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Published in: European Journal of Nuclear Medicine and Molecular Imaging 1/2016

01-01-2016 | Original Article

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

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

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 1/2016

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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.
Literature
1.
go back to reference Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114(2):97–109.PubMedCentralCrossRefPubMed Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114(2):97–109.PubMedCentralCrossRefPubMed
2.
go back to reference Viaccoz A, Lekoubou A, Ducray F. Chemotherapy in low-grade gliomas. Curr Opin Oncol. 2012;24(6):694–701.CrossRefPubMed Viaccoz A, Lekoubou A, Ducray F. Chemotherapy in low-grade gliomas. Curr Opin Oncol. 2012;24(6):694–701.CrossRefPubMed
3.
go back to reference Cloughesy T. The impact of recent data on the optimization of standards of care in newly diagnosed glioblastoma. Semin Oncol. 2011;38 Suppl 4:S11–20.CrossRefPubMed Cloughesy T. The impact of recent data on the optimization of standards of care in newly diagnosed glioblastoma. Semin Oncol. 2011;38 Suppl 4:S11–20.CrossRefPubMed
4.
go back to reference Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96.CrossRefPubMed Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96.CrossRefPubMed
5.
go back to reference Chaudhry NS, Shah AH, Ferraro N, Snelling BM, Bregy A, Madhavan K, et al. Predictors of long-term survival in patients with glioblastoma multiforme: advancements from the last quarter century. Cancer Investig. 2013;31(5):287–308.CrossRef Chaudhry NS, Shah AH, Ferraro N, Snelling BM, Bregy A, Madhavan K, et al. Predictors of long-term survival in patients with glioblastoma multiforme: advancements from the last quarter century. Cancer Investig. 2013;31(5):287–308.CrossRef
6.
go back to reference Weiler M, Wick W. Molecular predictors of outcome in low-grade glioma. Curr Opin Neurol. 2012;25(6):767–73.CrossRefPubMed Weiler M, Wick W. Molecular predictors of outcome in low-grade glioma. Curr Opin Neurol. 2012;25(6):767–73.CrossRefPubMed
7.
go back to reference Scott JN, Brasher PM, Sevick RJ, Rewcastle NB, Forsyth PA. How often are nonenhancing supratentorial gliomas malignant? A population study. Neurology. 2002;59(6):947–9.CrossRefPubMed Scott JN, Brasher PM, Sevick RJ, Rewcastle NB, Forsyth PA. How often are nonenhancing supratentorial gliomas malignant? A population study. Neurology. 2002;59(6):947–9.CrossRefPubMed
8.
go back to reference Gutman DA, Cooper LA, Hwang SN, Holder CA, Gao J, Aurora TD, et al. MR imaging predictors of molecular profile and survival: multi-institutional study of the TCGA glioblastoma data set. Radiology. 2013;267(2):560–9.PubMedCentralCrossRefPubMed Gutman DA, Cooper LA, Hwang SN, Holder CA, Gao J, Aurora TD, et al. MR imaging predictors of molecular profile and survival: multi-institutional study of the TCGA glioblastoma data set. Radiology. 2013;267(2):560–9.PubMedCentralCrossRefPubMed
9.
go back to reference Weckesser M, Langen K, Rickert C. al. e. O-(2-[(18)F]fluoroethyl)-L-tyrosine PET in the clinical evaluation of primary brain tumours. Eur J Nucl Med Mol Imaging. 2005;32:422–9.CrossRefPubMed Weckesser M, Langen K, Rickert C. al. e. O-(2-[(18)F]fluoroethyl)-L-tyrosine PET in the clinical evaluation of primary brain tumours. Eur J Nucl Med Mol Imaging. 2005;32:422–9.CrossRefPubMed
10.
