- Email: [email protected]
Is Stereotactic Radiosurgery the Best Treatment Option for Patients with a Radiosurgery-based Arteriovenous Malformation Score ≤1?
Peer-Review Reports
Is Stereotactic Radiosurgery the Best Treatment Option for Patients with a Radiosurgery-based Arteriovenous Malformation Score 1? Anthony M. Burrow1, Michael J. Link1,3, Bruce E. Pollock1,2
Key words Arteriovenous malformation - Grading scale - Stereotactic radiosurgery -
Abbreviations and Acronyms AVM: Arteriovenous malformation BAVM: Brain arteriovenous malformation CI: Confidence interval MRI: Magnetic resonance imaging MRS: Modified Rankin score RBAS: Radiosurgery-based AVM score SRS: Stereotactic radiosurgery From the Departments of 1Neurological Surgery, 2 Radiation Oncology, and 3Otorhinolaryngology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA To whom correspondence should be addressed: Bruce E. Pollock, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2014). http://dx.doi.org/10.1016/j.wneu.2014.07.009 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2014 Elsevier Inc. All rights reserved.
- OBJECTIVE:
The best management of patients with brain arteriovenous malformations (BAVM) is controversial. The radiosurgery-based arteriovenous malformation (AVM) score (RBAS) was developed to predict outcomes for patients with BAVM having stereotactic radiosurgery (SRS).
- METHODS:
The RBAS is calculated for patients with BAVM having SRS at our center as part of our prospectively maintained SRS database (RBAS [ [0.1] [AVM volume; cm3] D [0.02] [patient age; years] D [0.5] [AVM location; 0 [ cerebral/cerebellar hemispheres/corpus callosum, 1 [ basal ganglia/thalamus/ brainstem]). Review of the SRS database from 1990 to 2009 identified 80 patients with a RBAS £1 and at least 1 year of follow-up. The primary end point of the study was a decline in modified Rankin Score. The mean follow-up after SRS was 68 months (range, 12L133).
- RESULTS:
The mean patient age was 25.2 years (range, 7L44). Seventy-six patients (95%) had superficially located BAVMs; the mean BAVM volume was 2.3 cm3 (range, 0.1L8.0). The mean RBAS was 0.76 (range, 0.21L1.00). The patients’ MRS before SRS was 0 (n [ 52, 65%), 1 (n [ 24, 30%), 2 (n [ 3, 4%), and 3 (n [ 1, 1%). BAVM obliteration was confirmed in 92% of patients with follow-up beyond 3 years (70/76; 95% confidence interval 84%L97%). No patient had a hemorrhage or a radiation-related complication after SRS. The observed rate of modified Rankin Score decrease after SRS was 0% (0/80; 95% confidence interval 0%L6%).
- CONCLUSIONS:
INTRODUCTION The management of patients with brain arteriovenous malformations (BAVMs) is complex and depends on a number of factors, including presentation, patient age, and size and location of the BAVM. Treatment options for patients include observation (12), surgical resection (3, 4, 6, 9, 10, 23, 24), embolization (8, 11, 21), stereotactic radiosurgery (SRS) (1, 2, 5, 7, 15-17, 19, 20, 26), or a combination of these different techniques. Conservative management (observation) recently has received a great deal of attention because the prospective trial A Randomized trial of Unruptured Brain Arteriovenous malformations was stopped secondary to the high risk of intervention compared with the risk of observation (12). The SpetzlerMartin grading scale is the most widely used system to stratify the risk of BAVM surgical resection based on the BAVM size, BAVM location, and the presence or absence of deep venous drainage (23). In
SRS provided a high rate of obliteration at very low risk for patients with BVAM with a RBAS £1. Patient outcomes after SRS are likely equivalent to resection for younger patients with small-volume BAVM who do not require a craniotomy for clot removal.
2002, the radiosurgery-based AVM score (RBAS) was introduced to predict the chance of BAVM obliteration without new neurologic deficits after single-fraction SRS (16). The RBAS was simplified in 2008 with regard to BAVM location (17) and has been shown to predict outcomes accurately independent of the radiation delivery technique (1, 2, 5, 14, 19, 20, 26). In the present study, we present the outcomes of patients with BAVM having single-fraction SRS at our center between 1990 and 2009 whose RBAS 1.0. METHODS Patients All aspects of this retrospective study were approved by the Mayo Clinic Institutional
WORLD NEUROSURGERY - [-]: ---, MONTH 2014
Review Board, Rochester, Minnesota, USA. A prospective database of all patients having single-fraction SRS at the Mayo Clinic, Rochester, Minnesota, USA from 1990 to 2009 was reviewed. Within the database are patient and BAVM characteristics including pre-SRS functional status as measured by the modified Rankin Score (MRS), the radiosurgical dosimetry, and post-SRS clinical and radiologic follow-up. The RBAS is calculated by the following equation [(0.1) (AVM volume; cm3) þ (0.02) (patient age; years) þ (0.5) (AVM location; 0 ¼ cerebral/cerebellar hemispheres/corpus callosum, 1 ¼ basal ganglia/thalamus/ brainstem)] (17). Eighty-five patients (18% of the total BAVM series) were identified with BAVM and a RBAS 1.0. Five patients had less than 12 months of follow-up and
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PEER-REVIEW REPORTS IS SRS BEST FOR PATIENTS WITH AN AVM SCORE 1?
