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Survival after hypofractionation in glioblastoma: a systematic review and meta-analysis.

ABSTRACT: BACKGROUND:Glioblastoma multiforme (GBM) has a poor prognosis despite a multi modal treatment that includes normofractionated radiotherapy. So, various hypofractionated alternatives to normofractionated RT have been tested to improve such prognosis. There is need of systematic review and meta-analysis to analyse the literature properly and maybe generalised the use of hypofractionation. The aim of this study was first, to perform a meta-analysis of all controlled trials testing the impact of hypofractionation on survival without age restriction and secondly, to analyse data from all non-comparative trials testing the impact of hypofractionation, radiosurgery and hypofractionated stereotactic RT in first line. MATERIALS/METHODS:We searched Medline, Embase and Cochrane databases to identify all publications testing the impact of hypofractionation in glioblastoma between 1985 and March 2020. Combined hazard ratio from comparative studies was calculated for overall survival. The impact of study design, age and use of adjuvant temozolomide was explored by stratification. Meta-regressions were performed to determine the impact of prognostic factors. RESULTS:2283 publications were identified. Eleven comparative trials were included. No impact on overall survival was evidenced (HR: 1.07, 95%CI: 0.89-1.28) without age restriction. The analysis of non-comparative literature revealed heterogeneous outcomes with limited quality of reporting. Concurrent chemotherapy, completion of surgery, immobilization device, isodose of prescription, and prescribed dose (depending on tumour volume) were poorly described. However, results on survival are encouraging and were correlated with the percentage of resected patients and with patients age but not with median dose. CONCLUSIONS:Because few trials were randomized and because the limited quality of reporting, it is difficult to define the place of hypofactionation in glioblastoma. In first line, hypofractionation resulted in comparable survival outcome with the benefit of a shortened duration. The method used to assess hypofractionation needs to be improved.

SUBMITTER: Trone JC

PROVIDER: S-EPMC7278121 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Survival after hypofractionation in glioblastoma: a systematic review and meta-analysis.

Trone Jane-Chloe JC Vallard Alexis A Sotton Sandrine S Ben Mrad Majed M Jmour Omar O Magné Nicolas N Pommier Benjamin B Laporte Silvy S Ollier Edouard E

Radiation oncology (London, England) 20200608 1

<h4>Background</h4>Glioblastoma multiforme (GBM) has a poor prognosis despite a multi modal treatment that includes normofractionated radiotherapy. So, various hypofractionated alternatives to normofractionated RT have been tested to improve such prognosis. There is need of systematic review and meta-analysis to analyse the literature properly and maybe generalised the use of hypofractionation. The aim of this study was first, to perform a meta-analysis of all controlled trials testing the impac ...[more]

PMID: 32513205

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Project description:ImportanceGlioblastoma multiforme (GBM) remains almost invariably fatal despite optimal surgical and medical therapy. The association between the extent of tumor resection (EOR) and outcome remains undefined, notwithstanding many relevant studies.ObjectiveTo determine whether greater EOR is associated with improved 1- and 2-year overall survival and 6-month and 1-year progression-free survival in patients with GBM.Data sourcesPubmed, CINAHL, and Web of Science (January 1, 1966, to December 1, 2015) were systematically reviewed with librarian guidance. Additional articles were included after consultation with experts and evaluation of bibliographies. Articles were collected from January 15 to December 1, 2015.Study selectionStudies of adult patients with newly diagnosed supratentorial GBM comparing various EOR and presenting objective overall or progression-free survival data were included. Pediatric studies were excluded.Data extraction and synthesisData were extracted from the text of articles or the Kaplan-Meier curves independently by investigators who were blinded to each other's results. Data were analyzed to assess mortality after gross total resection (GTR), subtotal resection (STR), and biopsy. The body of evidence was evaluated according to Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria and PRISMA guidelines.Main outcome and measuresRelative risk (RR) for mortality at 1 and 2 years and progression at 6 months and 1 year.ResultsThe search produced 37 studies suitable for inclusion (41 117 unique patients). The meta-analysis revealed decreased mortality for GTR compared with STR at 1 year (RR, 0.62; 95% CI, 0.56-0.69; P < .001; number needed to treat [NNT], 9) and 2 years (RR, 0.84; 95% CI, 0.79-0.89; P < .001; NNT, 17). The 1-year risk for mortality for STR compared with biopsy was reduced significantly (RR, 0.85; 95% CI, 0.80-0.91; P < .001). The risk for mortality was similarly decreased for any resection compared with biopsy at 1 year (RR, 0.77; 95% CI, 0.71-0.84; P < .001; NNT, 21) and 2 years (RR, 0.94; 95% CI, 0.89-1.00; P = .04; NNT, 593). The likelihood of disease progression was decreased with GTR compared with STR at 6 months (RR, 0.72; 95% CI, 0.48-1.09; P = .12; NNT, 14) and 1 year (RR, 0.66; 95% CI, 0.43-0.99; P < .001; NNT, 26). The quality of the body of evidence by the GRADE criteria was moderate to low.Conclusion and relevanceThis analysis represents the largest systematic review and only quantitative systematic review to date performed on this subject. Compared with STR, GTR substantially improves overall and progression-free survival, but the quality of the supporting evidence is moderate to low.

