Generation of biological hypotheses by functional imaging links tumor hypoxia to radiation induced tissue inflammation/glucose uptake in head and neck cancer.


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:
02 2021
Historique:
received: 17 07 2020
revised: 09 10 2020
accepted: 21 10 2020
pubmed: 1 12 2020
medline: 24 4 2021
entrez: 30 11 2020
Statut: ppublish

Résumé

Positron emission tomography (PET) is a functional imaging modality which is able to deliver tracer specific biological information, e.g. about glucose uptake, inflammation or hypoxia of tumors. We performed a proof-of-principle study that used different tracers and expanded the analytical scope to non-tumor structures to evaluate tumor-host interactions. Based on a previously reported prospective imaging study on 50 patients treated with curative intent chemoradiation (CRT) for head and neck squamous cell carcinoma, PET-based hypoxia and normal tissue inflammation measured by repeat 18F-fluoromisonidazole (FMISO) PET and 18F-fluorodesoxyglucose (FDG) PET, respectively, were correlated using the Spearman correlation coefficient R. PET parameters determined before and during CRT (week 1, 2 and 5), were associated with local tumor control and overall survival. Tumor hypoxia at all measured times showed an inverse correlation with mid-treatment FDG-uptake of non-tumor affected oral (sub-)mucosa with R values between -0.35 and -0.6 (all p < 0.05). Mucosal FDG-uptake and mucosal hypoxia correlated positively but weaker (R values between 0.2 and 0.45). More tumor hypoxia in FMISO-PET (week 2) and less FDG-uptake of (sub-)mucosa in FDG-PET (week 4) were significantly associated with worse LC (FMISO TBR We report first clinical evidence that tumor hypoxia is inversely correlated with increased FDG-uptake during radiation, potentially expressing inflammation. This observation merits further research and may have important implication for future research on tumor hypoxia and radio-immunology. Our study demonstrates that functional imaging can be utilized to assess complex tumor-host interactions and generate novel biological insights in vivo vero.

Sections du résumé

BACKGROUND AND PURPOSE
Positron emission tomography (PET) is a functional imaging modality which is able to deliver tracer specific biological information, e.g. about glucose uptake, inflammation or hypoxia of tumors. We performed a proof-of-principle study that used different tracers and expanded the analytical scope to non-tumor structures to evaluate tumor-host interactions.
MATERIALS AND METHODS
Based on a previously reported prospective imaging study on 50 patients treated with curative intent chemoradiation (CRT) for head and neck squamous cell carcinoma, PET-based hypoxia and normal tissue inflammation measured by repeat 18F-fluoromisonidazole (FMISO) PET and 18F-fluorodesoxyglucose (FDG) PET, respectively, were correlated using the Spearman correlation coefficient R. PET parameters determined before and during CRT (week 1, 2 and 5), were associated with local tumor control and overall survival.
RESULTS
Tumor hypoxia at all measured times showed an inverse correlation with mid-treatment FDG-uptake of non-tumor affected oral (sub-)mucosa with R values between -0.35 and -0.6 (all p < 0.05). Mucosal FDG-uptake and mucosal hypoxia correlated positively but weaker (R values between 0.2 and 0.45). More tumor hypoxia in FMISO-PET (week 2) and less FDG-uptake of (sub-)mucosa in FDG-PET (week 4) were significantly associated with worse LC (FMISO TBR
CONCLUSION
We report first clinical evidence that tumor hypoxia is inversely correlated with increased FDG-uptake during radiation, potentially expressing inflammation. This observation merits further research and may have important implication for future research on tumor hypoxia and radio-immunology. Our study demonstrates that functional imaging can be utilized to assess complex tumor-host interactions and generate novel biological insights in vivo vero.

Identifiants

pubmed: 33252044
pii: S0167-8140(20)30877-X
doi: 10.1016/j.radonc.2020.10.030
pii:
doi:

Substances chimiques

Radiopharmaceuticals 0
Fluorodeoxyglucose F18 0Z5B2CJX4D
Misonidazole 8FE7LTN8XE
Glucose IY9XDZ35W2

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

204-211

Informations de copyright

Copyright © 2020 Elsevier B.V. All rights reserved.

Auteurs

Sebastian Zschaeck (S)

Department of Radiotherapy and Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; German Cancer Consortium (DKTK), Dresden, Germany, and German Cancer Research Center (DKFZ) Heidelberg, Germany; OncoRay, National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden, Rossendorf, Germany; Charité Universitätsmedizin Berlin, Department of Radiation Oncology, Berlin, Germany; Berlin Institute of Health (BIH), Berlin, Germany. Electronic address: Sebastian.Zschaeck@charite.de.

Klaus Zöphel (K)

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

Annekatrin Seidlitz (A)

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

Daniel Zips (D)

Department of Radiotherapy and Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; German Cancer Consortium (DKTK), Tübingen, Germany, and German Cancer Research Center (DKFZ) Heidelberg, Germany; Department of Radiation Oncology, University Hospital and Medical Faculty, Eberhard Karls University Tübingen, Germany.

Jörg Kotzerke (J)

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

Michael Baumann (M)

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

Esther G C Troost (EGC)

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

Steffen Löck (S)

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

Mechthild Krause (M)

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

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Classifications MeSH