go back to reference Dunet V, Rossier C, Buck A, Stupp R, Prior JO. Performance of 18F-fluoro-ethyl-tyrosine (18F-FET) PET for the differential diagnosis of primary brain tumor: a systematic review and metaanalysis. J Nucl Med. 2012;53(2):207–14.CrossRefPubMed Dunet V, Rossier C, Buck A, Stupp R, Prior JO. Performance of 18F-fluoro-ethyl-tyrosine (18F-FET) PET for the differential diagnosis of primary brain tumor: a systematic review and metaanalysis. J Nucl Med. 2012;53(2):207–14.CrossRefPubMed
11.
go back to reference Popperl G, Kreth FW, Mehrkens JH, Herms J, Seelos K, Koch W, et al. FET PET for the evaluation of untreated gliomas: correlation of FET uptake and uptake kinetics with tumour grading. Eur J Nucl Med Mol Imaging. 2007;34(12):1933–42.CrossRefPubMed Popperl G, Kreth FW, Mehrkens JH, Herms J, Seelos K, Koch W, et al. FET PET for the evaluation of untreated gliomas: correlation of FET uptake and uptake kinetics with tumour grading. Eur J Nucl Med Mol Imaging. 2007;34(12):1933–42.CrossRefPubMed
12.
go back to reference Jansen NL, Graute V, Armbruster L, Suchorska B, Lutz J, Eigenbrod S, et al. MRI-suspected low-grade glioma: is there a need to perform dynamic FET PET? Eur J Nucl Med Mol Imaging. 2012;39(6):1021–9.CrossRefPubMed Jansen NL, Graute V, Armbruster L, Suchorska B, Lutz J, Eigenbrod S, et al. MRI-suspected low-grade glioma: is there a need to perform dynamic FET PET? Eur J Nucl Med Mol Imaging. 2012;39(6):1021–9.CrossRefPubMed
13.
go back to reference Jansen NL, Suchorska B, Wenter V, Schmid-Tannwald C, Todica A, Eigenbrod S, et al. Prognostic significance of dynamic 18F-FET PET in newly diagnosed astrocytic high-grade glioma. J Nucl Med. 2015;56(1):9–15.CrossRefPubMed Jansen NL, Suchorska B, Wenter V, Schmid-Tannwald C, Todica A, Eigenbrod S, et al. Prognostic significance of dynamic 18F-FET PET in newly diagnosed astrocytic high-grade glioma. J Nucl Med. 2015;56(1):9–15.CrossRefPubMed
14.
go back to reference Pyka T, Gempt J, Ringel F, Huttinger S, van Marwick S, Nekolla S, et al. Prediction of glioma recurrence using dynamic (1)(8)F-fluoroethyltyrosine PET. AJNR Am J Neuroradiol. 2014;35(10):1924–9.CrossRefPubMed Pyka T, Gempt J, Ringel F, Huttinger S, van Marwick S, Nekolla S, et al. Prediction of glioma recurrence using dynamic (1)(8)F-fluoroethyltyrosine PET. AJNR Am J Neuroradiol. 2014;35(10):1924–9.CrossRefPubMed
15.
go back to reference Cheng NM, Fang YH, Chang JT, Huang CG, Tsan DL, Ng SH, et al. Textural features of pretreatment 18F-FDG PET/CT images: prognostic significance in patients with advanced T-stage oropharyngeal squamous cell carcinoma. J Nucl Med. 2013;54(10):1703–9.CrossRefPubMed Cheng NM, Fang YH, Chang JT, Huang CG, Tsan DL, Ng SH, et al. Textural features of pretreatment 18F-FDG PET/CT images: prognostic significance in patients with advanced T-stage oropharyngeal squamous cell carcinoma. J Nucl Med. 2013;54(10):1703–9.CrossRefPubMed
16.