ANTHONY M. BURROW ET AL.
were excluded from further analysis. The characteristics of the remaining 80 patients are outlined in Table 1. The mean RBAS of the patients was 0.76 (range, 0.171.0).
Stereotactic Radiosurgery All the radiosurgical procedures were performed in a single-fraction using various versions of the Leksell Gamma Knife (Elekta Inc, Atlanta, Georgia, USA). Dose planning was performed using a combination of stereotactic bi-plane angiography and stereotactic magnetic resonance imaging (MRI). The mean treatment volume was 2.3 cm3 (range, 0.18.0). The mean BAVM margin dose was 21.0 Gy (range,
Table 1. Patient Characteristics Parameter Sex
Value 31 male/49 female
Mean age, years (range)
25.2 (544)
Presentation, n (%) Hemorrhage Seizure Other
33 (41) 9 (11) 38 (48)
Location, n (%) Cerebral hemisphere
69 (86)
Corpus callosum
4 (5)
Cerebellar hemisphere
2 (3)
Thalamus
3 (4)
Basal ganglia
1 (1)
Midbrain
1 (1)
Eloquent brain location, n (%)* Yes
56 (70)
No
24 (30)
Spetzler-Martin grade, n (%) III
48 (60)
IIIa
3 (4)
IIIb
29 (36)
Previous treatment Resection
10 (13)
Clot evacuation
4 (5)
Embolization
2 (2)
*According to the criteria of the Spetzler-Martin grading system (23).
2
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1625). The mean maximum BAVM dose was 40.3 Gy (range, 2250). Follow-up after SRS (mean, 68 months) consisted of clinical examination and MRI at 1, 2, and 3 years after radiosurgery. Follow-up angiography was recommended at 35 years after SRS to determine the obliteration status of the AVM. Patients with residual BAVM on follow-up angiography were re-evaluated for repeat radiosurgery or surgical resection. Ten patients (13%) underwent repeat SRS. No patient underwent surgical resection of their BAVM after SRS. Statistical Analysis The primary outcome measure was a decrease in MRS after SRS. Confidence intervals (CIs) were calculated using the modified Wald method. RESULTS BAVM Obliteration The BAVM obliteration status was determined by catheter angiography in 54 patients (70%) and by MRI in 26 patients (30%). BAVM obliteration was noted in 70 of 76 patients (92%; 95% CI 84%97%) with follow-up imaging performed three or more years after SRS (Figure 1). Functional Outcomes At the time of SRS, the patients’ MRS were 0 (n ¼ 52, 65%), 1 (n ¼ 24, 30%), 2 (n ¼ 3, 4%), and 3 (n ¼ 1, 1%). After SRS, no patient suffered a hemorrhage or radiationrelated complication. The observed rate of MRS decline after SRS was 0% (0/80; 95% CI 0%6%). DISCUSSION A rationale approach to the management of patients with BAVM should be based on an objective comparison of the risks for conservative therapy against the risks for the treatment options used to eradicate BAVM. Patients who present after a hemorrhage, especially if the BAVM is not large and is located superficially, should undergo surgical resection to eliminate the future risk of bleeding (3, 4, 9, 14, 23, 24); however, patients are diagnosed more frequently with unruptured BAVM, and the morbidity associated with the removal of critically located lesions can be significant. Consequently, endovascular therapy and SRS
frequently are considered as alternatives to surgical excision in these situations. Over the years, a number of classification schemes have been developed to help guide the decision-making process for patients with BAVM. Far and away, the SpetzlerMartin grading system is the most widely used method, having been validated by numerous cerebrovascular centers as reliable and practical in predicting patient outcomes after surgical resection of BAVM (23). Although some authors have suggested that further subdivision of Grade III BAVM is necessary (4, 10), most published reports on BAVM resection support a simplification of the original SpetzlerMartin system that reflects the general treatment approach for these lesions. Spetzler and Ponce described a three-tiered classification which combines Grades I and II (Class A) and Grades IV and V (Class C) (24). Class B comprises Spetzler-Martin Grade III BAVM. Combining the results of seven large surgical series, the respective rate of negative outcomes for Classes A (n ¼ 735), B (n ¼ 455), and C (n ¼ 286) were 8%, 18%, and 32%, respectively. On the basis of these data, the authors proposed a management algorithm in which the primary treatment of Class A BAVM is resection, Class B BAVM is multimodality treatment, and Class C BAVM is observation (with exceptions for patients with recurrent hemorrhages, progressive neurological deficits, or BAVM-related aneurysms). Despite the strong evidence that resection is the preferred treatment for patients with Class A BAVM, the selection bias present in these surgical series is a confounding variable of any post-hoc analysis (25). Kano et al. (7) recently reported the outcomes of 217 patients with SpetzlerMartin Grade I or II BAVM having singlefraction SRS between 1987 and 2006. The patients’ RBAS ranged from <1.0 (n ¼ 88, 41%) to >1.5 (n ¼ 40, 18%); the median follow-up period after SRS was 64 months (range, 6267). BAVM obliteration at 5 years after SRS was noted in 90% of patients when both MRI and angiography criteria was used and in 86% of patients when based on angiography alone. Thirteen patients (6%) had a hemorrhage after SRS. The actuarial 5-year risk of post-SRS bleeding was 5%. Importantly, 6 patients (3%) died secondary to bleeding after SRS. No patient suffered a permanent radiation-related deficit. In the present series,
WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2014.07.009
PEER-REVIEW REPORTS IS SRS BEST FOR PATIENTS WITH AN AVM SCORE 1?
