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Interrelationships between molecular subtype, anatomical location, and extent of resection in diffuse glioma: a systematic review and meta-analysis.

ABSTRACT: AbstractBackgroundThe introduction of the 2016 WHO Classification of Tumors of the Central Nervous System has resulted in tumor groupings with improved prognostic value for diffuse glioma patients. Molecular subtype, primarily based on IDH-mutational status and 1p/19q-status, is a strong predictor of survival. It is unclear to what extent this finding may be mediated by differences in anatomical location and surgical resectability among molecular subgroups. Our aim was to elucidate possible correlations between (1) molecular subtype and anatomical location and (2) molecular subtype and extent of resection.MethodsWe performed a systematic review of literature searching for studies on molecular subtype in relation to anatomical location and extent of resection. Only original data concerning adult participants suffering from cerebral diffuse glioma were included. Studies adopting similar outcomes measures were included in our meta-analysis.ResultsIn the systematic analysis for research questions 1 and 2, totals of 20 and 9 studies were included, respectively. Study findings demonstrated that IDH-mutant tumors were significantly more frequently located in the frontal lobe and less often in the temporal lobe compared with IDH-wildtype gliomas. Within the IDH-mutant group, 1p/19q-codeleted tumors were associated with more frequent frontal and less frequent temporal localization compared with 1p/19q-intact tumors. In IDH-mutant gliomas, greater extent of resection was achieved than in IDH-wildtype tumors.ConclusionsGenetic profile of diffuse cerebral glioma influences their anatomical location and seems to affect tumor resectability.

SUBMITTER: De Leeuw BI

PROVIDER: S-EPMC7212862 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Project description:OBJECTIVE:While the effect of increased extent of resection (EOR) on survival in diffuse infiltrating low-grade glioma (LGG) patients is well established, there is still uncertainty about the influence of the new WHO molecular subtypes. The authors designed a retrospective analysis to assess the interplay between EOR and molecular classes. METHODS:The authors retrospectively reviewed the records of 326 patients treated surgically for hemispheric WHO grade II LGG at Brigham and Women's Hospital and Massachusetts General Hospital (2000-2017). EOR was calculated volumetrically and Cox proportional hazards models were built to assess for predictive factors of overall survival (OS), progression-free survival (PFS), and malignant progression-free survival (MPFS). RESULTS:There were 43 deaths (13.2%; median follow-up 5.4 years) among 326 LGG patients. Median preoperative tumor volume was 31.2 cm3 (IQR 12.9-66.0), and median postoperative residual tumor volume was 5.8 cm3 (IQR 1.1-20.5). On multivariable Cox regression, increasing postoperative volume was associated with worse OS (HR 1.02 per cm3; 95% CI 1.00-1.03; p = 0.016), PFS (HR 1.01 per cm3; 95% CI 1.00-1.02; p = 0.001), and MPFS (HR 1.01 per cm3; 95% CI 1.00-1.02; p = 0.035). This result was more pronounced in the worse prognosis subtypes of IDH-mutant and IDH-wildtype astrocytoma, for which differences in survival manifested in cases with residual tumor volume of only 1 cm3. In oligodendroglioma patients, postoperative residuals impacted survival when exceeding 8 cm3. Other significant predictors of OS were age at diagnosis, IDH-mutant and IDH-wildtype astrocytoma classes, adjuvant radiotherapy, and increasing preoperative volume. CONCLUSIONS:The results corroborate the role of EOR in survival and malignant transformation across all molecular subtypes of diffuse LGG. IDH-mutant and IDH-wildtype astrocytomas are affected even by minimal postoperative residuals and patients could potentially benefit from a more aggressive surgical approach.

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.

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Interrelationships between molecular subtype, anatomical location, and extent of resection in diffuse glioma: a systematic review and meta-analysis.

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