Dr. Kano is going to talk to us about how to improve obliteration rates during volume stage stereotactic radiosurgery for large AVMs. Thank you, Chairperson. I'd like to talk about volume stage gamma knife for large AVMs. In 1992, we prospectively began to stage anatomic component in order to deliver higher single doses to AVM more than 10 cc in volume. Type A group suggested that increasing the percent volume of an AVM receiving a higher dose may improve obliteration rate. We retrospectively evaluated this hypothesis in our staged radiosurgery series of large AVMs. This MRI shows a volume stage gamma knife planning. Yellow line are margin dose to the half volume, the nidus, and the blue line are the first stage gamma knife plan in the bottom images. In this study, the number of large volume AVMs who underwent volume stage gamma knife was 60. 72% of patients had AVM in the cerebellar hemisphere, 12% in the thalamus, 12% in the basal ganglia, 5% in the cerebellum. 43% of patients had prior hemorrhage before gamma knife, 43% had prior embolization. The median nidus volume was 11.6 cc in the first stage gamma knife and 10.6 cc in the second stage. The median margin dose was 16 gray in both stage gamma knife. Median interval between the first and the second gamma knife was 4.5 months. Median follow-up after the second stage gamma knife was 82 months. This Kaplan-Meier curve shows AVM total obliteration on angiography after stage gamma knife in entire series. The five-year total obliteration rate was only 23%. This Kaplan-Meier curve shows AVM total obliteration after volume stage gamma knife comparing margin dose of 17 gray or more and less than 17 gray. In the group of more than 17 gray margin dose, the five-year total obliteration rate was 43%. More than 70 gray margin dose did improve total obliteration rate but proved insufficient. Do obliteration rate improve if a larger percent of the nidus received a higher dose? Here we have evaluated 18 gray volume, 20 gray volume, and 24 gray volume for each stage. For example, 20 gray volume, this green line, means the volume received more than 20 gray in the nidus. And then we calculated the 20 gray volume coverage rate. Formula is total 20 gray volume divided by total nidus volume. The left scatter plot shows the relationship between total target volume and the margin dose. The right scatter plot shows the relationship between 20 gray volume coverage rate and margin dose. Variation in the prescribed margin dose was also associated with variation in the percent volume that received more than 20 gray. In the univariate analysis, factors associated with the higher rate of total obliteration included higher margin dose, more than 70 gray margin dose, higher 18 gray volume coverage, and higher 20 gray volume coverage. In multivariate analysis, only 20 gray volume coverage was significantly associated with total obliteration. 20 gray volume coverage, more than 63%, was the best predictor of total obliteration. We found the cutoff value was 63%. This Kaplan-Meier curve shows ABM total obliteration after stitched gamma knife, comparing 20 gray volume coverage rate of more than 60% or less than 63%. In the group of 63% of 20 gray volume coverage, the five-year total obliteration rate increased to 61%. Here we excluded patients who underwent prior surgical resection and prior embolization. 30 patients underwent volume-stitched gamma knife as an initial treatment. In the group of more than 60% of 20 gray volume coverage in primary gamma knife series, five-year total obliteration rate was 56%. On the other hand, in the group of less than 63% 20 gray volume coverage, five-year total obliteration was zero. So how can we increase 20 gray volume coverage? Upper image shows original first-stage gamma knife plan for large left occipital AVM. Seven shots of 8-millimeter isocenter was used. 20 gray volume coverage rate was 56%. Less than 60% of 20 gray volume coverage will decrease total obliteration rate. Lower images show simulated first-stage gamma knife plan. 20 shots of 4-millimeter isocenter were used. 20 gray volume coverage rate was 71% increasing. Now more than 63% leads to increase total obliteration rate. Multiple smaller isocenters can significantly increase the 20 gray volume coverage rate. Symptomatic adversarialization effect after first-stage gamma knife occurred in one of 60 patients. After stage gamma knife, for patients, 7% developed symptomatic adversarialization effect to a transient and to a permanent symptom. Volume-stage gamma knife with relatively lower risk of adversarialization effect. In conclusion, the final obliteration rate after stage gamma knife for large-volume AVM can be increased if more than 63% of the volume received more than 20 gray. In addition, prescribing a minimum margin dose of 17 gray to large-volume AVM treated in two-stage, we now add additional internodal isocenters to increase the percentage of the AVM volume that received at least 20 gray. Selectively, dose follow-up is left unchanged, thereby not increasing the risk of adversarialization effect. That's all I have to say. Thank you very much.

obliteration rates

AVMs

gamma knife planning

volume coverage rate

isocenters