ANTHONY M. BURROW ET AL.
Figure 1. A 16-year old male patient with headaches but no evidence of hemorrhage. (A) T1-weighted axial magnetic resonance imaging (B) and right internal carotid artery angiogram (right) show a 2.5-cm Spetzler-Martin Grade IIIb AVM located in the right gyrus rectus. The AVM volume was
49 patients (61%) had Spetzler-Martin Grade I-II (Class A) BAVM, whereas 31 patients (39%) had Grade III (Class B) BAVM. The majority of Class B BAVM (28/ 31, 90%) were <3 cm in largest diameter but were located in critical regions and had deep venous drainage (Grade IIIb) (4). These examples highlight that although there is clearly an overlap in what are considered ideal patients for surgical resection using the Spetzler-Martin system (Class A) or SRS using the RBAS (1.00), specific considerations of the different techniques make neither classification scheme universally applicable. The RBAS was created as an instrument to predict outcomes for BAVM patients based on factors relevant to SRS. During the past 12 years, the RBAS has been validated by not only centers performing Gamma Knife SRS (5, 15, 19) but also has proven to accurately predict outcomes after linear acceleratorbased and CyberKnife procedures (1, 2, 20, 26). The RBAS has been cited more than 200 times and has been described as “the radiosurgical equivalent of the Spetzler-Martin grading system” (22). In our experience, the RBAS has permitted the identification of a subgroup of patients with BAVM, defined as having a RBAS 1.0, who have a high rate of obliteration with a low risk of morbidity secondary to either post-SRS bleeding or radiation-related complications. Other centers have reported that between 87% and 92% of patients with BAVM with a
5.4 cm3; the RBAS was 0.99. (C) Complete obliteration was confirmed 45 months after SRS by cerebral angiography. AVM, arteriovenous malformation; RBAS, radiosurgery-based AVM score; SRS, stereotactic radiosurgery.
RBAS 1.0 achieve obliteration without new neurologic deficits after SRS (1, 20). Recently we published the outcomes after SRS for patients who would have been eligible for inclusion in the A Randomized trial of Unruptured Brain Arteriovenous malformations trial (19). Using the same primary outcome measure to determine the risk of death or clinical impairment (defined as a MRS 2), we found that the 10-year risk of MRS 2 for patients with a RBAS 1.50 was 2% compared with 18% for patients with a RBAS >1.50. Earlier work also showed that the RBAS correlated with a decrease in MRS after SRS for patients with both ruptured and unruptured BAVM (15). Our study has several limitations that need to be considered when interpreting our results. First, the study is a single-center, retrospective analysis. Second, the number of patients (n ¼ 80) in our series is relatively small, which limited the power of any statistical analysis. Third, BAVM obliteration after SRS was determined by a combination of both angiography and MRI. Thus, the actual number of patients with obliteration may have been overestimated in our series. However, numerous studies have shown a high correlation between MRI and angiographic obliteration (82% and 91%) (13, 18), so the observed obliteration rate would not change significantly if we relied solely on post-SRS angiography to determine obliteration. Fourth, the mean follow-up period was less than 6 years, so
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there is a chance of late radiation-related complications being missed in our review. Finally, this study has no control group so the quality of the data on the relative effectiveness of SRS to observation, surgical resection, or endovascular therapy for this patient group is poor. However, it is unlikely that a randomized trial comparing SRS with the other treatment options would be successfully organized and completed, so treatment recommendations will continue to rely on lower classes of evidence for the foreseeable future. CONCLUSIONS Single-fraction SRS provided a high rate of obliteration at negligible risk for BAVM patients with a RBAS 1. Patient outcomes after SRS are likely equivalent to resection for younger patients with small, critically located AVMs who do not require a craniotomy for clot removal. REFERENCES 1. Andrade-Souza YM, Zadeh G, Ramani M, Scora D, Tsao MN, Schwartz ML: Testing the radiosurgerybased arteriovenous malformation score and the modified Spetzler-Martin grading system to predict radiosurgical outcome. J Neurosurg 103: 642-648, 2005. 2. Colombo F, Cavedon C, Casentini L, Francescon P, Causin F, Pinna V: Early results of CyberKnife radiosurgery for arteriovenous malformations. J Neurosurg 111:807-819, 2009. 3. Davidson AS, Morgan MK: How safe is arteriovenous malformation surgery? A prospective,
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PEER-REVIEW REPORTS ANTHONY M. BURROW ET AL.
