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

描述（由申请人提供）：据估计，美国有0.5%-1.0%的人口患有癫痫，20%的癫痫患者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很有可能不再发作。根据成功完成的一项临床试验表明，癫痫无发作率超过80%，并且毒性可接受，因此，选择合适的患者进行放射手术或颞叶切除治疗是平衡的。本研究的目的是比较放射手术与颞叶切除术治疗药物抵抗性颞叶癫痫患者的有效性，包括癫痫发作的自由、癫痫发作的减少、神经心理结果、生活质量和成本效益。目的1：比较伽玛刀放射治疗（GKS）与开放颞叶切除术治疗耐药颞叶癫痫患者的无癫痫发作结局和发病率。我们的主要假设是放射手术和肺叶切除术在治疗后25-36个月的无癫痫发生率相等（治疗后2年开始的一年无癫痫发作）。如果单侧95%置信区间排除了15%的无癫痫发作率下降，则认为两个组是等效的。我们的第二个假设是，与基线相比，放射手术将导致癫痫发作的显著减少，并且在治疗后2年，两种治疗的癫痫发作减少百分比将相同。目的2：比较接受放射手术和颞叶手术的患者的神经心理学结果，特别是在语言优势半球治疗患者的言语记忆功能方面。我们的假设是，接受颞叶切除治疗的言语主导型颞叶癫痫患者的言语记忆能力显著下降，而接受放射手术治疗的患者的言语记忆能力不会显著下降。目的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什么变化。我们的主要假设是两组患者的生活质量都有改善（与治疗后3年的基线比较）。我们的第二个假设是，开放手术和放射手术的受试者在治疗后的第一年都会因治疗效果而出现短暂的生活质量下降，但独立于治疗组，无癫痫发作的受试者的生活质量会得到改善。目的4：比较放射手术与开放手术的成本-效果。我们假设在患者的一生中，放射手术将比颞叶切除术更具成本效益。本研究的目的是比较两种治疗手术可适应癫痫的方法：标准颞叶前部切除术与非侵入性伽玛刀放射手术。除了癫痫无发作的主要结果外，我们还将比较语言功能的保存、生活质量措施和治疗费用。

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.