Case Study Staged-Volume Radiosurgery of Large AVMs Using Gamma Knife Technology Institution New York University Langone Medical Center Location New York City, NY Patient 18 patients Diagnosis Each patient diagnosed with an arteriovenous malformation (range 15.7-50 ml) Plan Gamma Knife radiosurgery
Authors: Paul P. Huang, M.D. 1 Stephen C. Rush, M.D. 2 Bernadine Donahue, M.D. 2 Ashwatha Narayana, M.D. 2 Tibor Becske, M.D. 3 P. Kim Nelson, M.D. 3 Kerry Han, Ph.D. 2 Jafar J. Jafar, M.D. 1 Departments of 1 Neurosurgery, 2 Radiation Oncology, and 3 Radiology (Interventional Neuroradiology), NYU Langone Medical Center, New York, New York Staged-Volume Radiosurgery of Large AVMs Using Leksell Gamma Knife Technology Introduction Although Gamma Knife surgery has been shown to provide high cure rates and low risk compared to other therapies in the treatment of brain arteriovenous malformations (AVMs), one of the most challenging is the treatment of large, complex AVMs. Increasing the dose to account for the AVM s size risks complications to surrounding tissues, while reducing the treatment dose to acceptable levels increases treatment failures. NYU researchers prospectively treated 18 patients with large AVMs between 1998 and 2011 using a method called staged-volume radiosurgery, which divides the AVM into separate anatomic volumes for treatment in stages. Figure 1. Leksell Gamma Plan treatment planning software showing the treatment plan for the first of two planned treatment volumes. 2
Methods Angiographic and 3D MRI images of the patients AVMs (range 15.7-50 ml) were exported to Leksell Gamma Plan treatment planning software, and each AVM was divided into 10- to 12-mL volumes when possible. The AVM was divided into two volumes in 10 patients, three volumes in five patients, and four volumes in three patients. All volumes received a minimum of 15 Gy to the margin, using the center s Leksell Gamma Knife system. Separate anatomic volumes encompassing the entire nidus were irradiated at three- to nine-month intervals. Over a period of years, sequential follow-up MRIs and angiograms were obtained for each patient to determine the impact of Gamma Knife surgery on the AVM. Patients were classified as cured only if researchers were able to document angiographic closure of their AVM. Figure 2a. AP carotid (A), lateral dual-vessel carotid/vertebral (B), and vertebral artery (C, D) angiograms of a 54-year-old patient with a large left AVM in the thalamus and medial temporal and occipital lobes. E, axial MRI image shows flow voids in the left thalamus, left medial temporal, and left occipital lobes. Total treatment volume was 22.9 ml. AP (F) and lateral (G) carotid angiograms acquired four years posttreatment depict a small residual nidus (arrows) in the left occipital lobe. The patient received repeat Gamma Knife surgery of the residual nidus. AP (H) and lateral (I) carotid angiograms acquired three years post-retreatment show complete closure of the AVM. Results The clinical outcomes of each patient are presented in Table 1. Sixteen patients were followed for a minimum of three years, and 12 had initial follow-up angiography. Five patients showed complete occlusions and seven showed residual disease. Overall, there was an 83.6% reduction in AVM volume at four years, with an initial mean AVM volume of 26.29 ml and a residual mean volume of 4.33 ml. Residual volumes were all under 13 ml. Retreatment was performed in a single session in all seven cases. All patients were treated to the 50% isodose margin. The median dose to the margin in retreated patients was 18 Gy (range, 15-24 Gy). Six of the seven retreated patients received follow-up angiography at a minimum of three years after retreatment. All 6 patients showed complete closure of their AVMs. A follow-up angiogram is pending for the seventh patient. To date, NYU researchers have demonstrated angiographic closure in 11 of the 18 patients for an overall occlusion rate of 61.1%. Kaplan-Meier analysis shows an angiographic occlusion rate of 29% by five years and 89% by 10 years (Figure 3). In terms of hemorrhage risk, five of the 18 patients (27.8%) experienced a hemorrhage after the first treatment cycle, however no hemorrhages were observed beyond the first five years after treatment. Actuarial analysis shows that the cumulative rates of hemorrhage remained stable beyond five years. Within the first five years post-treatment, the hemorrhage rate was 7.8% per patient-years. Beyond five years, the annual rate of hemorrhage was zero over 54 patientyears with a mean follow-up of 6.8 years (range, 1-13 years). 3