observational study of surgery as first-line treatment for brain arteriovenous malformations. Neurosurgery 66:498-504, 2010. 4. de Oliveria E, Tedeschi H, Raso J: Comprehensive management of arteriovenous malformations. Neurol Res 20:673-683, 1998. 5. Franzin A, Snider S, Boari N, Scomazzoni F, Picozzi P, Spatola G, Gagliardi F, Mortini P: Evaluation of prognostic factors as predictor of AVMS obliteration after Gamma Knife radiosurgery. Acta Neurochir 155:619-626, 2013. 6. Hamilton MG, Spetzler RF: The prospective application of a grading system for arteriovenous malformations. Neurosurgery 34:2-7, 1994. 7. Kano H, Lunsford LD, Flickinger JC, Yang HC, Flannery TJ, Awan NR, Niranjan A, Novotny J, Kondziolka D: Stereotactic radiosurgery for arteriovenous malformations, Part 1: management of Spetzler-Martin Grade I and II arteriovenous malformations. J Neurosurg 116:11-20, 2012. 8. Katsaridis V, Papagiannaki C, Aimar E: Curative embolization of cerebral arteriovenous malformations (AVMs) with Onyx in 101 patients. Neuroradiology 50:589-597, 2008. 9. Lawton MT, Du R, Tran MN, Achrol AS, McCulloch CE, Johnston SC, Quinnine NJ, Young WL: Effect of presenting hemorrhage on outcome after microsurgical resection of brain arteriovenous malformations. Neurosurgery 56: 485-493, 2005. 10. Lawton MT, Kim H, McCulloch CE, Mikhak B, Young WL: A supplemental grading scale for selecting patients with brain arteriovenous malformations for surgery. Neurosurgery 66:702-713, 2010. 11. Loh Y, Duckwiler GR: A prospective, multicenter, randomized trial of the Onyx liquid embolic system and N-butyl cyanoacrylate embolization of cerebral arteriovenous malformations. Clinical article. J Neurosurg 113:733-741, 2010. 12. Mohr JP, Parides MK, Stapf C, Moquete E, Moy CS, Overby JR, Salman RA, Vicaut E, Young WL, Houdat E, Cordonnier C, Stefani MA, Hartmann A,
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von Kummer R, Biondi A, Berkefeld J, Klijn CJM, Harkness K, Libman R, Barreau X, Moskowitz AJ; for the international ARUBA investigators: Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial. Lancet 2013. 13. O’Connor TE, Friedman WA: Magnetic resonance imaging assessment of cerebral arteriovenous malformation obliteration after stereotactic radiosurgery. Neurosurgery 73:761-766, 2013. 14. Ogilivy CS, Stieg PE, Awad I, Brown RD Jr, Kondziolka D, Rosenwasser R, Young WL, Hademenos G: AHA scientific statement: recommendations for the management of intracranial arteriovenous malformations: a statement for health-care professionals from a special writing group of the Stroke Council, American Stroke Association. Stroke 32:1458-1471, 2001. 15. Pollock BE, Brown RD Jr: Use of the Modified Rankin Scale to assess outcome after arteriovenous malformation radiosurgery. Neurology 67: 1630-1634, 2006. 16. Pollock BE, Flickinger JC: A proposed radiosurgery-based grading system for arteriovenous malformations. J Neurosurg 96:79-85, 2002. 17. Pollock BE, Flickinger JC: Modification of the radiosurgery-based arteriovenous malformation grading system. Neurosurgery 63:239-243, 2008. 18. Pollock BE, Kondziolka D, Flickinger JC, Patel AK, Bissonette DJ, Lunsford LD: Magnetic resonance imaging: an accurate method to evaluate arteriovenous malformations after stereotactic radiosurgery. J Neurosurg 85:1044-1049, 1996. 19. Pollock BE, Link MJ, Brown RD Jr: The risk of stroke or clinical impairment after stereotactic radiosurgery for ARUBA-eligible patients. Stroke 44:437e441. 20. Raffa SJ, Chi YY, Bova FJ, Friedman WA: Validation of the radiosurgery-based arteriovenous malformation score in a large linear accelerator radiosurgery experience. J Neurosurg 111:832-839, 2009.
