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The impact of tumor metabolic activity assessed by (18)F-FET amino acid PET imaging in particle radiotherapy of high-grade glioma patients

BACKGROUND: Selective uptake of (18)F-fluoro-ethyl-tyrosine ((18)F-FET) is used in high-grade glioma (HGG) to assess tumor metabolic activity via positron emission tomography (PET). We aim to investigate its value for target volume definition, as a prognosticator, and associations with whole-blood t...

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Autores principales: Waltenberger, Maria, Furkel, Jennifer, Röhrich, Manuel, Salome, Patrick, Debus, Charlotte, Tawk, Bouchra, Gahlawat, Aoife Ward, Kudak, Andreas, Dostal, Matthias, Wirkner, Ute, Schwager, Christian, Herold-Mende, Christel, Combs, Stephanie E., König, Laila, Debus, Jürgen, Haberkorn, Uwe, Abdollahi, Amir, Knoll, Maximilian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9531169/
https://www.ncbi.nlm.nih.gov/pubmed/36203443
http://dx.doi.org/10.3389/fonc.2022.901390
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author Waltenberger, Maria
Furkel, Jennifer
Röhrich, Manuel
Salome, Patrick
Debus, Charlotte
Tawk, Bouchra
Gahlawat, Aoife Ward
Kudak, Andreas
Dostal, Matthias
Wirkner, Ute
Schwager, Christian
Herold-Mende, Christel
Combs, Stephanie E.
König, Laila
Debus, Jürgen
Haberkorn, Uwe
Abdollahi, Amir
Knoll, Maximilian
author_facet Waltenberger, Maria
Furkel, Jennifer
Röhrich, Manuel
Salome, Patrick
Debus, Charlotte
Tawk, Bouchra
Gahlawat, Aoife Ward
Kudak, Andreas
Dostal, Matthias
Wirkner, Ute
Schwager, Christian
Herold-Mende, Christel
Combs, Stephanie E.
König, Laila
Debus, Jürgen
Haberkorn, Uwe
Abdollahi, Amir
Knoll, Maximilian
author_sort Waltenberger, Maria
collection PubMed
description BACKGROUND: Selective uptake of (18)F-fluoro-ethyl-tyrosine ((18)F-FET) is used in high-grade glioma (HGG) to assess tumor metabolic activity via positron emission tomography (PET). We aim to investigate its value for target volume definition, as a prognosticator, and associations with whole-blood transcriptome liquid biopsy (WBT lbx) for which we recently reported feasibility to mirror tumor characteristics and response to particle irradiation in recurrent HGG (rHGG). METHODS: (18)F-FET-PET data from n = 43 patients with primary glioblastoma (pGBM) and n = 33 patients with rHGG were assessed. pGBM patients were irradiated with photons and sequential proton/carbon boost, and rHGG patients were treated with carbon re-irradiation (CIR). WBT (Illumina HumanHT-12 Expression BeadChips) lbx was available for n = 9 patients from the rHGG cohort. PET isocontours (40%–70% SUVmax, 10% steps) and MRI-based treatment volumes (MRIvol) were compared using the conformity index (CI) (pGBM, n = 16; rHGG, n = 27). Associations with WBT lbx data were tested on gene expression level and inferred pathways activity scores (PROGENy) and from transcriptome estimated cell fractions (CIBERSORT, xCell). RESULTS: In pGBM, median SUVmax was higher in PET acquired pre-radiotherapy (4.1, range (R) 1.5–7.8; n = 20) vs. during radiotherapy (3.3, R 1.5–5.7, n = 23; p = 0.03) and in non-resected (4.7, R 2.9–7.9; n = 11) vs. resected tumors (3.3, R 1.5–7.8, n = 32; p = 0.01). In rHGG, a trend toward higher SUVmax values in grade IV tumors was observed (p = 0.13). Median MRIvol was 32.34 (R 8.75–108.77) cm(3) in pGBM (n = 16) and 20.77 (R 0.63–128.44) cm(3) in rHGG patients (n = 27). The highest median CI was observed for 40% (pGBM, 0.31) and 50% (rHGG, 0.43, all tumors) isodose, with 70% (40%) isodose in grade III (IV) rHGG tumors (median CI, 0.38 and 0.49). High SUVmax was linked to shorter survival in pGBM (>3.3, p = 0.001, OR 6.0 [2.1–17.4]) and rHGG (>2.8, p = 0.02, OR 4.1 [1.2–13.9]). SUVmax showed associations with inferred monocyte fractions, hypoxia, and TGFbeta pathway activity and links to immune checkpoint gene expression from WBT lbx. CONCLUSION: The benefits of (18)F-FET-PET imaging on gross tumor volume (GTV) definition for particle radiotherapy warrant further evaluation. SUVmax might assist in prognostic stratification of HGG patients for particle radiotherapy, highlights heterogeneity in rHGG, and is positively associated with unfavorable signatures in peripheral whole-blood transcriptomes.
