BACKGROUND Optimal treatment paradigm for large arteriovenous malformations (AVMs) is controversial. Volume-staged stereotactic radiosurgery (VS-SRS) provides an effective option for these high-risk lesions, but optimizing treatment for these recalcitrant and rare lesions has proven difficult. METHODS This is a multi-centered retrospective review of patients treated with a planned prospective volume staging approach to stereotactically treat the entire nidus of an AVM with volume stages separated by intervals of 3-6 months. A total of 9 radiosurgical centers treated 257 patients with VS-SRS between 1991 and 2016. We evaluated near complete response (nCR), obliteration, cure, and overall survival. RESULTS With a median age of 33 years old at the time of first SRS volume stage, patients received 2-4 total volume stages and a median follow up of 5.7 years after VS-SRS. The median total AVM nidus volume was 23.25 cc (range: 7.7-94.4 cc) with a median margin dose per stage of 17 Gy (range: 12-20 Gy). Total AVM volume, margin dose per stage, compact nidus, lack of prior embolization, and lack of thalamic location involvement were all associated with improved outcomes. Dose >/= 17.5 Gy was strongly associated with improved rates of nCR, obliteration, and cure. With dose >/= 17.5 Gy, 5- and 10-year cure rates were 33.7% and 76.8% in evaluable patients compared to 23.7% and 34.7% of patients with 17 Gy and 6.4% and 20.6% with <17 Gy per volume-stage (p = 0.004). Obliteration rates in diffuse nidus architecture with <17 Gy were particularly poor with none achieving obliteration compared to 32.3% with doses >/= 17 Gy at 5 years (p = 0.007). Comparatively, lesions with a compact nidus architecture exhibited obliteration rates at 5 years were 10.7% vs 9.3% vs 26.6% for dose >17 Gy vs 17 Gy vs >/=17.5 Gy. CONCLUSION VS-SRS is an option for upfront treatment of large AVMs. Higher dose was associated with improved rates of nCR, obliteration, and cure suggesting that larger volumetric responses may facilitate salvage therapy and optimize the chance for cure.

中文翻译：

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大动静脉畸形体积分期放射外科的剂量反应和结构：一项多机构研究

背景 大动静脉畸形 (AVM) 的最佳治疗范式是有争议的。体积分期立体定向放射外科 (VS-SRS) 为这些高危病变提供了有效的选择，但已证明对这些顽固和罕见病变的优化治疗很困难。方法 这是一项多中心回顾性研究，对采用计划的前瞻性容量分期方法对 AVM 的整个病灶进行立体定向治疗，容量分期间隔 3-6 个月。1991 年至 2016 年间，共有 9 个放射外科中心治疗了 257 名 VS-SRS 患者。我们评估了接近完全缓解 (nCR)、闭塞、治愈和总生存期。结果 第一个 SRS 体积分期时的中位年龄为 33 岁，患者接受了 2-4 个总体积分期，中位随访时间为 5 次。VS-SRS 后 7 年。中位总 AVM 病灶体积为 23.25 cc（范围：7.7-94.4 cc），每个阶段的中位边缘剂量为 17 Gy（范围：12-20 Gy）。总 AVM 体积、每个阶段的边缘剂量、紧凑的病灶、没有预先栓塞和没有丘脑位置受累都与改善的结果相关。剂量 >/= 17.5 Gy 与 nCR、闭塞和治愈率的提高密切相关。剂量 >/= 17.5 Gy 时，可评估患者的 5 年和 10 年治愈率分别为 33.7% 和 76.8%，相比之下，17 Gy 的患者为 23.7% 和 34.7%，而 <17 Gy 的患者为 6.4% 和 20.6% -阶段（p = 0.004）。弥散病灶结构中 <17 Gy 的闭塞率特别低，5 年时剂量 >/= 17 Gy 时为 32.3%（p = 0.007），没有实现闭塞。比较，具有致密病灶结构的病灶在 5 年时的闭塞率分别为 10.7% vs 9.3% vs 26.6%，剂量 >17 Gy vs 17 Gy vs >/=17.5 Gy。结论 VS-SRS 是大型 AVM 前期治疗的一种选择。更高的剂量与 nCR、闭塞和治愈率的提高相关，这表明更大的容量反应可能有助于挽救治疗并优化治愈的机会。