(847) 378-0517 or bvd@aans.org
EMBARGOED FOR RELEASE ON APRIL 18
NEW ORLEANS (April 18, 2005) Malignant gliomas, the most common neoplasm in the central nervous system, have a poor prognosis despite the frequent use of a therapeutic combination of surgery, radiotherapy and chemotherapy. Complete surgical removal of these tumors is not possible due to their locally invasive nature within the brain. However, maximal cytoreductive surgery, aimed at removing at least contrast-enhancing tumor seen on magnetic resonance imaging (MRI), is generally considered beneficial. Unfortunately, complete resection of contrast-enhancing regions is only achieved in a small percentage of patients due, in part, to the difficulty of detecting contrast-enhancing tumor margins intraoperatively.
Recently, studies were conducted to determine whether fluorescence-guided resection of malignant gliomas, utilizing five-aminolevulinic acid (5-ALA), might positively impact patients' prognoses and survival rates. The study, Multicentric Phase III Study on Fluorescence-guided Resection of Malignant Gliomas with 5-ALA: Preliminary Results on Interim Analysis of 270 Patients, will be presented by Walter Stummer, MD from 3:30 to 3:45 p.m. on Monday, April 18, 2005, during the 73rd Annual Meeting of the American Association of Neurological Surgeons in New Orleans. Patients were enrolled and randomized by 32 investigators at 18 study centers throughout Germany. The study was sponsored by Medac, in Germany.
Five-aminolevulinic acid leads to the accumulation of fluorescent porphyrins in malignant gliomas, a phenomenon with the potential for enhancing intraoperative identification and resection of these tumors. Porphyrins are strongly fluorescent and can be visualized after appropriate modifications to a standard neurosurgical operating microscope. Patients with suspected malignant gliomas amenable to complete resection of contrast-enhancing tumor were randomized to either fluorescence-guided resection (FL-group) or conventional microsurgery (white light group, WL-group).
In the FL-group, the tumor was resected using fluorescence guidance after 5-ALA (20 mg/kg body weight) had been administered orally three hours prior to induction of anesthesia. In the control arm (WL-group), the tumor was resected as thoroughly as possible using the same microscope and conventional white, xenon illumination. No residual enhancing tumor was found in 65 percent of patients in the ALA group compared to 36 percent in the white light group (p <0.001). Progression-free survival was superior in ALA compared to WL patients (p <0.01), with cumulative 6-months progression-free survival rates of 41 percent and 21 percent, respectively.
When patients were analyzed irrespective of treatment group, based on whether complete removal of tumor was achieved as assessed by early postoperative MRI, complete removal was clearly related to improved survival. Patients without residually enhancing tumor on early postoperative MRI had a significantly longer median survival than patients with residually enhancing tumor on early
postoperative MRI.
"This study addresses the basic controversy in neurosurgery on whether maximal cytoreductive therapy of malignant gliomas is of benefit to patients. In this context, the results demonstrate that fluorescence guidance using 5-ALA enhances resections of malignant gliomas, and that enhanced resections are beneficial by translating into longer progression-free survival," explained Dr. Stummer.
Although the present study was not powered for demonstrating an increase in overall survival, patients in the FL-group had a median survival exceeding patients in the WL-arm: 15.2 vs. 13.5 months. While this difference does not exhibit statistical significance, the crude hazards ratio of 0.81 clearly demonstrated fluorescence-guided resections to be advantageous. The benefit was particularly evident in the laargest subgroup of patients age 55 and older (11.5 vs. 13.8 months).
Founded in 1931 as the Harvey Cushing Society, the American Association of Neurological Surgeons (AANS) is a scientific and educational association with more than 6,800 members worldwide. The AANS is dedicated to advancing the specialty of neurological surgery in order to provide the highest quality of neurosurgical care to the public. All active members of the AANS are certified by the American Board of Neurological Surgery, the Royal College of Physicians and Surgeons (Neurosurgery) of Canada or the Mexican Council of Neurological Surgery, AC. Neurological surgery is the medical specialty concerned with the prevention, diagnosis, treatment and rehabilitation of disorders that affect the entire nervous system, including the spinal column, spinal cord, brain and peripheral nerves.