21. Saatci I, Geyik S, Yav K, Cekirge HS: Endovascular treatment of brain arteriovenous malformations with prolonged intranidal Onyx injection technique: long-term results in 350 consecutive patients with completed endovascular treatment course. J Neurosurg 383:614-621, 2011. 22. Sheehan JP: Comment on Pollock BE, Flickinger JC. Modification of the radiosurgery-based arteriovenous malformation grading system. Neurosurgery 63:243, 2008. 23. Spetzler RF, Martin NA: A proposed grading system for arteriovenous malformations. J Neurosurg 65:476-483, 1986. 24. Spetzler RF, Ponce FA: A 3-tier classification of cerebral arteriovenous malformations. J Neurosurg 114:842-849, 2011. 25. van Beijnum J, van der Worp HB, Buis DR, AlShahi Salman R, Kappelle LJ, Rinkel GJ, van der Sprenkel JWB, Vandertop WP, Algra A, Klijn CJM: Treatment of brain arteriovenous malformations: a systematic review and meta-analysis. JAMA 306: 2011-2019, 2011. 26. Wong GK, Kam MK, Chiu SK, Lam JM, Leung CH, Ng DW, Ngar YK, Poon WS: Validation of the modified radiosurgery-based arteriovenous malformation score in a linear accelerator radiosurgery experience in Hong Kong. J Clin Neurosci 19:1252-1254, 2012.
Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Received 2 January 2014; accepted 8 July 2014 Citation: World Neurosurg. (2014). http://dx.doi.org/10.1016/j.wneu.2014.07.009 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2014 Elsevier Inc. All rights reserved.
WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2014.07.009
Is Stereotactic Radiosurgery the Best Treatment Option for Patients with a Radiosurgery-based Arteriovenous Malformation Score 1? Anthony M. Burrow1, Michael J. Link1,3, Bruce E. Pollock1,2
Key words Arteriovenous malformation - Grading scale - Stereotactic radiosurgery -
Abbreviations and Acronyms AVM: Arteriovenous malformation BAVM: Brain arteriovenous malformation CI: Confidence interval MRI: Magnetic resonance imaging MRS: Modified Rankin score RBAS: Radiosurgery-based AVM score SRS: Stereotactic radiosurgery From the Departments of 1Neurological Surgery, 2 Radiation Oncology, and 3Otorhinolaryngology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA To whom correspondence should be addressed: Bruce E. Pollock, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2014). http://dx.doi.org/10.1016/j.wneu.2014.07.009 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2014 Elsevier Inc. All rights reserved.
- OBJECTIVE:
The best management of patients with brain arteriovenous malformations (BAVM) is controversial. The radiosurgery-based arteriovenous malformation (AVM) score (RBAS) was developed to predict outcomes for patients with BAVM having stereotactic radiosurgery (SRS).
- METHODS:
The RBAS is calculated for patients with BAVM having SRS at our center as part of our prospectively maintained SRS database (RBAS [ [0.1] [AVM volume; cm3] D [0.02] [patient age; years] D [0.5] [AVM location; 0 [ cerebral/cerebellar hemispheres/corpus callosum, 1 [ basal ganglia/thalamus/ brainstem]). Review of the SRS database from 1990 to 2009 identified 80 patients with a RBAS £1 and at least 1 year of follow-up. The primary end point of the study was a decline in modified Rankin Score. The mean follow-up after SRS was 68 months (range, 12L133).
- RESULTS:
The mean patient age was 25.2 years (range, 7L44). Seventy-six patients (95%) had superficially located BAVMs; the mean BAVM volume was 2.3 cm3 (range, 0.1L8.0). The mean RBAS was 0.76 (range, 0.21L1.00). The patients’ MRS before SRS was 0 (n [ 52, 65%), 1 (n [ 24, 30%), 2 (n [ 3, 4%), and 3 (n [ 1, 1%). BAVM obliteration was confirmed in 92% of patients with follow-up beyond 3 years (70/76; 95% confidence interval 84%L97%). No patient had a hemorrhage or a radiation-related complication after SRS. The observed rate of modified Rankin Score decrease after SRS was 0% (0/80; 95% confidence interval 0%L6%).
- CONCLUSIONS:
INTRODUCTION The management of patients with brain arteriovenous malformations (BAVMs) is complex and depends on a number of factors, including presentation, patient age, and size and location of the BAVM. Treatment options for patients include observation (12), surgical resection (3, 4, 6, 9, 10, 23, 24), embolization (8, 11, 21), stereotactic radiosurgery (SRS) (1, 2, 5, 7, 15-17, 19, 20, 26), or a combination of these different techniques. Conservative management (observation) recently has received a great deal of attention because the prospective trial A Randomized trial of Unruptured Brain Arteriovenous malformations was stopped secondary to the high risk of intervention compared with the risk of observation (12). The SpetzlerMartin grading scale is the most widely used system to stratify the risk of BAVM surgical resection based on the BAVM size, BAVM location, and the presence or absence of deep venous drainage (23). In
SRS provided a high rate of obliteration at very low risk for patients with BVAM with a RBAS £1. Patient outcomes after SRS are likely equivalent to resection for younger patients with small-volume BAVM who do not require a craniotomy for clot removal.