go back to reference Tixier F, Le Rest CC, Hatt M, Albarghach N, Pradier O, Metges JP, et al. Intratumor heterogeneity characterized by textural features on baseline 18F-FDG PET images predicts response to concomitant radiochemotherapy in esophageal cancer. J Nucl Med. 2011;52(3):369–78.PubMedCentralCrossRefPubMed Tixier F, Le Rest CC, Hatt M, Albarghach N, Pradier O, Metges JP, et al. Intratumor heterogeneity characterized by textural features on baseline 18F-FDG PET images predicts response to concomitant radiochemotherapy in esophageal cancer. J Nucl Med. 2011;52(3):369–78.PubMedCentralCrossRefPubMed
17.
go back to reference Cook GJ, Yip C, Siddique M, Goh V, Chicklore S, Roy A, et al. Are pretreatment 18F-FDG PET tumor textural features in non-small cell lung cancer associated with response and survival after chemoradiotherapy? J Nucl Med. 2013;54(1):19–26.CrossRefPubMed Cook GJ, Yip C, Siddique M, Goh V, Chicklore S, Roy A, et al. Are pretreatment 18F-FDG PET tumor textural features in non-small cell lung cancer associated with response and survival after chemoradiotherapy? J Nucl Med. 2013;54(1):19–26.CrossRefPubMed
18.
go back to reference Tixier F, Hatt M, Valla C, Fleury V, Lamour C, Ezzouhri S, et al. Visual versus quantitative assessment of intratumor 18F-FDG PET uptake heterogeneity: prognostic value in non-small cell lung cancer. J Nucl Med. 2014;55(8):1235–41.CrossRefPubMed Tixier F, Hatt M, Valla C, Fleury V, Lamour C, Ezzouhri S, et al. Visual versus quantitative assessment of intratumor 18F-FDG PET uptake heterogeneity: prognostic value in non-small cell lung cancer. J Nucl Med. 2014;55(8):1235–41.CrossRefPubMed
19.
go back to reference Lutz K, Radbruch A, Wiestler B, Baumer P, Wick W, Bendszus M. Neuroradiological response criteria for high-grade gliomas. Clin Neuroradiol. 2011;21(4):199–205.CrossRefPubMed Lutz K, Radbruch A, Wiestler B, Baumer P, Wick W, Bendszus M. Neuroradiological response criteria for high-grade gliomas. Clin Neuroradiol. 2011;21(4):199–205.CrossRefPubMed
20.
go back to reference Popperl G, Kreth FW, Herms J, Koch W, Mehrkens JH, Gildehaus FJ, et al. Analysis of 18F-FET PET for grading of recurrent gliomas: is evaluation of uptake kinetics superior to standard methods? J Nucl Med. 2006;47(3):393–403.PubMed Popperl G, Kreth FW, Herms J, Koch W, Mehrkens JH, Gildehaus FJ, et al. Analysis of 18F-FET PET for grading of recurrent gliomas: is evaluation of uptake kinetics superior to standard methods? J Nucl Med. 2006;47(3):393–403.PubMed
21.
go back to reference Orlhac F, Soussan M, Maisonobe JA, Garcia CA, Vanderlinden B, Buvat I. Tumor texture analysis in 18F-FDG PET: relationships between texture parameters, histogram indices, standardized uptake values, metabolic volumes, and total lesion glycolysis. J Nucl Med. 2014;55(3):414–22.CrossRefPubMed Orlhac F, Soussan M, Maisonobe JA, Garcia CA, Vanderlinden B, Buvat I. Tumor texture analysis in 18F-FDG PET: relationships between texture parameters, histogram indices, standardized uptake values, metabolic volumes, and total lesion glycolysis. J Nucl Med. 2014;55(3):414–22.CrossRefPubMed
22.
go back to reference Amadasun M, King R. Textural features corresponding to textural properties. IEEE Trans Syst Man Cybern. 1989;19(5):1264–74.CrossRef Amadasun M, King R. Textural features corresponding to textural properties. IEEE Trans Syst Man Cybern. 1989;19(5):1264–74.CrossRef
23.
