Division of Neurological Surgery.
J Neurosurg. 2014 Apr;120(4):846-53. doi: 10.3171/2013.12.JNS13184. Epub 2014 Jan 31.
Despite improvements in the medical and surgical management of patients with glioblastoma, tumor recurrence remains inevitable. For recurrent glioblastoma, however, the clinical value of a second resection remains uncertain. Specifically, what proportion of contrast-enhancing recurrent glioblastoma tissue must be removed to improve overall survival and what is the neurological cost of incremental resection beyond this threshold?
The authors identified 170 consecutive patients with recurrent supratentorial glioblastomas treated at the Barrow Neurological Institute from 2001 to 2011. All patients previously had a de novo glioblastoma and following their initial resection received standard temozolomide and fractionated radiotherapy.
The mean clinical follow-up was 22.6 months and no patient was lost to follow-up. At the time of recurrence, the median preoperative tumor volume was 26.1 cm(3). Following re-resection, median postoperative tumor volume was 3.1 cm(3), equating to an 87.4% extent of resection (EOR). The median overall survival was 19.0 months, with a median progression-free survival following re-resection of 5.2 months. Using Cox proportional hazards analysis, the variables of age, Karnofsky Performance Scale (KPS) score, and EOR were predictive of survival following repeat resection (p = 0.0001). Interestingly, a significant survival advantage was noted with as little as 80% EOR. Recursive partitioning analysis validated these findings and provided additional risk stratification at the highest levels of EOR. Overall, at 7 days after surgery, a deterioration in the NIH stroke scale score by 1 point or more was observed in 39.1% of patients with EOR ≥ 80% as compared with 16.7% for those with EOR < 80% (p = 0.0049). This disparity in neurological morbidity, however, did not endure beyond 30 days postoperatively (p = 0.1279).
For recurrent glioblastomas, an improvement in overall survival can be attained beyond an 80% EOR. This survival benefit must be balanced against the risk of neurological morbidity, which does increase with more aggressive cytoreduction, but only in the early postoperative period. Interestingly, this putative EOR threshold closely approximates that reported for newly diagnosed glioblastomas, suggesting that for a subset of patients, the survival benefit of microsurgical resection does not diminish despite biological progression.
尽管胶质母细胞瘤患者的医学和外科治疗有所改善,但肿瘤复发仍然不可避免。然而,对于复发性胶质母细胞瘤,再次切除的临床价值尚不确定。具体来说,需要切除多少比例的增强对比的复发性胶质母细胞瘤组织才能改善总体生存率,以及超过这个阈值的额外切除的神经学成本是多少?
作者从 2001 年至 2011 年在巴罗神经学研究所治疗的 170 例连续复发性幕上胶质母细胞瘤患者中确定了这一点。所有患者以前均患有新发胶质母细胞瘤,并且在初次切除后接受了标准的替莫唑胺和分割放射治疗。
平均临床随访时间为 22.6 个月,没有患者失访。在复发时,术前肿瘤体积中位数为 26.1cm3。再次切除后,肿瘤体积中位数为 3.1cm3,相当于 87.4%的切除范围(EOR)。中位总生存期为 19.0 个月,再次切除后的中位无进展生存期为 5.2 个月。使用 Cox 比例风险分析,年龄、卡诺夫斯基表现量表(KPS)评分和 EOR 等变量可预测再次切除后的生存(p=0.0001)。有趣的是,即使 EOR 仅为 80%,也可以观察到明显的生存优势。递归分区分析验证了这些发现,并在最高 EOR 水平提供了额外的风险分层。总的来说,在术后 7 天,EOR≥80%的患者中有 39.1%出现 NIH 中风量表评分恶化 1 分或以上,而 EOR<80%的患者有 16.7%(p=0.0049)。然而,这种神经发病率的差异在术后 30 天内并没有持续(p=0.1279)。
对于复发性胶质母细胞瘤,EOR 超过 80%可以提高总体生存率。这种生存获益必须与神经发病率的风险相平衡,而这种风险确实随着更积极的细胞减少而增加,但仅在术后早期。有趣的是,这个假定的 EOR 阈值与新诊断的胶质母细胞瘤报告的阈值非常接近,这表明对于一部分患者,尽管存在生物学进展,但手术切除的生存获益并没有降低。