Five-aminolevulinic acid for fluorescence-guided resection of recurrent malignant gliomas: a phase ii study

Neurosurgery. 2009 Dec;65(6):1070-6; discussion 1076-7. doi: 10.1227/01.NEU.0000360128.03597.C7.


Objective: To assess the feasibility of 5-aminolevulinic acid (5-ALA) fluorescence guidance for resection of recurrent malignant brain tumors.

Methods: In a multicenter prospective, single-arm, uncontrolled phase II study, 36 patients with recurrent glioma (World Health Organization grade III/IV) received 5-ALA before surgery. After microsurgical resection, biopsies from pathological and nonpathological areas (as identified under conventional white light) were obtained to determine the positive predictive value (PPV) of 5-ALA-induced tissue fluorescence in detecting tumors. Adverse events, neurological examinations, and survival data were documented for a minimal follow-up of 6 months.

Results: The patient-based PPV, defined as the percentage of patients showing positive tumor cell identification in all biopsies taken from areas of weak and strong fluorescence was 97.2% for pathological areas and 79.4% in nonpathological areas. Within areas of strong fluorescence, PPV was higher (91.7%) compared with that of weak fluorescence (82.4%). On the biopsy level for nonpathological-appearing tissue under white light (157 biopsies), the PPV of tissue fluorescence was 93.0% compared with 99.5% in pathological-appearing tissue (197 biopsies). Again, within areas of strong fluorescence, PPV was higher (96.9%) compared with that of weak fluorescence (90.3%). There were no adverse events pertaining to the study drug.

Conclusion: 5-ALA fluorescence has a high predictive value for the detection of tumor in recurrent gliomas. Prior treatment modalities, such as radiation or chemotherapy, do not invalidate the fluorescence guidance with 5-ALA. 5-ALA fluorescence guidance is an effective surgical adjunct in the surgery of recurrent malignant gliomas.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aminolevulinic Acid*
  • Brain Neoplasms / pathology*
  • Brain Neoplasms / surgery
  • Confidence Intervals
  • Female
  • Fluorescence*
  • Follow-Up Studies
  • Glioma / pathology*
  • Glioma / surgery
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Neurologic Examination / methods
  • Neurosurgery / methods
  • Outcome Assessment, Health Care
  • Predictive Value of Tests
  • Prospective Studies
  • Retrospective Studies


  • Aminolevulinic Acid