Radiosurgery vs lobectomy for temporal lobe epilepsy: Phase 3 Clinical Trial

描述（由申请人提供）：据估计，0.5%-1.0%的美国人口患有癫痫，20%的癫痫患者患有医学难治性癫痫发作。单侧颞叶癫痫发作的患者在颞叶切除术后有很好的机会消除癫痫。基于一项初步临床试验的成功完成，该试验显示无复发率超过80%，且毒性可接受，因此采用放射外科或颞叶切除术治疗精心选择的患者是平衡的。本研究的目的是比较放射外科与颞叶切除术治疗药物耐药性颞叶癫痫患者的有效性，包括癫痫发作的自由度、癫痫发作减少、神经心理学结局、生活质量和成本效益。目标1：比较伽玛刀放射外科（GKS）与开放式颞叶切除术治疗耐药性颞叶癫痫患者的无复发结局和发病率。我们的主要假设是，放射外科和肺叶切除术在治疗后25-36个月的无癫痫发生率相当（从治疗后2年开始的1年无癫痫发作）。如果单侧95%置信区间排除了无并发症率降低15%，则认为两组等效。我们的次要假设是，放射外科手术将导致癫痫发作与基线相比显著减少，并且到治疗后2年，这两种治疗的癫痫发作减少百分比相同。目标二：比较接受放射外科手术和颞叶手术的患者的神经心理学结局，特别是语言优势半球治疗患者的言语记忆功能。我们的假设是，接受颞叶切除术治疗的言语主导型颞叶癫痫患者的言语记忆会显著降低，而接受放射外科治疗的患者的言语记忆不会显著降低。目标3：确定与开放手术相比，放射外科治疗后颞叶癫痫患者的生活质量发生了哪些变化。我们的主要假设是两组的生活质量指标都将有所改善（与治疗后3年相比）。我们的次要假设是，开放手术和放射外科受试者在治疗后第一年内都会出现治疗效应引起的生活质量指标一过性降低，但无并发症的受试者的生活质量将得到改善，与治疗组无关。目的4：比较放射外科与开放手术的成本-效果。我们假设放射外科手术在患者的一生中比颞叶切除术更具成本效益。本研究的目的是比较两种方法的治疗符合癫痫：标准的前颞叶切除术与非侵入性伽玛刀治疗。除了主要的结果，即患者的数量，使无脊椎动物，我们将比较保留的语言功能，生活质量的措施，和治疗费用。 公共卫生相关性：抗药性癫痫是一个重要的健康问题，需要新的治疗方法。本研究旨在比较传统手术（颞叶切除术）与伽玛刀放射外科治疗颞叶癫痫患者的新技术。这种疗法将提供一种非侵入性的方法来解决这个问题，并可能降低发病率（手术并发症，语言功能下降）。该研究旨在表明，这种疗法将提高癫痫患者的生活质量，减少并发症并节省费用。

DESCRIPTION (provided by applicant): It is estimated that 0.5%-1.0% of the U.S. population has epilepsy, and that 20% of patients with epilepsy have medically refractory seizures. Patients with unilateral temporal lobe seizure onsets have an excellent chance of becoming seizure-free following temporal lobectomy. Based on the successful completion of a Pilot Clinical Trial showing that seizure-free rates were in excess of 80% and with acceptable toxicity, there is equipoise for treating well-selected patients with either radiosurgery or temporal resection. The purpose of this study is to compare the effectiveness of radiosurgery with temporal lobectomy in the treatment of patients with pharmaco-resistant temporal lobe epilepsy including freedom from seizures, seizure reduction, neuropsychological outcomes, quality of life and cost-effectiveness. Aim 1: To compare the seizure-free outcomes and morbidity of Gamma Knife radiosurgery (GKS) for patients with pharmaco-resistant temporal lobe epilepsy with those of open temporal lobectomy. Our primary hypothesis is that radiosurgery and lobectomy will have equivalent seizure-free rates at 25-36 months following therapy (one-year of seizure freedom beginning 2 years after treatment). The two arms will be considered equivalent if a one-sided 95% confidence interval precludes a decrease in seizure-free rate of 15%. Our secondary hypothesis is that radiosurgery will result in significant reductions in seizures compared to baseline and that by 2 years following treatment the percentage reduction in seizures will be identical for these two treatments. Aim 2: To compare the neuropsychological outcomes in patients undergoing radiosurgery and temporal lobe surgery, in particular with respect to verbal memory function for language-dominant hemisphere treated patients. Our hypothesis is that patients treated for speech-dominant temporal lobe seizures with temporal lobectomy will show significant reductions in verbal memory and those patients treated with radiosurgery will not have significant reduction in measures of verbal memory. Aim 3: To determine what changes occur in the quality of life of patients with temporal lobe epilepsy following radiosurgical treatment as compared with open surgery. Our primary hypothesis is that there will be improvements (comparing baseline with 3 years post- treatment) in quality of life measures in both groups. Our secondary hypothesis is that both open surgery and radiosurgery subjects will undergo transient reductions in quality of life measures caused by treatment effects during the first year following treatment, but that quality of life will improve for subjects who become seizure-free, independent of treatment group. Aim 4: To compare the cost-effectiveness of radiosurgery compared with open surgery. We hypothesize that radiosurgery will be cost-effective compared to temporal lobectomy over the lifetime of the patient. The purpose of this study is to compare two methods of treatment of surgically-amenable epilepsy: standard anterior temporal lobectomy versus noninvasive Gamma Knife radiosurgery. Beyond the main outcome of the number of patients rendered seizure-free, we will compare preservation of language functions, quality of life measures, and the cost of treatment. PUBLIC HEALTH RELEVANCE: Pharmaco-resistant epilepsy is a significant health problem for which new therapies are needed. This study is designed to compare traditional surgery (temporal lobectomy) with the novel technique of Gamma Knife radiosurgery in the treatment of patients with temporal lobe epilepsy. This therapy would offer a non-invasive approach to this problem with potential reduction in morbidity (surgical complications, reduced language function). The study is designed to show that this therapy will improve quality of life for patients with epilepsy with reduced complications and cost-savings.