Non-invasive imaging prediction of tumor hypoxia: A novel developed and externally validated CT and FDG-PET-based radiomic signatures.


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:
12 2020
Historique:
received: 02 07 2019
revised: 09 10 2020
accepted: 12 10 2020
pubmed: 3 11 2020
medline: 15 4 2021
entrez: 2 11 2020
Statut: ppublish

Résumé

Tumor hypoxia increases resistance to radiotherapy and systemic therapy. Our aim was to develop and validate a disease-agnostic and disease-specific CT (+FDG-PET) based radiomics hypoxia classification signature. A total of 808 patients with imaging data were included: N = 100 training/N = 183 external validation cases for a disease-agnostic CT hypoxia classification signature, N = 76 training/N = 39 validation cases for the H&N CT signature and N = 62 training/N = 36 validation cases for the Lung CT signature. The primary gross tumor volumes (GTV) were manually defined by experts on CT. In order to dichotomize between hypoxic/well-oxygenated tumors a threshold of 20% was used for the [ A 11 feature "disease-agnostic CT model" reached AUC's of respectively 0.78 (95% confidence interval [CI], 0.62-0.94), 0.82 (95% CI, 0.67-0.96) and 0.78 (95% CI, 0.67-0.89) in three external validation datasets. A "disease-agnostic FDG-PET model" reached an AUC of 0.73 (0.95% CI, 0.49-0.97) in validation by combining 5 features. The highest "lung-specific CT model" reached an AUC of 0.80 (0.95% CI, 0.65-0.95) in validation with 4 CT features, while the "H&N-specific CT model" reached an AUC of 0.84 (0.95% CI, 0.64-1.00) in validation with 15 CT features. A tumor volume-alone model was unable to significantly classify patients as hypoxia-positive/ negative. A significant survival split (P = 0.037) was found between CT-classified hypoxia strata in an external H&N cohort (n = 517), while 117 significant hypoxia gene-CT signature feature associations were found in an external lung cohort (n = 80). The disease-specific radiomics signatures perform better than the disease agnostic ones. By identifying hypoxic patients our signatures have the potential to enrich interventional hypoxia-targeting trials.

Sections du résumé

BACKGROUND
Tumor hypoxia increases resistance to radiotherapy and systemic therapy. Our aim was to develop and validate a disease-agnostic and disease-specific CT (+FDG-PET) based radiomics hypoxia classification signature.
MATERIAL AND METHODS
A total of 808 patients with imaging data were included: N = 100 training/N = 183 external validation cases for a disease-agnostic CT hypoxia classification signature, N = 76 training/N = 39 validation cases for the H&N CT signature and N = 62 training/N = 36 validation cases for the Lung CT signature. The primary gross tumor volumes (GTV) were manually defined by experts on CT. In order to dichotomize between hypoxic/well-oxygenated tumors a threshold of 20% was used for the [
RESULTS
A 11 feature "disease-agnostic CT model" reached AUC's of respectively 0.78 (95% confidence interval [CI], 0.62-0.94), 0.82 (95% CI, 0.67-0.96) and 0.78 (95% CI, 0.67-0.89) in three external validation datasets. A "disease-agnostic FDG-PET model" reached an AUC of 0.73 (0.95% CI, 0.49-0.97) in validation by combining 5 features. The highest "lung-specific CT model" reached an AUC of 0.80 (0.95% CI, 0.65-0.95) in validation with 4 CT features, while the "H&N-specific CT model" reached an AUC of 0.84 (0.95% CI, 0.64-1.00) in validation with 15 CT features. A tumor volume-alone model was unable to significantly classify patients as hypoxia-positive/ negative. A significant survival split (P = 0.037) was found between CT-classified hypoxia strata in an external H&N cohort (n = 517), while 117 significant hypoxia gene-CT signature feature associations were found in an external lung cohort (n = 80).
CONCLUSION
The disease-specific radiomics signatures perform better than the disease agnostic ones. By identifying hypoxic patients our signatures have the potential to enrich interventional hypoxia-targeting trials.

Identifiants

pubmed: 33137396
pii: S0167-8140(20)30852-5
doi: 10.1016/j.radonc.2020.10.016
pii:
doi:

Substances chimiques

Fluorodeoxyglucose F18 0Z5B2CJX4D

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

97-105

Informations de copyright

Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.

