Daniel M. Keller, PhD

April 20, 2011

April 20, 2011 (Denver, Colorado) — Repeat Gamma Knife stereotactic radiosurgery (GKSR) safely and effectively obliterates arteriovenous malformations (AVMs) if a first radiosurgery failed to eliminate the problem, researchers at the University of Pittsburgh in Pennsylvania announced here at the American Association of Neurological Surgeons (AANS) 79th Annual Meeting. AVMs have about a 4% risk for hemorrhage per year, with a 15% to 20% risk for stroke or death when they bleed. In successfully treated cases, the risk for hemorrhage and death decreases over time as the AVM disappears.

Between 1987 and 2006, 996 patients with AVMs underwent GKSR, and repeat GKSR was performed on 105 patients (53 men and 52 women) with incompletely obliterated AVMs. Patients had a median age of 31 years (range, 2-66 years) at the time of the initial treatment, The repeat procedure was performed at a median of 40.9 months after the first one (range, 27.5-139 months), and the median margin dose at the initial and repeat procedure was 18 Gy.

Hideyuki Kano, MD, PhD, research assistant professor of neurological surgery at the University of Pittsburgh, reported that the median AVM target volume at the initial procedure was 6.4 cm3 (range, 0.2-26.3 cm3) but was reduced to 2.3 cm3 (range, 0.1-18.2 cm3) by the time of the second procedure.

Dr. Hideyuki Kano

At 3, 4, 5, and 10 years after the second procedure, angiography or magnetic resonance imaging showed rates of AVM obliteration of 35%, 68%, 77%, and 80%, respectively. The median time to complete obliteration was 39 months. Higher rates of AVM eradication were associated with a small residual volume (P = .038) and at least 50% volume reduction (P = .014) after the first GKSR. Hemorrhage occurred in 17 patients (16%) after the repeat procedure, and 6 died.

AVM hemorrhage risk decreased over the years after the second procedure. In the interprocedure period, 7 patients (7%) experienced a hemorrhage. After the second procedure, the rate of new hemorrhages decreased to 4.05% per year for years 0 to 2 and to 1.79% per year for years 2 to 10.

Dr. Kano reported that a larger number of prior hemorrhages (P = .008), a larger AVM target volume (P = .002), an initial AVM volume reduction less than 50% (P = .034), and a higher Pollock-Flickinger score (P = .01), an AVM scoring system that correlates with patient outcome, were associated with a higher risk for hemorrhage after the second GKSR. Five patients (4.7%) developed symptomatic adverse effects from the radiation of the initial procedure as did 10 patients (9.5%) after the second one.

Senior author Dade Lunsford, MD, professor of neurosurgery at the University of Pittsburgh, said the major findings of the study are that patients may not have complete cure of their AVM after their initial procedure and that many can have complete closure of the AVM in the 3 to 5 years after a second GKSR procedure.

Dr. Dade Lunsford

"With a second procedure, since we can get rid of the AVM in about two-thirds of the patients, we can then reduce the risk of future bleeding to less than 1% for the remainder of their life" as a cumulative risk, he said.

A long period of observation, as in this study, is important to know the real residual bleeding risk. "Those [patients] that have smaller-volume AVMs in deep-seated locations that have already responded initially to the first procedure are the best candidates," Dr. Lunsford said. "Most of these patients select radiosurgery because of the deep location of their AVM and the high-risk factors that are associated with [open] surgery."

He said early and late adverse effects of the procedure are related to the location and the volume of the AVM. "Fortunately, in this experience, the risk of a second treatment proved to be relatively low in terms of long-term injury of the brain tissue surrounding the AVM, but there is a risk in the range of several percent of developing a cyst in the target volume of the AVM," he said. "In comparison to the risks of these being treated by open surgery, these risks seem to be significantly lower than what we could achieve by standard surgical techniques."

About 90% of patients who had closure of their AVMs had no new neurologic signs or symptoms, and for those who did, about half were temporary. Fewer than 5% of patients developed permanent new neurologic signs or symptoms after the second procedure.

Mark Linskey, MD, associate professor and chairman of the Department of Neurological Surgery at the University of California, Irvine, congratulated the researchers for their study but noted that it is a retrospective case review series with no control arm, yet he said that it is one of the largest series reported so far. He called the median follow-up of 6.6 years "very respectable" and said the study points up the fact that failures still occur with initial radiosurgery.

The causes of failure were identified in half the cases, giving a lead on how to eliminate them in the future. Dr. Linskey said among the causes were inadequate 3-dimensional volume assessment and possible inadequate radiation doses. "We also learned that repeat radiosurgery works, but it may take a little longer," he said, compared with after an initial procedure.

The work was funded by a research grant to Dr. Kano from Elekta AB of Stockholm, Sweden, the manufacturer of the Gamma Knife system. Dr. Lunsford is a consultant for, has received research support from, and is a stockholder in Elekta AB. Dr. Linskey has disclosed no relevant financial relationships.

American Association of Neurological Surgeons (AANS) 79th Annual Meeting: Oral Presentation. Presented April 11, 2011.


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