Surgery for Glioblastoma: Impact of the Combined Use of 5-Aminolevulinic Acid and Intraoperative MRI on Extent of Resection and Survival.
Surgery for Glioblastoma: Impact of the Combined Use of 5-Aminolevulinic Acid and Intraoperative MRI on Extent of Resection and Survival.
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DOI：
10.1371/journal.pone.0131872
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
König R
中科院分区：
文献类型：
--
作者：
Coburger J;Hagel V;Wirtz CR;König R
越来越多的证据表明，在胶质母细胞瘤（GBM）手术中，切除范围（EoR）的增加导致患者生存率的增加。基于组织病理学评估，肿瘤描述的Gd-DTPA增强和5-氨基酮戊酸荧光（5-ALA）可能是协同的术中切除控制。评估GBM术中MRI（iMRI）辅助手术中额外使用5-ALA对切除范围（EoR）、无进展生存期（PFS）和总生存期（OS）的影响。我们前瞻性招募了33例符合大体全切除（GTR）条件的GBM患者，并使用5-ALA和iMRI进行了联合手术。作为对照组，我们基于144例iMRI辅助手术患者进行了回顾性配对评估。匹配标准为MGMT启动子甲基化、复发手术、功能区位置、肿瘤大小和年龄。仅纳入预期GTR和原发性GBM的患者。我们使用对数秩检验计算Kaplan Mayer估计值以比较OS和PFS。我们使用T检验比较EoR的体积结果，使用卡方检验比较两组之间的新发永久性神经功能缺损（nPND）和一般并发症。中位随访时间为31个月。在匹配标准方面，两组之间没有发现显著差异。与单独的iMRI（82%）相比，使用5-ALA和iMRI（100%）显著更经常（p <0.010）实现GTR。5-ALA和iMRI组的平均EoR（99.7%）显著（p<0.004）高于单独iMRI组（97.4%）。两组之间的并发症发生率无显著差异（iMRI组21%，5-ALA和iMRI组27%，p<0.518）。两组nPND均为6%。中位PFS（分别为6个月; p<0.309）和中位OS（iMRI：17个月;5-ALA和iMRI组：18个月;p<0.708））在两组之间无显著差异。我们发现，与单独使用iMRI相比，当组合5-ALA和iMRI时，EoR显著增加。如果在功能区病变中使用神经生理监测，最大化EoR不会导致并发症或神经功能缺损增加。EoR的进一步增加是否有利于患者的无进展生存期和总生存期，目前尚不能得出最终结论。
There is rising evidence that in glioblastoma(GBM) surgery an increase of extent of resection(EoR) leads to an increase of patient’s survival. Based on histopathological assessments tumor depiction of Gd-DTPA enhancement and 5-aminolevulinic-acid-fluorescence(5-ALA) might be synergistic for intraoperative resection control. To assess impact of additional use of 5-ALA in intraoperative MRI(iMRI) assisted surgery of GBMs on extent of resection(EoR), progression free survival(PFS) and overall survival(OS). We prospectively enrolled 33 patients with GBMs eligible for gross-total-resection(GTR) and performed a combined approach using 5-ALA and iMRI. As a control group, we performed a retrospective matched pair assessment, based on 144 patients with iMRI-assisted surgery. Matching criteria were, MGMT promotor methylation, recurrent surgery, eloquent location, tumor size and age. Only patients with an intended GTR and primary GBMs were included. We calculated Kaplan Mayer estimates to compare OS and PFS using the Log-Rank-Test. We used the T-test to compare volumetric results of EoR and the Chi-Square-Test to compare new permanent neurological deficits(nPND) and general complications between the two groups. Median follow up was 31 months. No significant differences between both groups were found concerning the matching criteria. GTR was achieved significantly more often (p <0.010) using 5-ALA&iMRI (100%) compared to iMRI alone(82%). Mean EoR was significantly(p<0.004) higher in 5-ALA&iMRI-group(99.7%) than in iMRI-alone-group(97.4%) Rate of complications did not differ significantly between groups(21% iMRI-group,27%5-ALA&iMRI-group,p<0.518). nPND were found in 6% in both groups. Median PFS (6mo resp.;p<0.309) and median OS(iMRI:17mo;5-ALA&iMRI-group:18mo;p<0.708)) were not significantly different between both groups. We found a significant increase of EoR when combining 5-ALA&iMRI compared to use of iMRI alone. Maximizing EoR did not lead to an increase of complications or neurological deficits if used with neurophysiological monitoring in eloquent lesions. No final conclusion can be drawn whether a further increase of EoR benefits patient’s progression free survival and overall survival.
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