Auteurs

Sebastian Sanduleanu (S)

The-D-Lab, Dpt of Precision Medicine, GROW - School for Oncology, Maastricht University Medical Centre+, The Netherlands. Electronic address: s.sanduleanu@maastrichtuniversity.nl.

Arthur Jochems (A)

The-D-Lab, Dpt of Precision Medicine, GROW - School for Oncology, Maastricht University Medical Centre+, The Netherlands.

Taman Upadhaya (T)

Laboratory of Medical Information Processing (LaTIM), INSERM, UMR 1101, Univ Brest, France; Department of Radiation Oncology, University of California, 1600 Divisadero Street, CA 94115, San Francisco, United States.

Aniek J G Even (AJG)

The-D-Lab, Dpt of Precision Medicine, GROW - School for Oncology, Maastricht University Medical Centre+, The Netherlands.

Ralph T H Leijenaar (RTH)

The-D-Lab, Dpt of Precision Medicine, GROW - School for Oncology, Maastricht University Medical Centre+, The Netherlands.

Frank J W M Dankers (FJWM)

Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, The Netherlands.

Remy Klaassen (R)

Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Henry C Woodruff (HC)

The-D-Lab, Dpt of Precision Medicine, GROW - School for Oncology, Maastricht University Medical Centre+, The Netherlands; Department of Radiology and Nuclear Imaging, GROW - school for Oncology, Maastricht University Medical Centre+, The Netherlands.

Mathieu Hatt (M)

Laboratory of Medical Information Processing (LaTIM), INSERM, UMR 1101, Univ Brest, France.

Hans J A M Kaanders (HJAM)

Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, The Netherlands.

Olga Hamming-Vrieze (O)

Department of Radiation Oncology, Antoni van Leeuwenhoek - Netherlands Cancer institute, Amsterdam, The Netherlands.

Hanneke W M van Laarhoven (HWM)

Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Rathan M Subramiam (RM)

Boston University School of Medicine, United States; Division of Nuclear Medicine, Russell H Morgan Department of Radiology and Radiologic Sciences, Johns Hopkins Medical Institutions, Baltimore, United States.

Shao Hui Huang (SH)

Department of Radiation Oncology, Princess Margaret Cancer Center, University of Toronto, Canada.

Brian O'Sullivan (B)

Department of Radiation Oncology, Princess Margaret Cancer Center, University of Toronto, Canada.

Scott V Bratman (SV)

Department of Radiation Oncology, Princess Margaret Cancer Center, University of Toronto, Canada.

Ludwig J Dubois (LJ)

Department of Precision Medicine, The M-LAB, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre+, The Netherlands.

Razvan L Miclea (RL)

Department of Radiology and Nuclear Imaging, GROW - school for Oncology, Maastricht University Medical Centre+, The Netherlands.

Dario Di Perri (D)

Center of Molecular Imaging, Radiotherapy and Oncology (MIRO), Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain, Belgium; Department of Radiation Oncology, Cliniques universitaires Saint-Luc, Brussels, Belgium.

Xavier Geets (X)

Center of Molecular Imaging, Radiotherapy and Oncology (MIRO), Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain, Belgium; Department of Radiation Oncology, Cliniques universitaires Saint-Luc, Brussels, Belgium.

Mireia Crispin-Ortuzar (M)

Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, United States; Cancer Research UK Cambridge Institute, University of Cambridge, UK.

Aditya Apte (A)

Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, United States.

Joseph O Deasy (JO)

Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, United States.

Jung Hun Oh (JH)

Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, United States.

Nancy Y Lee (NY)

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, United States.

John L Humm (JL)

Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, United States.

Heiko Schöder (H)

Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, United States.

Dirk De Ruysscher (D)

Department of Radiation Oncology (Maastro), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre+, The Netherlands.

Frank Hoebers (F)

Department of Radiation Oncology (Maastro), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre+, The Netherlands.

Philippe Lambin (P)

The-D-Lab, Dpt of Precision Medicine, GROW - School for Oncology, Maastricht University Medical Centre+, The Netherlands; Department of Radiology and Nuclear Imaging, GROW - school for Oncology, Maastricht University Medical Centre+, The Netherlands.

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