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dc.contributor.authorSalem, A
dc.contributor.authorLittle, RA
dc.contributor.authorLatif, A
dc.contributor.authorFeatherstone, AK
dc.contributor.authorBabur, M
dc.contributor.authorPeset, I
dc.contributor.authorCheung, S
dc.contributor.authorWatson, Y
dc.contributor.authorTessyman, V
dc.contributor.authorMistry, H
dc.contributor.authorAshton, G
dc.contributor.authorBehan, C
dc.contributor.authorMatthews, JC
dc.contributor.authorAsselin, M-C
dc.contributor.authorBristow, RG
dc.contributor.authorJackson, A
dc.contributor.authorParker, GJM
dc.contributor.authorFaivre-Finn, C
dc.contributor.authorWilliams, KJ
dc.contributor.authorO'Connor, JPB
dc.date.accessioned2020-08-13T13:13:30Z
dc.date.issued2019-07
dc.identifier.citationClinical cancer research : an official journal of the American Association for Cancer Research, 2019, 25 (13), pp. 3818 - 3829
dc.identifier.issn1078-0432
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3959
dc.identifier.eissn1557-3265
dc.identifier.doi10.1158/1078-0432.ccr-18-3932
dc.description.abstractPurpose Hypoxia is associated with poor prognosis and is predictive of poor response to cancer treatments, including radiotherapy. Developing noninvasive biomarkers that both detect hypoxia prior to treatment and track change in tumor hypoxia following treatment is required urgently.Experimental design We evaluated the ability of oxygen-enhanced MRI (OE-MRI) to map and quantify therapy-induced changes in tumor hypoxia by measuring oxygen-refractory signals in perfused tissue (perfused Oxy-R). Clinical first-in-human study in patients with non-small cell lung cancer (NSCLC) was performed alongside preclinical experiments in two xenograft tumors (Calu6 NSCLC model and U87 glioma model).Results MRI perfused Oxy-R tumor fraction measurement of hypoxia was validated with ex vivo tissue pathology in both xenograft models. Calu6 and U87 experiments showed that MRI perfused Oxy-R tumor volume was reduced relative to control following single fraction 10-Gy radiation and fractionated chemoradiotherapy ( P < 0.001) due to both improved perfusion and reduced oxygen consumption rate. Next, evaluation of 23 patients with NSCLC showed that OE-MRI was clinically feasible and that tumor perfused Oxy-R volume is repeatable [interclass correlation coefficient: 0.961 (95% CI, 0.858-0.990); coefficient of variation: 25.880%]. Group-wise perfused Oxy-R volume was reduced at 14 days following start of radiotherapy ( P = 0.015). OE-MRI detected between-subject variation in hypoxia modification in both xenograft and patient tumors.Conclusions These findings support applying OE-MRI biomarkers to monitor hypoxia modification, to stratify patients in clinical trials of hypoxia-modifying therapies, to identify patients with hypoxic tumors that may fail treatment with immunotherapy, and to guide adaptive radiotherapy by mapping regional hypoxia.
dc.formatPrint-Electronic
dc.format.extent3818 - 3829
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectCell Line, Tumor
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectCarcinoma, Non-Small-Cell Lung
dc.subjectLung Neoplasms
dc.subjectDisease Models, Animal
dc.subjectOxygen
dc.subjectMagnetic Resonance Imaging
dc.subjectImage Enhancement
dc.subjectTumor Burden
dc.subjectReproducibility of Results
dc.subjectXenograft Model Antitumor Assays
dc.subjectRegional Blood Flow
dc.subjectBiomarkers
dc.subjectPrecision Medicine
dc.subjectHypoxia
dc.titleOxygen-enhanced MRI Is Feasible, Repeatable, and Detects Radiotherapy-induced Change in Hypoxia in Xenograft Models and in Patients with Non-small Cell Lung Cancer.
dc.typeJournal Article
dcterms.dateAccepted2019-03-14
rioxxterms.versionofrecord10.1158/1078-0432.ccr-18-3932
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2019-07
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfClinical cancer research : an official journal of the American Association for Cancer Research
pubs.issue13
pubs.notesNo embargo
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Quantitative Biomedical Imaging
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Quantitative Biomedical Imaging
pubs.publication-statusPublished
pubs.volume25
pubs.embargo.termsNo embargo
icr.researchteamQuantitative Biomedical Imagingen_US
dc.contributor.icrauthorO'Connor, James Patricken


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