PII S0360-3016(99)00513-1 CLINICAL INVESTIGATION Central Nervous System DEVELOPMENT OF A MODEL TO PREDICT PERMANENT SYMPTOMATIC POSTRADIOSURGERY INJURY FOR ARTERIOVENOUS MALFORMATION PATIENTS JOHN C. FLICKINGER, M.D.,* ² DOUGLAS KONDZIOLKA, M.D.,* ² L. DADE LUNSFORD, M.D.,* ²‡ AMIN KASSAM, M.D., ²§ LOI K. PHUONG,M.D.,  ROMAN LISCAK, M.D., ¶ AND BRUCE POLLOCK, M.D.  FOR THE ARTERIOVENOUS MALFORMATION RADIOSURGERY STUDY GROUP Departments of *Radiation Oncology, ² Neurological Surgery, ‡ Radiology, and § Biostatistics, University of Pittsburgh School of Medicine, Pittsburgh, PA;  Department of Neurosurgery, Mayo Clinic, Rochester, MN; and ¶ Department of Neurosurgery, Hospital Na Homolce, Prague, Czech Republic Purpose: To better predict permanent complications from arteriovenous malformation (AVM) radiosurgery. Methods and Materials: Data from 85 AVM patients who developed symptomatic complications following gamma knife radiosurgery and 337 control patients with no complications were evaluated as part of a multi- institutional study. Of the 85 patients with complications, 38 patients were classified as having permanent symptomatic sequelae (necrosis). AVM marginal doses varied from 10 –35 Gy and treatment volumes from 0.26 – 47.9 cc. Median follow-up for patients without complications was 45 months (range: 24 –92). Results: Multivariate analysis of the effects of AVM location and the volume of tissue receiving 12 Gy or more (12-Gy-Volume) allowed construction of a significant postradiosurgery injury expression (SPIE) score. AVM locations in order of increasing risk and SPIE score (from 0 –10) were: frontal, temporal, intraventricular, parietal, cerebellar, corpus callosum, occipital, medulla, thalamus, basal ganglia, and pons/midbrain. The final statistical model predicts risks of permanent symptomatic sequelae from SPIE scores and 12-Gy-Volumes. Prior hemorrhage, marginal dose, and Marginal-12-Gy-Volume (target volume excluded) did not significantly improve the risk-prediction model for permanent sequelae (p > 0.39). Conclusion: The risks of developing permanent symptomatic sequelae from AVM radiosurgery vary dramati- cally with location and, to a lesser extent, volume. These risks can be predicted according to the SPIE location-risk score and the 12-Gy-Volume. © 2000 Elsevier Science Inc. Radiosurgery, Stereotactic surgery, Arteriovenous malformation, Complications, Radiation injury. INTRODUCTION Radiosurgery is a highly effective way of reducing the risk of hemorrhage in properly selected patients with cerebral arteriovenous malformations (AVM) (1–3). Radiosurgery induces an injury response in the AVM nidus leading to eventual complete obliteration in 60 to 90% of cases, de- pending upon AVM size, configuration, as well as the radiosurgery targeting and treatment techniques used (1–3). AVM radiosurgery can sometimes unfortunately induce un- wanted radiation injury in surrounding brain tissue (4 –10). Magnetic resonance (MR) scans show postradiosurgery im- aging changes in the brain surrounding AVM in approxi- mately 30% of patients, depending on the treatment volume and, to a lesser extent, the dose administered (4 –7). Fortu- nately, these effects are asymptomatic in two-thirds of the affected patients, so that symptomatic postradiosurgery se- quelae develop only in approximately 9% of patients (4 –7). Delayed effects of radiosurgery are difficult to study because of the time needed for their development, the ne- cessity to distinguish temporary from permanent injury with additional follow-up, and the variability introduced by dif- ferences in location, treatment volume, and radiation dose distributions. Prior studies focused first on the endpoint of combined symptomatic and asymptomatic postradiosurgery imaging changes without regard to permanence because of limited data and the greater number of events to study (4, 7). The total volume of tissue receiving 12 Gy or more (includ- ing the target), termed the “12-Gy-Volume” was found to accurately reflect the risk of developing postradiosurgery imaging changes (4). The 12-Gy-Volume, which depends Reprint requests to: John C. Flickinger, M.D., Joint Radiation Oncology Center, 200 Lothrop Street, Pittsburgh, PA 15213. E- mail: jflickin+@pitt.edu Acknowledgments—The following other members of the Arterio- venous Malformation Radiosurgery Study Group contributed to this study: D. A. Gorman, P. J. Schomberg (Mayo Clinic), P. Sneed, D. Larson, V. Smith, M. W. McDermott, L. Miyawaki (U. C. San Francisco), J. Yamamoto (Tokyo), J. Chilton (Midwest Gamma Knife Center, Kansas City), R. A. Morantz, B. Young (U. of Kentucky), H. Jokura (Tohoku U., Sendai, Japan). Accepted for publication 15 November 1999. Int. J. Radiation Oncology Biol. Phys., Vol. 46, No. 5, pp. 1143–1148, 2000 Copyright © 2000 Elsevier Science Inc. Printed in the USA. All rights reserved 0360-3016/00/$–see front matter 1143