogacy of EFS is worth verifying using individual data.

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