Fluorescence-guided resection of glioblastoma multiforme by using 5-aminolevulinic acid-induced porphyrins: a prospective study in 52 consecutive patients.
OBJECTIVE
It has been established that 5-aminolevulinic acid (5-ALA) induces the accumulation of fluorescent porphyrins in glioblastoma multiforme (GBM), a phenomenon potentially exploitable to guide tumor resection. In this study the authors analyze the influence of fluorescence-guided resection on postoperative magnetic resonance (MR) imaging and survival in a series of patients who underwent surgery in the authors' department.


METHODS
Fifty-two consecutive patients with GBM received oral doses of 5-ALA (20 mg/kg body weight) 3 hours before induction of anesthesia. Intraoperatively, tumor fluorescence was visualized using a modified operating microscope. Fluorescing tissue was removed whenever it was considered safely possible. Residual enhancement on early postoperative MR imaging was quantified and related to each patient's characteristics to determine which factors influenced resection. Survival was analyzed using the Kaplan-Meier method and multivariate analysis was performed in which the Karnofsky Performance Scale (KPS) score, residual fluorescence, patient age, and residual enhancement on MR images were considered. Intraoperatively, two fluorescence qualities were perceived: solid fluorescence generally reflected coalescent tumor, whereas vague fluorescence mostly corresponded to infiltrative tumor. Complete resection of contrast-enhancing tumor was accomplished in 33 patients (63%). Residual intraoperative tissue fluorescence left unresected for safety reasons predicted residual enhancement on MR images in 18 of the 19 remaining patients. Age, residual solid fluorescence, and absence of contrast enhancement in MR imaging were independent explanatory factors for survival, whereas the KPS score was significant only in univariate analysis. No perioperative deaths and one case of permanent morbidity were encountered.


CONCLUSIONS
The observations in this study indicate the usefulness of 5-ALA-induced tumor fluorescence for guiding tumor resection. The completeness of resection, as determined intraoperatively from residual tissue fluorescence, was related to postoperative MR imaging findings and to survival in patients suffering from GBM.
Stummer
W
W
Department of Neurosurgery, Institute for Neuropathology, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany. wstummer@nc.med.uni-muenchen.de
Novotny
A
A
Stepp
H
H
Goetz
C
C
Bise
K
K
Reulen
H J
HJ
D000328:Adult; D000368:Aged; D000622:Aminolevulinic Acid; D001921:Brain / Q000473:pathology / Q000601:surgery; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D005260:Female; D005453:Fluorescence; D005909:Glioblastoma / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011166:Porphyrins / Q000378:metabolism*; D011446:Prospective Studies; D015996:Survival Rate
D011166:Porphyrins; D000622:Aminolevulinic Acid