Project description:BackgroundGlioblastoma (GBM) is a highly aggressive cancer with poor prognosis that needs better treatment modalities. Moreover, there is a lack of reliable biomarkers to predict the response and outcome of current or newly designed therapies. While several molecular markers have been proposed as potential biomarkers for GBM, their uptake into clinical settings is slow and impeded by marker heterogeneity. Detailed assessment of prognostic and predictive value for biomarkers in well-defined clinical trial settings, if available, is scattered throughout the literature. Here we conducted a systematic review and meta-analysis to evaluate the prognostic and predictive significance of clinically relevant molecular biomarkers in GBM patients.Material and methodsA comprehensive literature search was conducted to retrieve publications from 3 databases (Pubmed, Cochrane and Embase) from January 2010 to December 2021, using specific terms. The combined hazard ratios (HR) and confidence intervals (95% CI) were used to evaluate the association of biomarkers with overall survival (OS) in GBM patients.ResultsTwenty-six out of 1831 screened articles were included in this review. Nineteen articles were included in the meta-analyses, and 7 articles were quantitatively summarised. Fourteen studies with 1231 GBM patients showed a significant association of MGMT methylation with better OS with the pooled HR of 1.66 (95% CI 1.32-2.09, p < 0.0001, random effect). Five studies including 541 GBM patients analysed for the prognostic significance of IDH1 mutation showed significantly better OS in patients with IDH1 mutation with a pooled HR of 2.37 (95% CI 1.81-3.12; p < 0.00001]. Meta-analysis performed on 5 studies including 575 GBM patients presenting with either amplification or high expression of EGFR gene did not reveal any prognostic significance with a pooled HR of 1.31 (95% CI 0.96-1.79; p = 0.08).ConclusionsMGMT promoter methylation and IDH1 mutation are significantly associated with better OS in GBM patients. No significant associations were found between EGFR amplification or overexpression with OS.

Project description:Background: The impact of socioeconomic differences on cancer survival has been investigated for several cancer types showing lower cancer survival in patients from lower socioeconomic groups. However, little is known about the relation between the strength of association and the level of adjustment and level of aggregation of the socioeconomic status measure. Here, we conduct the first systematic review and meta-analysis on the association of individual and area-based measures of socioeconomic status with lung cancer survival. Methods: In accordance with PRISMA guidelines, we searched for studies on socioeconomic differences in lung cancer survival in four electronic databases. A study was included if it reported a measure of survival in relation to education, income, occupation, or composite measures (indices). If possible, meta-analyses were conducted for studies reporting on individual and area-based socioeconomic measures. Results: We included 94 studies in the review, of which 23 measured socioeconomic status on an individual level and 71 on an area-based level. Seventeen studies were eligible to be included in the meta-analyses. The meta-analyses revealed a poorer prognosis for patients with low individual income (pooled hazard ratio: 1.13, 95 % confidence interval: 1.08-1.19, reference: high income), but not for individual education. Group comparisons for hazard ratios of area-based studies indicated a poorer prognosis for lower socioeconomic groups, irrespective of the socioeconomic measure. In most studies, reported 1-, 3-, and 5-year survival rates across socioeconomic status groups showed decreasing rates with decreasing socioeconomic status for both individual and area-based measures. We cannot confirm a consistent relationship between level of aggregation and effect size, however, comparability across studies was hampered by heterogeneous reporting of socioeconomic status and survival measures. Only eight studies considered smoking status in the analysis. Conclusions: Our findings suggest a weak positive association between individual income and lung cancer survival. Studies reporting on socioeconomic differences in lung cancer survival should consider including smoking status of the patients in their analysis and to stratify by relevant prognostic factors to further explore the reasons for socioeconomic differences. A common definition for socioeconomic status measures is desirable to further enhance comparisons between nations and across different levels of aggregation.

Dataset Information

Survival after hypofractionation in glioblastoma: a systematic review and meta-analysis.

Publications

Survival after hypofractionation in glioblastoma: a systematic review and meta-analysis.

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