1Department of Neurosurgical Oncology, Barrow Brain Tumor Research Center, St. Joseph's Hospital and Medical Center, Phoenix.
2Division of Biostatistics, Arizona State University, Tempe; and.
J Neurosurg. 2018 Apr;128(4):1084-1090. doi: 10.3171/2016.12.JNS161682. Epub 2017 May 26.
OBJECTIVE Seizures are the most common presenting symptom of newly diagnosed WHO Grade II gliomas (low-grade glioma [LGG]) and significantly impair quality of life. Although gross-total resection of LGG is associated with better seizure control, it remains unclear whether an extent of resection (EOR) "threshold" exists for long-term seizure control. Specifically, what proportion of FLAIR-positive tissue in patients with newly diagnosed LGG must be removed to achieve Engel Class I seizure freedom? To clarify the EOR threshold for long-term seizure control, the authors analyzed data from a consecutive series of patients with newly diagnosed LGG who presented with seizures and subsequently underwent microsurgical resection. METHODS The authors identified consecutive patients with newly diagnosed LGG who presented with seizures and were treated at the Barrow Neurological Institute between 2002 and 2012. Patients were dichotomized into those who were seizure free postoperatively and those who were not. The EOR was calculated by quantitative comparison of pre- and postoperative MRI. Univariate analysis of these 2 groups included the chi-square test and the Mann-Whitney U-test, and a multivariate logistic regression was constructed to predict the impact of multiple independent variables on the likelihood of postoperative seizure freedom. To determine a threshold of EOR that optimizes seizure freedom, a receiver operating characteristic curve was plotted and the optimal point of discrimination was determined. RESULTS Data from 128 patients were analyzed (male/female ratio 1.37:1; mean age 40.8 years). All 128 patients presented with seizures, usually generalized (n = 57, 44.5%) or simple partial (n = 57, 44.5%). The median EOR was 90.0%. Of 128 patients, 46 (35.9%) had 100% volumetric tumor resection, 64 (50.0%) had 90%-99% volumetric tumor resection, and 11 (8.6%) had 80%-89% volumetric tumor resection. Postoperatively, 105 (82%) patients were seizure free (Engel Class I); 23 (18%) were not (Engel Classes II-IV). The proportion of seizure-free patients increased in proportion to the EOR. Predictive variables included in the regression model were preoperative Karnofsky Performance Scale score, seizure type, time from diagnosis to surgery, preoperative number of antiepileptic drugs, and EOR. Only EOR significantly affected the likelihood of postoperative Engel Class I status (OR 11.5, 95% CI 2.4-55.6; p = 0.002). The receiver operating characteristic curve generated based on Engel Class I status showed a sensitivity of 0.65 and 1 - specificity of 0.175, corresponding to an EOR of 80%. CONCLUSIONS For adult patients with LGG who suffer seizures, the results suggest that seizure freedom can be attained when EOR > 80% is achieved. Improvements in both the proportion of seizure-free patients and the durability of seizure freedom were observed beyond this 80% threshold. Interestingly, this putative EOR seizure-freedom threshold closely approximates that reported for the overall survival benefit in newly diagnosed hemispheric LGGs, suggesting that a minimum level of residual tumor burden is necessary for both disease and symptomatic progression.
癫痫发作是新诊断的世界卫生组织(WHO)二级胶质瘤(低级别胶质瘤 [LGG])最常见的首发症状,严重影响生活质量。尽管 LGG 的大体全切除与更好的癫痫控制相关,但仍不清楚是否存在长期癫痫控制的切除范围(EOR)“阈值”。具体来说,新诊断的 LGG 患者中必须切除多少比例的 FLAIR 阳性组织才能实现 Engel 分级 I 无癫痫发作?为了阐明长期癫痫控制的 EOR 阈值,作者分析了连续系列新诊断为 LGG 且伴有癫痫发作并随后接受显微镜下切除术的患者的数据。
作者确定了在 2002 年至 2012 年期间在巴罗神经研究所就诊的新诊断为 LGG 且伴有癫痫发作的连续患者。将患者分为术后无癫痫发作和有癫痫发作的两组。通过术前和术后 MRI 的定量比较计算 EOR。对这两组进行单变量分析,包括卡方检验和曼-惠特尼 U 检验,并构建多元逻辑回归模型来预测多个独立变量对术后无癫痫发作可能性的影响。为了确定优化癫痫无发作的 EOR 阈值,绘制了受试者工作特征曲线并确定了最佳的区分点。
分析了 128 名患者的数据(男女比例 1.37:1;平均年龄 40.8 岁)。所有 128 名患者均出现癫痫发作,通常为全身性(n = 57,44.5%)或简单部分性(n = 57,44.5%)。中位 EOR 为 90.0%。在 128 名患者中,46 名(35.9%)进行了 100%肿瘤体积切除术,64 名(50.0%)进行了 90%-99%肿瘤体积切除术,11 名(8.6%)进行了 80%-89%肿瘤体积切除术。术后,105 名(82%)患者无癫痫发作(Engel 分级 I);23 名(18%)有癫痫发作(Engel 分级 II-IV)。无癫痫发作患者的比例与 EOR 成正比增加。纳入回归模型的预测变量包括术前卡诺夫斯基表现量表评分、癫痫发作类型、从诊断到手术的时间、术前抗癫痫药物数量和 EOR。只有 EOR 显著影响术后 Engel 分级 I 状态的可能性(OR 11.5,95%CI 2.4-55.6;p = 0.002)。基于 Engel 分级 I 状态生成的受试者工作特征曲线显示敏感性为 0.65,1-特异性为 0.175,对应的 EOR 为 80%。
对于患有癫痫发作的 LGG 成年患者,结果表明当 EOR > 80%时可实现无癫痫发作。超过这 80%的阈值,观察到无癫痫发作患者的比例和癫痫无发作的持久性均有所提高。有趣的是,这个推测的 EOR 无癫痫发作阈值与新诊断的大脑半球 LGG 的总生存获益报告的阈值非常接近,这表明对于疾病和症状进展,均需要有最低水平的残留肿瘤负担。