No. Initial Size (ml) 1 22.9 2 19.2 3 18.5 4 19.1 5 20.3 6 19.4 7 26 8 36.4 9 16.8 10 15.7 11 22.9 12 27.1 13 22.7 14 46.4 15 32.1 16 32.3 17 50 18 25.4 Table 1. Treatment and Results *Digital Subtraction Angiography Treatment Volumes (ml) 12.5 10.9 10.6 10.5 9.6 10.3 10.3 9.8 10.5 10.9 10.1 11 10.5 10 6.5 9.7 10.2 Residual Volume (ml) 4 Time to Retreatment (months) Obliteration 3.6 63 * 1.6 59 0.5 49 8 57 2.2 43 12.9 69 Hemorrhage, expired 11.1 MRI with absence of flow 6.3 voids, declined DSA 6.2 10.3 11.5 12.1 10.9 11.6 5.3 11.7 11.8 12 11.4 10.8 13.3 10.8 12.8 9.8 11.6 11.4 10.8 12.2 12.9 12.6 13.4 12.1 12.9 5.5 1.5 49 Residual treated, await f/u angio
Figure 3. Kaplan-Meier curve showing the angiographic occlusion rates after staged-volume radiosurgery. Conclusion Staged-volume Gamma Knife radiosurgery for AVMs larger than 15 ml is a practical treatment approach, providing long-term occlusion rates and low risk of radiation-related complications. Hemorrhage risk during the latency period remains the largest source of morbidity and mortality. Leksell Gamma Knife Perfexion offers advantages in staged-volume SRS of AVMs Improvements in Leksell Gamma Knife Perfexion facilitate more efficient planning of staged-volume SRS AVM cases, according to NYU s Dr. Paul P. Huang. Before Perfexion technology was available, when a patient would return in three months to get their second or third treatment, I would have to open up their previous study in a different window and flip back and forth between the studies to try to visually reconstruct the previous margins using anatomic landmarks, he explains. The big advantage of Perfexion and Leksell Gamma Plan 10 treatment planning software is that you can actually overlay a previous stage or stages on top of the new angio or MRI images. The software essentially will match the skull of your current study with the skull from a previous study and line them up perfectly. It makes a big difference and is much easier to plan the treatments. With the advanced Perfexion collimator, the planning of shots also is a much more refined process, he adds. With Perfexion, there are a lot of advantages as to how the shots are set up, Dr. Huang says. You can now do hybrid shots, where previously we had been limited to perhaps three different choices. With Perfexion, you draw your volume and the computer can then generate the shots for you within the volume you re defining. For the more complicated volumes, you can easily reduce your planning time by half. In addition, with Perfexion, clinicians need no longer change coordinates in between every shot a process that could be very time-consuming when dealing with a 20-shot volume, he adds. That could easily double your treatment time, not just your planning time, Dr. Huang notes. With Perfexion, all of the coordinates for each shot are changed automatically which is a big timesaver. Leksell Gamma Knife Perfexion is a teletherapy device intended for stereotactic irradiation of head structures ranging from very small target sizes of a few millimeters to several centimeters e.g. metastatic tumors, arteriovenous malformations, trigeminal neuralgia, meningiomas and vestibular schwannomas. 5
Reference Huang, Paul P. MD; Rush, Stephen C. MD; Donahue, Bernadine MD; Narayana, Ashwatha MD; Becske, Tibor MD; Nelson, P. Kim MD; Han, Kerry PhD; Jafar, Jafar J. MD. Long-term Outcomes After Staged-Volume Stereotactic Radiosurgery for Large Arteriovenous Malformations. Neurosurgery, September 2012, Volume 71:Issue 3, p 632-644. www.elekta.com Corporate Head Office: Elekta AB (publ) Box 7593, SE-103 93 Stockholm, Sweden Tel +46 8 587 254 00 Fax +46 8 587 255 00 info@elekta.com Regional Sales, Marketing and Service: North America Tel +1 770 300 9725 Fax +1 770 448 6338 info.america@elekta.com Europe, Middle East, Africa, Eastern Europe, Latin America Tel +46 8 587 254 00 Fax +46 8 587 255 00 info.europe@elekta.com Asia Pacific Tel +852 2891 2208 Fax +852 2575 7133 info.asia@elekta.com Human Care Makes the Future Possible Document no. 1500427.00 AUG2012 2012 Elekta Ltd. All mentioned trademarks and registered trademarks are the property of the Elekta Group. All rights reserved. No part of this document may be reproduced in any form without written permission from the copyright holder.