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Original Investigation
November 2016

Association of the Extent of Resection With Survival in GlioblastomaA Systematic Review and Meta-analysis

Author Affiliations
  • 1Department of Medicine, University of Texas Southwestern Medical Center, Dallas
  • 2Ann Barshinger Cancer Center, Lancaster General Health, Lancaster, Pennsylvania
  • 3Department of Neurosurgery, University of Rochester Medical Center, Pittsford, New York
  • 4Department of Neurosurgery, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania
  • 5Department of Medicine, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania
  • 6Department of Neurosurgery, Swedish Cerebrovascular Institute, Seattle, Washington
  • 7Division of Surgery, Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston
JAMA Oncol. 2016;2(11):1460-1469. doi:10.1001/jamaoncol.2016.1373
Key Points

Question  Does increasing the extent of resection improve the likelihood of overall survival in glioblastoma multiforme?

Findings  In this meta-analysis of 37 studies, gross total resection was significantly associated with a lower relative risk for mortality at 1 and 2 years compared with subtotal resection. Overall, a dose-dependent reduction in mortality was seen with increasing extent of resection.

Meaning  These findings support the use of gross total resection for glioblastoma multiforme for reducing 1- and 2-year mortality.

Abstract

Importance  Glioblastoma 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.

Objective  To 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 Sources  Pubmed, 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 Selection  Studies 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 Synthesis  Data 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 Measures  Relative risk (RR) for mortality at 1 and 2 years and progression at 6 months and 1 year.

Results  The 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 Relevance  This 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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