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


CONCLUSIONS
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.
Nabavi
Arya
A
Department of Neurosurgery, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Thurm
Holger
H
Zountsas
Basilios
B
Pietsch
Thorsten
T
Lanfermann
Heinrich
H
Pichlmeier
Uwe
U
Mehdorn
Maximilian
M
D000328:Adult; D000368:Aged; D000622:Aminolevulinic Acid; D001932:Brain Neoplasms / Q000473:pathology* / Q000601:surgery; D016001:Confidence Intervals; D005260:Female; D005453:Fluorescence; D005500:Follow-Up Studies; D005910:Glioma / Q000473:pathology* / Q000601:surgery; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination / Q000379:methods; D009493:Neurosurgery / Q000379:methods; D017063:Outcome Assessment, Health Care; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012189:Retrospective Studies
D000622:Aminolevulinic Acid