Repeat FMISO-PET imaging weakly correlates with hypoxia-associated gene expressions for locally advanced HNSCC treated by primary radiochemotherapy.


Journal

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
ISSN: 1879-0887
Titre abrégé: Radiother Oncol
Pays: Ireland
ID NLM: 8407192

Informations de publication

Date de publication:
06 2019
Historique:
received: 26 11 2018
revised: 07 02 2019
accepted: 25 02 2019
pubmed: 25 4 2019
medline: 4 3 2020
entrez: 25 4 2019
Statut: ppublish

Résumé

Hypoxia is an important factor of tumour resistance to radiotherapy, chemotherapy and potentially immunotherapy. It can be measured e.g. by positron emission tomography (PET) imaging or hypoxia-associated gene expressions from tumour biopsies. Here we correlate [ FMISO-PET/CT images of 50 HNSCC patients were acquired at four time-points before and during RCTx. For 42 of these patients, hypoxia-associated gene expressions were evaluated by nanoString technology based on a biopsy obtained before any treatment. The FMISO-PET parameters tumour-to-background ratio and hypoxic volume were correlated to the expressions of 58 hypoxia-associated genes using the Spearman correlation coefficient ρ. Three hypoxia-associated gene signatures were compared regarding their correlation with the FMISO-PET parameters using their median expression. In addition, the correlation with tumour volume was analysed. The impact of both hypoxia measurement methods on loco-regional tumour control (LRC) and overall survival (OS) was assessed by Cox regression. The median expression of hypoxia-associated genes was weakly correlated to hypoxia measured by FMISO-PET imaging (ρ ≤ 0.43), with higher correlations to imaging after weeks 1 and 2 of treatment (p < 0.001). Moderate correlations were obtained between FMISO-PET imaging and tumour volume (ρ ≤ 0.69). Prognostic models for LRC and OS based on the FMISO-PET parameters could not be improved by including hypoxia classifiers. We observed low correlations between hypoxia FMISO-PET parameters and expressions of hypoxia-associated genes. Since FMISO-PET showed a superior patient stratification, it may be the preferred biomarker over hypoxia-associated genes for stratifying patients with locally advanced HNSCC treated by primary RCTx.

Sections du résumé

BACKGROUND
Hypoxia is an important factor of tumour resistance to radiotherapy, chemotherapy and potentially immunotherapy. It can be measured e.g. by positron emission tomography (PET) imaging or hypoxia-associated gene expressions from tumour biopsies. Here we correlate [
METHODS
FMISO-PET/CT images of 50 HNSCC patients were acquired at four time-points before and during RCTx. For 42 of these patients, hypoxia-associated gene expressions were evaluated by nanoString technology based on a biopsy obtained before any treatment. The FMISO-PET parameters tumour-to-background ratio and hypoxic volume were correlated to the expressions of 58 hypoxia-associated genes using the Spearman correlation coefficient ρ. Three hypoxia-associated gene signatures were compared regarding their correlation with the FMISO-PET parameters using their median expression. In addition, the correlation with tumour volume was analysed. The impact of both hypoxia measurement methods on loco-regional tumour control (LRC) and overall survival (OS) was assessed by Cox regression.
RESULTS
The median expression of hypoxia-associated genes was weakly correlated to hypoxia measured by FMISO-PET imaging (ρ ≤ 0.43), with higher correlations to imaging after weeks 1 and 2 of treatment (p < 0.001). Moderate correlations were obtained between FMISO-PET imaging and tumour volume (ρ ≤ 0.69). Prognostic models for LRC and OS based on the FMISO-PET parameters could not be improved by including hypoxia classifiers.
CONCLUSION
We observed low correlations between hypoxia FMISO-PET parameters and expressions of hypoxia-associated genes. Since FMISO-PET showed a superior patient stratification, it may be the preferred biomarker over hypoxia-associated genes for stratifying patients with locally advanced HNSCC treated by primary RCTx.

Identifiants

pubmed: 31015169
pii: S0167-8140(19)30102-1
doi: 10.1016/j.radonc.2019.02.020
pii:
doi:

Substances chimiques

Fluorine Radioisotopes 0
Radiopharmaceuticals 0
fluoromisonidazole 082285VIDF
Misonidazole 8FE7LTN8XE

Types de publication

Journal Article Observational Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

43-50

Informations de copyright

Copyright © 2019 Elsevier B.V. All rights reserved.

Auteurs

Steffen Löck (S)

OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Germany; Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; German Cancer Consortium (DKTK), Partner Site Dresden, Germany; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany. Electronic address: steffen.loeck@oncoray.de.

Annett Linge (A)

OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Germany; Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; German Cancer Consortium (DKTK), Partner Site Dresden, Germany; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.

Annekatrin Seidlitz (A)

OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Germany; Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.

Anna Bandurska-Luque (A)

OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Germany; Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.

Alexander Nowak (A)

National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany, and; Helmholtz Association/Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany; Department of Oral and Maxillofacial Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.

Volker Gudziol (V)

National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany, and; Helmholtz Association/Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany; Department of Otorhinolaryngology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.

Frank Buchholz (F)

National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany, and; Helmholtz Association/Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany; University Cancer Center (UCC), Medical Systems Biology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.

Daniela E Aust (DE)

National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany, and; Helmholtz Association/Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany; Institute of Pathology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; Tumour- and Normal Tissue Bank, University Cancer Center (UCC), University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.

Gustavo B Baretton (GB)

National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany, and; Helmholtz Association/Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany; Institute of Pathology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; Tumour- and Normal Tissue Bank, University Cancer Center (UCC), University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.

Klaus Zöphel (K)

National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany, and; Helmholtz Association/Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany; Department of Nuclear Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.

Jörg Steinbach (J)

National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany, and; Helmholtz Association/Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany; Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Germany.

Jörg Kotzerke (J)

National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany, and; Helmholtz Association/Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany; Department of Nuclear Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.

Jens Overgaard (J)

Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark.

Daniel Zips (D)

Department of Radiation Oncology, Eberhard Karls Universität Tübingen, Germany; German Cancer Consortium (DKTK), Partner Site Tübingen, Germany.

Mechthild Krause (M)

OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Germany; Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; German Cancer Consortium (DKTK), Partner Site Dresden, Germany; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany; National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany, and; Helmholtz Association/Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany; Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology - OncoRay, Germany.

Michael Baumann (M)

OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Germany; Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; German Cancer Consortium (DKTK), Partner Site Dresden, Germany; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany; National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany, and; Helmholtz Association/Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany; Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology - OncoRay, Germany.

Esther G C Troost (EGC)

OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Germany; Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; German Cancer Consortium (DKTK), Partner Site Dresden, Germany; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany; National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany, and; Helmholtz Association/Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany; Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology - OncoRay, Germany.

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