go back to reference Budczies J, Klauschen F, Sinn BV, Gyorffy B, Schmitt WD, Darb-Esfahani S, et al. Cutoff finder: a comprehensive and straightforward Web application enabling rapid biomarker cutoff optimization. PLoS One. 2012;7(12), e51862.PubMedCentralCrossRefPubMed Budczies J, Klauschen F, Sinn BV, Gyorffy B, Schmitt WD, Darb-Esfahani S, et al. Cutoff finder: a comprehensive and straightforward Web application enabling rapid biomarker cutoff optimization. PLoS One. 2012;7(12), e51862.PubMedCentralCrossRefPubMed
24.
go back to reference Bender R, Lange S. Adjusting for multiple testing—when and how? J Clin Epidemiol. 2001;54(4):343–9.CrossRefPubMed Bender R, Lange S. Adjusting for multiple testing—when and how? J Clin Epidemiol. 2001;54(4):343–9.CrossRefPubMed
25.
26.
go back to reference Ganeshan B, Goh V, Mandeville HC, Ng QS, Hoskin PJ, Miles KA. Non-small cell lung cancer: histopathologic correlates for texture parameters at CT. Radiology. 2013;266(1):326–36.CrossRefPubMed Ganeshan B, Goh V, Mandeville HC, Ng QS, Hoskin PJ, Miles KA. Non-small cell lung cancer: histopathologic correlates for texture parameters at CT. Radiology. 2013;266(1):326–36.CrossRefPubMed
27.
go back to reference Little SE, Popov S, Jury A, Bax DA, Doey L, Al-Sarraj S, et al. Receptor tyrosine kinase genes amplified in glioblastoma exhibit a mutual exclusivity in variable proportions reflective of individual tumor heterogeneity. Cancer Res. 2012;72(7):1614–20.CrossRefPubMed Little SE, Popov S, Jury A, Bax DA, Doey L, Al-Sarraj S, et al. Receptor tyrosine kinase genes amplified in glioblastoma exhibit a mutual exclusivity in variable proportions reflective of individual tumor heterogeneity. Cancer Res. 2012;72(7):1614–20.CrossRefPubMed
28.
go back to reference van Velden FH, Cheebsumon P, Yaqub M, Smit EF, Hoekstra OS, Lammertsma AA, et al. Evaluation of a cumulative SUV-volume histogram method for parameterizing heterogeneous intratumoural FDG uptake in non-small cell lung cancer PET studies. Eur J Nucl Med Mol Imaging. 2011;38(9):1636–47.PubMedCentralCrossRefPubMed van Velden FH, Cheebsumon P, Yaqub M, Smit EF, Hoekstra OS, Lammertsma AA, et al. Evaluation of a cumulative SUV-volume histogram method for parameterizing heterogeneous intratumoural FDG uptake in non-small cell lung cancer PET studies. Eur J Nucl Med Mol Imaging. 2011;38(9):1636–47.PubMedCentralCrossRefPubMed
29.
go back to reference Tixier F, Hatt M, Le Rest CC, Le Pogam A, Corcos L, Visvikis D. Reproducibility of tumor uptake heterogeneity characterization through textural feature analysis in 18F-FDG PET. J Nucl Med. 2012;53(5):693–700.PubMedCentralCrossRefPubMed Tixier F, Hatt M, Le Rest CC, Le Pogam A, Corcos L, Visvikis D. Reproducibility of tumor uptake heterogeneity characterization through textural feature analysis in 18F-FDG PET. J Nucl Med. 2012;53(5):693–700.PubMedCentralCrossRefPubMed
Metadata
Title
Textural analysis of pre-therapeutic [18F]-FET-PET and its correlation with tumor grade and patient survival in high-grade gliomas
Authors
Thomas Pyka
Jens Gempt
Daniela Hiob
Florian Ringel
Jürgen Schlegel
Stefanie Bette
Hans-Jürgen Wester
Bernhard Meyer
Stefan Förster
Publication date
01-01-2016
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 1/2016
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-015-3140-4

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