title: Surgery for Glioblastoma: Impact of the Combined Use of 5-Aminolevulinic Acid and Intraoperative MRI on Extent of Resection and Survival.
abstract: BACKGROUND
  There is rising evidence that in glioblastoma (GBM) surgery an increase of extent of resection (EoR) leads to an increase of patient's survival. Based on histopathological assessments tumor depiction of Gd-DTPA enhancement and 5-aminolevulinic-acid-fluorescence (5-ALA) might be synergistic for intraoperative resection control.
  
  
  OBJECTIVE
  To assess impact of additional use of 5-ALA in intraoperative MRI (iMRI) assisted surgery of GBMs on extent of resection (EoR), progression free survival (PFS) and overall survival (OS).
  
  
  METHODS
  We prospectively enrolled 33 patients with GBMs eligible for gross-total-resection(GTR) and performed a combined approach using 5-ALA and iMRI. As a control group, we performed a retrospective matched pair assessment, based on 144 patients with iMRI-assisted surgery. Matching criteria were, MGMT promotor methylation, recurrent surgery, eloquent location, tumor size and age. Only patients with an intended GTR and primary GBMs were included. We calculated Kaplan Mayer estimates to compare OS and PFS using the Log-Rank-Test. We used the T-test to compare volumetric results of EoR and the Chi-Square-Test to compare new permanent neurological deficits (nPND) and general complications between the two groups.
  
  
  RESULTS
  Median follow up was 31 months. No significant differences between both groups were found concerning the matching criteria. GTR was achieved significantly more often (p <0.010) using 5-ALA&iMRI (100%) compared to iMRI alone (82%). Mean EoR was significantly (p<0.004) higher in 5-ALA&iMRI-group (99.7%) than in iMRI-alone-group (97.4%) Rate of complications did not differ significantly between groups (21% iMRI-group, 27%5-ALA&iMRI-group, p<0.518). nPND were found in 6% in both groups. Median PFS (6 mo resp.; p<0.309) and median OS (iMRI:17 mo; 5-ALA&iMRI-group: 18 mo; p<0.708)) were not significantly different between both groups.
  
  
  CONCLUSIONS
  We found a significant increase of EoR when combining 5-ALA&iMRI compared to use of iMRI alone. Maximizing EoR did not lead to an increase of complications or neurological deficits if used with neurophysiological monitoring in eloquent lesions. No final conclusion can be drawn whether a further increase of EoR benefits patient's progression free survival and overall survival.
authors.affiliation: Department of Neurosurgery, Campus Günzburg, University of Ulm, Ludwig Heilmeyerstr. 2, Günzburg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Coburger
authors.affiliation: Department of Neurosurgery, Campus Günzburg, University of Ulm, Ludwig Heilmeyerstr. 2, Günzburg, Germany.
authors.forename: Vincent
authors.initials: V
authors.lastname: Hagel
authors.affiliation: Department of Neurosurgery, Campus Günzburg, University of Ulm, Ludwig Heilmeyerstr. 2, Günzburg, Germany.
authors.forename: Christian Rainer
authors.initials: CR
authors.lastname: Wirtz
authors.affiliation: Department of Neurosurgery, Campus Günzburg, University of Ulm, Ludwig Heilmeyerstr. 2, Günzburg, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: König
mesh_terms: D000328:Adult; D000368:Aged; D000622:Aminolevulinic Acid; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D016022:Case-Control Studies; D005909:Glioblastoma / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008875:Middle Aged; D016343:Monitoring, Intraoperative / Q000379:methods*; D018365:Neoplasm, Residual; D061848:Optical Imaging / Q000379:methods*; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000622:Aminolevulinic Acid