2002, the radiosurgery-based AVM score (RBAS) was introduced to predict the chance of BAVM obliteration without new neurologic deficits after single-fraction SRS (16). The RBAS was simplified in 2008 with regard to BAVM location (17) and has been shown to predict outcomes accurately independent of the radiation delivery technique (1, 2, 5, 14, 19, 20, 26). In the present study, we present the outcomes of patients with BAVM having single-fraction SRS at our center between 1990 and 2009 whose RBAS 1.0. METHODS Patients All aspects of this retrospective study were approved by the Mayo Clinic Institutional
WORLD NEUROSURGERY - [-]: ---, MONTH 2014
Review Board, Rochester, Minnesota, USA. A prospective database of all patients having single-fraction SRS at the Mayo Clinic, Rochester, Minnesota, USA from 1990 to 2009 was reviewed. Within the database are patient and BAVM characteristics including pre-SRS functional status as measured by the modified Rankin Score (MRS), the radiosurgical dosimetry, and post-SRS clinical and radiologic follow-up. The RBAS is calculated by the following equation [(0.1) (AVM volume; cm3) þ (0.02) (patient age; years) þ (0.5) (AVM location; 0 ¼ cerebral/cerebellar hemispheres/corpus callosum, 1 ¼ basal ganglia/thalamus/ brainstem)] (17). Eighty-five patients (18% of the total BAVM series) were identified with BAVM and a RBAS 1.0. Five patients had less than 12 months of follow-up and
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PEER-REVIEW REPORTS IS SRS BEST FOR PATIENTS WITH AN AVM SCORE 1?
ANTHONY M. BURROW ET AL.
were excluded from further analysis. The characteristics of the remaining 80 patients are outlined in Table 1. The mean RBAS of the patients was 0.76 (range, 0.171.0).
Stereotactic Radiosurgery All the radiosurgical procedures were performed in a single-fraction using various versions of the Leksell Gamma Knife (Elekta Inc, Atlanta, Georgia, USA). Dose planning was performed using a combination of stereotactic bi-plane angiography and stereotactic magnetic resonance imaging (MRI). The mean treatment volume was 2.3 cm3 (range, 0.18.0). The mean BAVM margin dose was 21.0 Gy (range,
Table 1. Patient Characteristics Parameter Sex
Value 31 male/49 female
Mean age, years (range)
25.2 (544)
Presentation, n (%) Hemorrhage Seizure Other
33 (41) 9 (11) 38 (48)
Location, n (%) Cerebral hemisphere
69 (86)
Corpus callosum
4 (5)
Cerebellar hemisphere
2 (3)
Thalamus
3 (4)
Basal ganglia
1 (1)
Midbrain
1 (1)
Eloquent brain location, n (%)* Yes
56 (70)
No
24 (30)
Spetzler-Martin grade, n (%) III
48 (60)
IIIa
3 (4)
IIIb
29 (36)
Previous treatment Resection
10 (13)
Clot evacuation
4 (5)
Embolization
2 (2)
*According to the criteria of the Spetzler-Martin grading system (23).
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1625). The mean maximum BAVM dose was 40.3 Gy (range, 2250). Follow-up after SRS (mean, 68 months) consisted of clinical examination and MRI at 1, 2, and 3 years after radiosurgery. Follow-up angiography was recommended at 35 years after SRS to determine the obliteration status of the AVM. Patients with residual BAVM on follow-up angiography were re-evaluated for repeat radiosurgery or surgical resection. Ten patients (13%) underwent repeat SRS. No patient underwent surgical resection of their BAVM after SRS. Statistical Analysis The primary outcome measure was a decrease in MRS after SRS. Confidence intervals (CIs) were calculated using the modified Wald method. RESULTS BAVM Obliteration The BAVM obliteration status was determined by catheter angiography in 54 patients (70%) and by MRI in 26 patients (30%). BAVM obliteration was noted in 70 of 76 patients (92%; 95% CI 84%97%) with follow-up imaging performed three or more years after SRS (Figure 1). Functional Outcomes At the time of SRS, the patients’ MRS were 0 (n ¼ 52, 65%), 1 (n ¼ 24, 30%), 2 (n ¼ 3, 4%), and 3 (n ¼ 1, 1%). After SRS, no patient suffered a hemorrhage or radiationrelated complication. The observed rate of MRS decline after SRS was 0% (0/80; 95% CI 0%6%). DISCUSSION A rationale approach to the management of patients with BAVM should be based on an objective comparison of the risks for conservative therapy against the risks for the treatment options used to eradicate BAVM. Patients who present after a hemorrhage, especially if the BAVM is not large and is located superficially, should undergo surgical resection to eliminate the future risk of bleeding (3, 4, 9, 14, 23, 24); however, patients are diagnosed more frequently with unruptured BAVM, and the morbidity associated with the removal of critically located lesions can be significant. Consequently, endovascular therapy and SRS