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spelling pubmed-95311692022-10-05 The impact of tumor metabolic activity assessed by (18)F-FET amino acid PET imaging in particle radiotherapy of high-grade glioma patients Waltenberger, Maria Furkel, Jennifer Röhrich, Manuel Salome, Patrick Debus, Charlotte Tawk, Bouchra Gahlawat, Aoife Ward Kudak, Andreas Dostal, Matthias Wirkner, Ute Schwager, Christian Herold-Mende, Christel Combs, Stephanie E. König, Laila Debus, Jürgen Haberkorn, Uwe Abdollahi, Amir Knoll, Maximilian Front Oncol Oncology BACKGROUND: Selective uptake of (18)F-fluoro-ethyl-tyrosine ((18)F-FET) is used in high-grade glioma (HGG) to assess tumor metabolic activity via positron emission tomography (PET). We aim to investigate its value for target volume definition, as a prognosticator, and associations with whole-blood transcriptome liquid biopsy (WBT lbx) for which we recently reported feasibility to mirror tumor characteristics and response to particle irradiation in recurrent HGG (rHGG). METHODS: (18)F-FET-PET data from n = 43 patients with primary glioblastoma (pGBM) and n = 33 patients with rHGG were assessed. pGBM patients were irradiated with photons and sequential proton/carbon boost, and rHGG patients were treated with carbon re-irradiation (CIR). WBT (Illumina HumanHT-12 Expression BeadChips) lbx was available for n = 9 patients from the rHGG cohort. PET isocontours (40%–70% SUVmax, 10% steps) and MRI-based treatment volumes (MRIvol) were compared using the conformity index (CI) (pGBM, n = 16; rHGG, n = 27). Associations with WBT lbx data were tested on gene expression level and inferred pathways activity scores (PROGENy) and from transcriptome estimated cell fractions (CIBERSORT, xCell). RESULTS: In pGBM, median SUVmax was higher in PET acquired pre-radiotherapy (4.1, range (R) 1.5–7.8; n = 20) vs. during radiotherapy (3.3, R 1.5–5.7, n = 23; p = 0.03) and in non-resected (4.7, R 2.9–7.9; n = 11) vs. resected tumors (3.3, R 1.5–7.8, n = 32; p = 0.01). In rHGG, a trend toward higher SUVmax values in grade IV tumors was observed (p = 0.13). Median MRIvol was 32.34 (R 8.75–108.77) cm(3) in pGBM (n = 16) and 20.77 (R 0.63–128.44) cm(3) in rHGG patients (n = 27). The highest median CI was observed for 40% (pGBM, 0.31) and 50% (rHGG, 0.43, all tumors) isodose, with 70% (40%) isodose in grade III (IV) rHGG tumors (median CI, 0.38 and 0.49). High SUVmax was linked to shorter survival in pGBM (>3.3, p = 0.001, OR 6.0 [2.1–17.4]) and rHGG (>2.8, p = 0.02, OR 4.1 [1.2–13.9]). SUVmax showed associations with inferred monocyte fractions, hypoxia, and TGFbeta pathway activity and links to immune checkpoint gene expression from WBT lbx. CONCLUSION: The benefits of (18)F-FET-PET imaging on gross tumor volume (GTV) definition for particle radiotherapy warrant further evaluation. SUVmax might assist in prognostic stratification of HGG patients for particle radiotherapy, highlights heterogeneity in rHGG, and is positively associated with unfavorable signatures in peripheral whole-blood transcriptomes. Frontiers Media S.A. 2022-09-20 /pmc/articles/PMC9531169/ /pubmed/36203443 http://dx.doi.org/10.3389/fonc.2022.901390 Text en Copyright © 2022 Waltenberger, Furkel, Röhrich, Salome, Debus, Tawk, Gahlawat, Kudak, Dostal, Wirkner, Schwager, Herold-Mende, Combs, König, Debus, Haberkorn, Abdollahi and Knoll https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Waltenberger, Maria
Furkel, Jennifer
Röhrich, Manuel
Salome, Patrick
Debus, Charlotte
Tawk, Bouchra
Gahlawat, Aoife Ward
Kudak, Andreas
Dostal, Matthias
Wirkner, Ute
Schwager, Christian
Herold-Mende, Christel
Combs, Stephanie E.
König, Laila
Debus, Jürgen
Haberkorn, Uwe
Abdollahi, Amir
Knoll, Maximilian
The impact of tumor metabolic activity assessed by (18)F-FET amino acid PET imaging in particle radiotherapy of high-grade glioma patients
title The impact of tumor metabolic activity assessed by (18)F-FET amino acid PET imaging in particle radiotherapy of high-grade glioma patients
title_full The impact of tumor metabolic activity assessed by (18)F-FET amino acid PET imaging in particle radiotherapy of high-grade glioma patients
title_fullStr The impact of tumor metabolic activity assessed by (18)F-FET amino acid PET imaging in particle radiotherapy of high-grade glioma patients
title_full_unstemmed The impact of tumor metabolic activity assessed by (18)F-FET amino acid PET imaging in particle radiotherapy of high-grade glioma patients
title_short The impact of tumor metabolic activity assessed by (18)F-FET amino acid PET imaging in particle radiotherapy of high-grade glioma patients
title_sort impact of tumor metabolic activity assessed by (18)f-fet amino acid pet imaging in particle radiotherapy of high-grade glioma patients
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9531169/
https://www.ncbi.nlm.nih.gov/pubmed/36203443
http://dx.doi.org/10.3389/fonc.2022.901390
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