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治疗前[18F]-FET-PET的纹理分析及其与高级别胶质瘤肿瘤分级和患者生存的相关性

Textural analysis of pre-therapeutic [18F]-FET-PET and its correlation with tumor grade and patient survival in high-grade gliomas.

作者信息

Pyka Thomas, Gempt Jens, Hiob Daniela, Ringel Florian, Schlegel Jürgen, Bette Stefanie, Wester Hans-Jürgen, Meyer Bernhard, Förster Stefan

机构信息

Department of Nuclear Medicine, Klinikum Rechts der Isar der TU München, Ismaninger Str., Munich, Germany.

Neurosurgic Department, Klinikum Rechts der Isar der TU München, Ismaninger Str., Munich, Germany.

出版信息

Eur J Nucl Med Mol Imaging. 2016 Jan;43(1):133-141. doi: 10.1007/s00259-015-3140-4. Epub 2015 Jul 29.

Abstract

PURPOSE

Amino acid positron emission tomography (PET) with [18F]-fluoroethyl-L-tyrosine (FET) is well established in the diagnostic work-up of malignant brain tumors. Analysis of FET-PET data using tumor-to-background ratios (TBR) has been shown to be highly valuable for the detection of viable hypermetabolic brain tumor tissue; however, it has not proven equally useful for tumor grading. Recently, textural features in 18-fluorodeoxyglucose-PET have been proposed as a method to quantify the heterogeneity of glucose metabolism in a variety of tumor entities. Herein we evaluate whether textural FET-PET features are of utility for grading and prognostication in patients with high-grade gliomas.

METHODS

One hundred thirteen patients (70 men, 43 women) with histologically proven high-grade gliomas were included in this retrospective study. All patients received static FET-PET scans prior to first-line therapy. TBR (max and mean), volumetric parameters and textural parameters based on gray-level neighborhood difference matrices were derived from static FET-PET images. Receiver operating characteristic (ROC) and discriminant function analyses were used to assess the value for tumor grading. Kaplan-Meier curves and univariate and multivariate Cox regression were employed for analysis of progression-free and overall survival.

RESULTS

All FET-PET textural parameters showed the ability to differentiate between World Health Organization (WHO) grade III and IV tumors (p < 0.001; AUC 0.775). Further improvement in discriminatory power was possible through a combination of texture and metabolic tumor volume, classifying 85 % of tumors correctly (AUC 0.830). TBR and volumetric parameters alone were correlated with tumor grade, but showed lower AUC values (0.644 and 0.710, respectively). Furthermore, a correlation of FET-PET texture but not TBR was shown with patient PFS and OS, proving significant in multivariate analysis as well. Volumetric parameters were predictive for OS, but this correlation did not hold in multivariate analysis.

CONCLUSIONS

Determination of uptake heterogeneity in pre-therapeutic FET-PET using textural features proved valuable for the (sub-)grading of high-grade glioma as well as prediction of tumor progression and patient survival, and showed improved performance compared to standard parameters such as TBR and tumor volume. Our results underscore the importance of intratumoral heterogeneity in the biology of high-grade glial cell tumors and may contribute to individual therapy planning in the future, although they must be confirmed in prospective studies before incorporation into clinical routine.

摘要

目的

[¹⁸F]-氟乙基-L-酪氨酸(FET)氨基酸正电子发射断层扫描(PET)在恶性脑肿瘤的诊断检查中已得到广泛应用。利用肿瘤与本底比值(TBR)分析FET-PET数据对于检测存活的高代谢脑肿瘤组织具有很高的价值;然而,它在肿瘤分级方面尚未被证明同样有用。最近,18-氟脱氧葡萄糖-PET中的纹理特征已被提议作为一种量化多种肿瘤实体中葡萄糖代谢异质性的方法。在此,我们评估纹理FET-PET特征在高级别胶质瘤患者的分级和预后评估中是否有用。

方法

本回顾性研究纳入了113例经组织学证实为高级别胶质瘤的患者(70例男性,43例女性)。所有患者在一线治疗前均接受了静态FET-PET扫描。基于灰度邻域差异矩阵的TBR(最大值和平均值)、体积参数和纹理参数均从静态FET-PET图像中得出。采用受试者操作特征(ROC)和判别函数分析来评估肿瘤分级的价值。采用Kaplan-Meier曲线以及单因素和多因素Cox回归分析无进展生存期和总生存期。

结果

所有FET-PET纹理参数均显示出区分世界卫生组织(WHO)III级和IV级肿瘤的能力(p<0.001;AUC为0.775)。通过结合纹理和代谢肿瘤体积,鉴别能力可进一步提高,能正确分类85%的肿瘤(AUC为0.830)。单独的TBR和体积参数与肿瘤分级相关,但AUC值较低(分别为0.644和0.710)。此外,FET-PET纹理而非TBR与患者的无进展生存期和总生存期相关,在多因素分析中也具有显著性。体积参数对总生存期有预测作用,但在多因素分析中这种相关性不成立。

结论

利用纹理特征确定治疗前FET-PET中的摄取异质性对于高级别胶质瘤的(亚)分级以及肿瘤进展和患者生存预测具有重要价值,并且与TBR和肿瘤体积等标准参数相比表现更优。我们的结果强调了肿瘤内异质性在高级别胶质细胞瘤生物学中的重要性,尽管在纳入临床常规之前必须在前瞻性研究中得到证实,但可能有助于未来的个体化治疗规划。

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