frequently are considered as alternatives to surgical excision in these situations. Over the years, a number of classification schemes have been developed to help guide the decision-making process for patients with BAVM. Far and away, the SpetzlerMartin grading system is the most widely used method, having been validated by numerous cerebrovascular centers as reliable and practical in predicting patient outcomes after surgical resection of BAVM (23). Although some authors have suggested that further subdivision of Grade III BAVM is necessary (4, 10), most published reports on BAVM resection support a simplification of the original SpetzlerMartin system that reflects the general treatment approach for these lesions. Spetzler and Ponce described a three-tiered classification which combines Grades I and II (Class A) and Grades IV and V (Class C) (24). Class B comprises Spetzler-Martin Grade III BAVM. Combining the results of seven large surgical series, the respective rate of negative outcomes for Classes A (n ¼ 735), B (n ¼ 455), and C (n ¼ 286) were 8%, 18%, and 32%, respectively. On the basis of these data, the authors proposed a management algorithm in which the primary treatment of Class A BAVM is resection, Class B BAVM is multimodality treatment, and Class C BAVM is observation (with exceptions for patients with recurrent hemorrhages, progressive neurological deficits, or BAVM-related aneurysms). Despite the strong evidence that resection is the preferred treatment for patients with Class A BAVM, the selection bias present in these surgical series is a confounding variable of any post-hoc analysis (25). Kano et al. (7) recently reported the outcomes of 217 patients with SpetzlerMartin Grade I or II BAVM having singlefraction SRS between 1987 and 2006. The patients’ RBAS ranged from <1.0 (n ¼ 88, 41%) to >1.5 (n ¼ 40, 18%); the median follow-up period after SRS was 64 months (range, 6267). BAVM obliteration at 5 years after SRS was noted in 90% of patients when both MRI and angiography criteria was used and in 86% of patients when based on angiography alone. Thirteen patients (6%) had a hemorrhage after SRS. The actuarial 5-year risk of post-SRS bleeding was 5%. Importantly, 6 patients (3%) died secondary to bleeding after SRS. No patient suffered a permanent radiation-related deficit. In the present series,
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Figure 1. A 16-year old male patient with headaches but no evidence of hemorrhage. (A) T1-weighted axial magnetic resonance imaging (B) and right internal carotid artery angiogram (right) show a 2.5-cm Spetzler-Martin Grade IIIb AVM located in the right gyrus rectus. The AVM volume was
49 patients (61%) had Spetzler-Martin Grade I-II (Class A) BAVM, whereas 31 patients (39%) had Grade III (Class B) BAVM. The majority of Class B BAVM (28/ 31, 90%) were <3 cm in largest diameter but were located in critical regions and had deep venous drainage (Grade IIIb) (4). These examples highlight that although there is clearly an overlap in what are considered ideal patients for surgical resection using the Spetzler-Martin system (Class A) or SRS using the RBAS (1.00), specific considerations of the different techniques make neither classification scheme universally applicable. The RBAS was created as an instrument to predict outcomes for BAVM patients based on factors relevant to SRS. During the past 12 years, the RBAS has been validated by not only centers performing Gamma Knife SRS (5, 15, 19) but also has proven to accurately predict outcomes after linear acceleratorbased and CyberKnife procedures (1, 2, 20, 26). The RBAS has been cited more than 200 times and has been described as “the radiosurgical equivalent of the Spetzler-Martin grading system” (22). In our experience, the RBAS has permitted the identification of a subgroup of patients with BAVM, defined as having a RBAS 1.0, who have a high rate of obliteration with a low risk of morbidity secondary to either post-SRS bleeding or radiation-related complications. Other centers have reported that between 87% and 92% of patients with BAVM with a
5.4 cm3; the RBAS was 0.99. (C) Complete obliteration was confirmed 45 months after SRS by cerebral angiography. AVM, arteriovenous malformation; RBAS, radiosurgery-based AVM score; SRS, stereotactic radiosurgery.
