The Value of 5-Aminolevulinic Acid in Low-grade Gliomas and High-grade Gliomas Lacking Glioblastoma Imaging Features: An Analysis Based on Fluorescence, Magnetic Resonance Imaging, 18F-Fluoroethyl Tyrosine Positron Emission Tomography, and Tumor Molecular Factors

Neurosurgery. 2016 Mar;78(3):401-11; discussion 411. doi: 10.1227/NEU.0000000000001020.

Abstract

Background: Approximately 20% of grade II and most grade III gliomas fluoresce after 5-aminolevulinic acid (5-ALA) application. Conversely, approximately 30% of nonenhancing gliomas are actually high grade.

Objective: The aim of this study was to identify preoperative factors (ie, age, enhancement, 18F-fluoroethyl tyrosine positron emission tomography [F-FET PET] uptake ratios) for predicting fluorescence in gliomas without typical glioblastomas imaging features and to determine whether fluorescence will allow prediction of tumor grade or molecular characteristics.

Methods: Patients harboring gliomas without typical glioblastoma imaging features were given 5-ALA. Fluorescence was recorded intraoperatively, and biopsy specimens collected from fluorescing tissue. World Health Organization (WHO) grade, Ki-67/MIB-1 index, IDH1 (R132H) mutation status, O-methylguanine DNA methyltransferase (MGMT) promoter methylation status, and 1p/19q co-deletion status were assessed. Predictive factors for fluorescence were derived from preoperative magnetic resonance imaging and F-FET PET. Classification and regression tree analysis and receiver-operating-characteristic curves were generated for defining predictors.

Results: Of 166 tumors, 82 were diagnosed as WHO grade II, 76 as grade III, and 8 as glioblastomas grade IV. Contrast enhancement, tumor volume, and F-FET PET uptake ratio >1.85 predicted fluorescence. Fluorescence correlated with WHO grade (P < .001) and Ki-67/MIB-1 index (P < .001), but not with MGMT promoter methylation status, IDH1 mutation status, or 1p19q co-deletion status. The Ki-67/MIB-1 index in fluorescing grade III gliomas was higher than in nonfluorescing tumors, whereas in fluorescing and nonfluorescing grade II tumors, no differences were noted.

Conclusion: Age, tumor volume, and F-FET PET uptake are factors predicting 5-ALA-induced fluorescence in gliomas without typical glioblastoma imaging features. Fluorescence was associated with an increased Ki-67/MIB-1 index and high-grade pathology. Whether fluorescence in grade II gliomas identifies a subtype with worse prognosis remains to be determined.

MeSH terms

  • Aged
  • Aminolevulinic Acid*
  • Brain Neoplasms / diagnostic imaging*
  • Brain Neoplasms / pathology*
  • Chromosome Deletion
  • Chromosomes, Human, Pair 1 / genetics
  • Female
  • Fluorescence
  • Glioblastoma / diagnostic imaging*
  • Glioblastoma / pathology*
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Neoplasm Grading / methods
  • O(6)-Methylguanine-DNA Methyltransferase / genetics
  • Positron-Emission Tomography / methods
  • Radiopharmaceuticals / pharmacology
  • Tyrosine

Substances

  • Radiopharmaceuticals
  • Tyrosine
  • Aminolevulinic Acid
  • O(6)-Methylguanine-DNA Methyltransferase

Supplementary concepts

  • Chromosome 1, monosomy 1p