[en] PURPOSE: The relationship of dose and volume to arteriovenous malformation (AVM) obliteration, complications, and hemorrhage is not well defined for large AVMs. Multivariate analysis was performed to assess the relationship of multiple factors to the outcome of a series of AVMs significantly larger than previously reported in the literature. MATERIALS and METHODS: Between 1988 and 1991, 73 patients with intracranial AVMs were treated with LINAC based radiosurgery. The median treatment volume was 8 cc (range 0.4 - 143 cc). 40% of the AVMs were larger than 15 cc. The median equivalent diameter of the treatment volumes was 2.5 cm (range 0.9 - 6.8 cm). The median Spetzler-Martin grade was III. The median number of treatment isocenters was 2 (range 1 - 7) and the median prescription isodose line (normalized to the maximum dose) was 66% (range 23 - 90%). The median minimum and maximum AVM doses were 1600 cGy (range 1000 - 2200 cGy) and 2518 cGy (range 1745 - 4652 cGy) respectively. RESULTS: Clinical follow-up was available for all patients and radiologic follow-up was available for 98% of living patients. At 5 years, 27 patients (37%) had complete AVM obliteration documented by either angiogram or MRI/MRA, 7 (10%) were retreated with radiosurgery, 2 (3%) underwent surgical resection, 5 (7%) died of intracranial hemorrhage, and 4 (5%) died of intercurrent disease. The median follow-up for the remaining 28 patients (38%) who did not reach one of these endpoints was 71 months. The 5 year actuarial radiographic obliteration rate was 46%. Angiograms were obtained when a MRI suggested obliteration or at the time of retreatment. The 5 year angiographic obliteration rate in these selected patients was 63%. Fifty-two percent of patients had AVM obliteration documented after 3 years. For AVMs <1 cc, 1-5 cc, 5-15 cc, and >15 cc, the 5 year radiographic obliteration rates were 81%, 62%, 47% and 27%. The mean doses for the groups were 1834, 1763, 1660, and 1519 cGy. In multivariate analysis, AVM obliteration was significantly associated with minimum dose and negatively associated with a history of prior embolization. Volume was statistically significant in univariate but not multivariate analysis. The 5 year actuarial rate of developing post-radiosurgical MRI T2 changes was 52% with a median time to detection of 12 months. Forty-eight percent of patients with these MRI abnormalities had clinically significant symptoms and 18% required medical intervention. There were 4 cases (5%) of radiation necrosis requiring surgical resection including 1 fatality (1%). In multivariate analysis, equivalent treatment diameter and K-index were statistically significant. Nine patients (12%) suffered clinically significant hemorrhages, 5 of which were fatal. Following radiosurgery, the annualized rate of hemorrhage was 3-5% per person-year and the annualized mortality rate from hemorrhage was 2-3% per person-year. These rates were consistent with those calculated using the Kaplan-Meier life table method. The median time to first hemorrhage following radiosurgery was 31 months (range 11 - 73 months). In multivariate analysis, post-treatment hemorrhage was significantly associated with treatment volume, number of prior hemorrhages, and venous restrictive disease. CONCLUSION: The low rate of AVM obliteration for this series compared to other series in the literature may be attributed to the inclusion of non-angiographic failures in the reported obliteration rate, the large size of AVMs, the moderate doses prescribed, and possibly the high incidence of prior embolization procedures (59%). Reports of AVM obliteration rates should include non-angiographic MRI/MRA failures. With long follow-up, a significant rate of late obliteration and a higher than expected rate of post-radiosurgical hemorrhage were observed. AVM obliteration was associated with minimum AVM dose and negatively associated with a history of prior embolization. Complications were associated with equivalent treatment diameter and K-index. Post-radiosurgery hemorrhage was associated with treatment volume, number of prior hemorrhages, and venous restrictive disease. Large AVMs are problematic as they are associated with low obliteration rates (27% for AVM > 20 cc), higher complication rates, and higher rates of post-radiosurgery hemorrhage

[en] Purpose: For radiosurgery of large arteriovenous malformations (AVMs), the optimal relationship of dose and volume to obliteration, complications, and hemorrhage is not well defined. Multivariate analysis was performed to assess the relationship of multiple AVM and treatment factors to the outcome of AVMs significantly larger than previously reported in the literature. Methods and Materials: 73 patients with intracranial AVMs underwent LINAC radiosurgery. Over 50% of the AVMs were larger than 3 cm in diameter and the median and mean treatment volumes were 8.4 cc and 15.3 cc, respectively (range 0.4-143.4 cc). Minimum AVM treatment doses varied between 1000-2200 cGy (median: 1600 cGy). Results: The obliteration rates for treatment volumes < 4 cc, 4-13.9 cc, and ≥ 14 cc were 67%, 58%, and 23%, respectively. AVM obliteration was significantly associated with higher minimum treatment dose and negatively associated with a history of prior embolization with particulate materials. No AVM receiving < 1400 cGy was obliterated. The incidence of post-radiosurgical imaging abnormalities and clinical complications rose with increasing treatment volume. For treatment volumes > 14 cc receiving ≥ 1600 cGy, the incidence of post-radiosurgical MRI T2 abnormalities was 72% and the incidence of radiation necrosis requiring resection was 22%. The rate of post-radiosurgical hemorrhage was 2.7% per person-year for AVMs with treatment volumes < 14 cc and 7.5% per person-year for AVMs ≥ 14 cc. Conclusion: As AVM size increases, the dose-volume range for the optimal balance between successful obliteration and the risk of complications and post-radiosurgical hemorrhage narrows

[en] Purpose: To better understand radiation complications of arteriovenous malformation (AVM) radiosurgery and factors affecting their resolution. Methods and Materials: AVM patients (102/1255) who developed neurological sequelae after radiosurgery were studied. The median AVM marginal dose (D_min) was 19 Gy (range: 10-35). The median volume was 5.7 cc (range: 0.26-143). Median follow-up was 34 months (range: 9-140). Results: Complications consisted of 80/102 patients with evidence of radiation injury to the brain parenchyma (7 also with cranial nerve deficits, 12 also with seizures, 5 with cyst formation), 12/102 patients with isolated cranial neuropathies, and 10/102 patients with only new or worsened seizures. Severity was classified as minimal in 39 patients, mild in 40, disabling in 21, and fatal in 2 patients. Symptoms resolved completely in 42 patients for an actuarial resolution rate of 54% ± 7% at 3 years post-onset. Multivariate analysis identified significantly greater symptom resolution in patients with no prior history of hemorrhage (p = 0.01, 66% vs. 41%), and in patients with symptoms of minimal severity: headache or seizure as the only sequelae of radiosurgery (p < 0.0001, 88% vs. 34%). Conclusion: Late sequelae of radiosurgery manifest in varied ways. Further long-term studies of these problems are needed that take into account symptom severity and prior hemorrhage history