RBAS 1.0 achieve obliteration without new neurologic deficits after SRS (1, 20). Recently we published the outcomes after SRS for patients who would have been eligible for inclusion in the A Randomized trial of Unruptured Brain Arteriovenous malformations trial (19). Using the same primary outcome measure to determine the risk of death or clinical impairment (defined as a MRS 2), we found that the 10-year risk of MRS 2 for patients with a RBAS 1.50 was 2% compared with 18% for patients with a RBAS >1.50. Earlier work also showed that the RBAS correlated with a decrease in MRS after SRS for patients with both ruptured and unruptured BAVM (15). Our study has several limitations that need to be considered when interpreting our results. First, the study is a single-center, retrospective analysis. Second, the number of patients (n ¼ 80) in our series is relatively small, which limited the power of any statistical analysis. Third, BAVM obliteration after SRS was determined by a combination of both angiography and MRI. Thus, the actual number of patients with obliteration may have been overestimated in our series. However, numerous studies have shown a high correlation between MRI and angiographic obliteration (82% and 91%) (13, 18), so the observed obliteration rate would not change significantly if we relied solely on post-SRS angiography to determine obliteration. Fourth, the mean follow-up period was less than 6 years, so
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there is a chance of late radiation-related complications being missed in our review. Finally, this study has no control group so the quality of the data on the relative effectiveness of SRS to observation, surgical resection, or endovascular therapy for this patient group is poor. However, it is unlikely that a randomized trial comparing SRS with the other treatment options would be successfully organized and completed, so treatment recommendations will continue to rely on lower classes of evidence for the foreseeable future. CONCLUSIONS Single-fraction SRS provided a high rate of obliteration at negligible risk for BAVM patients with a RBAS 1. Patient outcomes after SRS are likely equivalent to resection for younger patients with small, critically located AVMs who do not require a craniotomy for clot removal. REFERENCES 1. Andrade-Souza YM, Zadeh G, Ramani M, Scora D, Tsao MN, Schwartz ML: Testing the radiosurgerybased arteriovenous malformation score and the modified Spetzler-Martin grading system to predict radiosurgical outcome. J Neurosurg 103: 642-648, 2005. 2. Colombo F, Cavedon C, Casentini L, Francescon P, Causin F, Pinna V: Early results of CyberKnife radiosurgery for arteriovenous malformations. J Neurosurg 111:807-819, 2009. 3. Davidson AS, Morgan MK: How safe is arteriovenous malformation surgery? A prospective,
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von Kummer R, Biondi A, Berkefeld J, Klijn CJM, Harkness K, Libman R, Barreau X, Moskowitz AJ; for the international ARUBA investigators: Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial. Lancet 2013. 13. O’Connor TE, Friedman WA: Magnetic resonance imaging assessment of cerebral arteriovenous malformation obliteration after stereotactic radiosurgery. Neurosurgery 73:761-766, 2013. 14. Ogilivy CS, Stieg PE, Awad I, Brown RD Jr, Kondziolka D, Rosenwasser R, Young WL, Hademenos G: AHA scientific statement: recommendations for the management of intracranial arteriovenous malformations: a statement for health-care professionals from a special writing group of the Stroke Council, American Stroke Association. Stroke 32:1458-1471, 2001. 15. Pollock BE, Brown RD Jr: Use of the Modified Rankin Scale to assess outcome after arteriovenous malformation radiosurgery. Neurology 67: 1630-1634, 2006. 16. Pollock BE, Flickinger JC: A proposed radiosurgery-based grading system for arteriovenous malformations. J Neurosurg 96:79-85, 2002. 17. Pollock BE, Flickinger JC: Modification of the radiosurgery-based arteriovenous malformation grading system. Neurosurgery 63:239-243, 2008. 18. Pollock BE, Kondziolka D, Flickinger JC, Patel AK, Bissonette DJ, Lunsford LD: Magnetic resonance imaging: an accurate method to evaluate arteriovenous malformations after stereotactic radiosurgery. J Neurosurg 85:1044-1049, 1996. 19. Pollock BE, Link MJ, Brown RD Jr: The risk of stroke or clinical impairment after stereotactic radiosurgery for ARUBA-eligible patients. Stroke 44:437e441. 20. Raffa SJ, Chi YY, Bova FJ, Friedman WA: Validation of the radiosurgery-based arteriovenous malformation score in a large linear accelerator radiosurgery experience. J Neurosurg 111:832-839, 2009.
21. Saatci I, Geyik S, Yav K, Cekirge HS: Endovascular treatment of brain arteriovenous malformations with prolonged intranidal Onyx injection technique: long-term results in 350 consecutive patients with completed endovascular treatment course. J Neurosurg 383:614-621, 2011. 22. Sheehan JP: Comment on Pollock BE, Flickinger JC. Modification of the radiosurgery-based arteriovenous malformation grading system. Neurosurgery 63:243, 2008. 23. Spetzler RF, Martin NA: A proposed grading system for arteriovenous malformations. J Neurosurg 65:476-483, 1986. 24. Spetzler RF, Ponce FA: A 3-tier classification of cerebral arteriovenous malformations. J Neurosurg 114:842-849, 2011. 25. van Beijnum J, van der Worp HB, Buis DR, AlShahi Salman R, Kappelle LJ, Rinkel GJ, van der Sprenkel JWB, Vandertop WP, Algra A, Klijn CJM: Treatment of brain arteriovenous malformations: a systematic review and meta-analysis. JAMA 306: 2011-2019, 2011. 26. Wong GK, Kam MK, Chiu SK, Lam JM, Leung CH, Ng DW, Ngar YK, Poon WS: Validation of the modified radiosurgery-based arteriovenous malformation score in a linear accelerator radiosurgery experience in Hong Kong. J Clin Neurosci 19:1252-1254, 2012.
Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Received 2 January 2014; accepted 8 July 2014 Citation: World Neurosurg. (2014). http://dx.doi.org/10.1016/j.wneu.2014.07.009 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2014 Elsevier Inc. All rights reserved.
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