Combining imaging- and gene-based hypoxia biomarkers in cervical cancer improves prediction of chemoradiotherapy failure independent of intratumour heterogeneity.
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor
/ genetics
Chemoradiotherapy
/ adverse effects
Diagnostic Imaging
Female
Gene Expression Profiling
Humans
Middle Aged
Neoplasm Proteins
/ genetics
Norway
/ epidemiology
Prognosis
Progression-Free Survival
Treatment Outcome
Tumor Hypoxia
/ drug effects
Uterine Cervical Neoplasms
/ diagnostic imaging
Cervical cancer
Gene expression signature
Hypoxia
Intratumour heterogeneity
Medical imaging
Prognostic biomarker
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Jul 2020
Jul 2020
Historique:
received:
23
03
2020
revised:
18
05
2020
accepted:
02
06
2020
pubmed:
25
6
2020
medline:
26
5
2021
entrez:
25
6
2020
Statut:
ppublish
Résumé
Emerging biomarkers from medical imaging or molecular characterization of tumour biopsies open up for combining the two and exploiting their synergy in treatment planning of cancer patients. We generated a paired data set of imaging- and gene-based hypoxia biomarkers in cervical cancer, appraised the influence of intratumour heterogeneity in patient classification, and investigated the benefit of combining the methodologies in prediction of chemoradiotherapy failure. Hypoxic fraction from dynamic contrast enhanced (DCE)-MR images and an expression signature of six hypoxia-responsive genes were assessed as imaging- and gene-based biomarker, respectively in 118 patients. Dichotomous biomarker cutoff to yield similar hypoxia status by imaging and genes was defined in 41 patients, and the association was validated in the remaining 77 patients. The two biomarkers classified 75% of 118 patients with the same hypoxia status, and inconsistent classification was not related to imaging-defined intratumour heterogeneity in hypoxia. Gene-based hypoxia was independent on tumour cell fraction in the biopsies and showed minor heterogeneity across multiple samples in 9 tumours. Combining imaging- and gene-based classification gave a significantly better prediction of PFS than one biomarker alone. A combined dichotomous biomarker optimized in 77 patients showed a large separation in PFS between more and less hypoxic tumours, and separated the remaining 41 patients with different PFS. The combined biomarker showed prognostic value together with tumour stage in multivariate analysis. Combining imaging- and gene-based biomarkers may enable more precise and informative assessment of hypoxia-related chemoradiotherapy resistance in cervical cancer. Norwegian Cancer Society, South-Eastern Norway Regional Health Authority, and Norwegian Research Council.
Sections du résumé
BACKGROUND
BACKGROUND
Emerging biomarkers from medical imaging or molecular characterization of tumour biopsies open up for combining the two and exploiting their synergy in treatment planning of cancer patients. We generated a paired data set of imaging- and gene-based hypoxia biomarkers in cervical cancer, appraised the influence of intratumour heterogeneity in patient classification, and investigated the benefit of combining the methodologies in prediction of chemoradiotherapy failure.
METHODS
METHODS
Hypoxic fraction from dynamic contrast enhanced (DCE)-MR images and an expression signature of six hypoxia-responsive genes were assessed as imaging- and gene-based biomarker, respectively in 118 patients.
FINDINGS
RESULTS
Dichotomous biomarker cutoff to yield similar hypoxia status by imaging and genes was defined in 41 patients, and the association was validated in the remaining 77 patients. The two biomarkers classified 75% of 118 patients with the same hypoxia status, and inconsistent classification was not related to imaging-defined intratumour heterogeneity in hypoxia. Gene-based hypoxia was independent on tumour cell fraction in the biopsies and showed minor heterogeneity across multiple samples in 9 tumours. Combining imaging- and gene-based classification gave a significantly better prediction of PFS than one biomarker alone. A combined dichotomous biomarker optimized in 77 patients showed a large separation in PFS between more and less hypoxic tumours, and separated the remaining 41 patients with different PFS. The combined biomarker showed prognostic value together with tumour stage in multivariate analysis.
INTERPRETATION
CONCLUSIONS
Combining imaging- and gene-based biomarkers may enable more precise and informative assessment of hypoxia-related chemoradiotherapy resistance in cervical cancer.
FUNDING
BACKGROUND
Norwegian Cancer Society, South-Eastern Norway Regional Health Authority, and Norwegian Research Council.
Identifiants
pubmed: 32580139
pii: S2352-3964(20)30216-4
doi: 10.1016/j.ebiom.2020.102841
pmc: PMC7317686
pii:
doi:
Substances chimiques
Biomarkers, Tumor
0
Neoplasm Proteins
0
Types de publication
Clinical Trial
Journal Article
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
102841Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest HL is registered as inventor of a patent application covering the clinical use of the hypoxia gene signature (WO2013/124,738).
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