Show simple item record

dc.contributor.authorWalker, AK
dc.contributor.authorKaraszi, K
dc.contributor.authorValentine, H
dc.contributor.authorStrauss, VY
dc.contributor.authorChoudhury, A
dc.contributor.authorMcGill, S
dc.contributor.authorWen, K
dc.contributor.authorBrown, MD
dc.contributor.authorRamani, V
dc.contributor.authorBhattarai, S
dc.contributor.authorTeo, MTW
dc.contributor.authorYang, L
dc.contributor.authorMyers, KA
dc.contributor.authorDeshmukh, N
dc.contributor.authorDenley, H
dc.contributor.authorBrowning, L
dc.contributor.authorLove, SB
dc.contributor.authorIyer, G
dc.contributor.authorClarke, NW
dc.contributor.authorHall, E
dc.contributor.authorHuddart, R
dc.contributor.authorJames, ND
dc.contributor.authorHoskin, PJ
dc.contributor.authorWest, CML
dc.contributor.authorKiltie, AE
dc.date.accessioned2019-03-26T14:57:30Z
dc.date.issued2019-07
dc.identifier.citationInternational journal of radiation oncology, biology, physics, 2019, 104 (4), pp. 809 - 818
dc.identifier.issn0360-3016
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3163
dc.identifier.eissn1879-355X
dc.identifier.doi10.1016/j.ijrobp.2019.03.015
dc.description.abstractPurpose Organ-confined muscle-invasive bladder cancer is treated with cystectomy or bladder preservation techniques, including radiation therapy. There are currently no biomarkers to inform management decisions and aid patient choice. Previously we showed high levels of MRE11 protein, assessed by immunohistochemistry (IHC), predicted outcome after radiation therapy, but not cystectomy. Therefore, we sought to develop the MRE11 IHC assay for clinical use and define its relationship to clinical outcome in samples from 2 major clinical trials.Methods and materials Samples from the BCON and BC2001 randomized controlled trials and a cystectomy cohort were stained using automated IHC methods and scored for MRE11 in 3 centers in the United Kingdom.Results Despite step-wise creation of scoring cards and standard operating procedures for staining and interpretation, there was poor intercenter scoring agreement (kappa, 0.32; 95% confidence interval, 0.17-0.47). No significant associations between MRE11 scores and cause-specific survival were identified in BCON (n = 132) and BC2001 (n = 221) samples. Reoptimized staining improved agreement between scores from BCON tissue microarrays (n = 116), but MRE11 expression was not prognostic for cause-specific survival.Conclusions Manual IHC scoring of MRE11 was not validated as a reproducible biomarker of radiation-based bladder preservation success. There is a need for automated quantitative methods or a reassessment of how DNA-damage response relates to clinical outcomes.
dc.formatPrint-Electronic
dc.format.extent809 - 818
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectTreatment Outcome
dc.subjectCystectomy
dc.subjectImmunohistochemistry
dc.subjectSurvival Analysis
dc.subjectProspective Studies
dc.subjectReproducibility of Results
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectUrinary Bladder Neoplasms
dc.subjectBiomarkers, Tumor
dc.subjectUnited Kingdom
dc.subjectMRE11 Homologue Protein
dc.titleMRE11 as a Predictive Biomarker of Outcome After Radiation Therapy in Bladder Cancer.
dc.typeJournal Article
dcterms.dateAccepted2019-03-09
rioxxterms.versionofrecord10.1016/j.ijrobp.2019.03.015
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2019-07
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfInternational journal of radiation oncology, biology, physics
pubs.issue4
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/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/ICR-CTSU Urology and Head and Neck Trials Team
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Clinical Academic Radiotherapy (Huddart)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Prostate and Bladder Cancer Research
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/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/ICR-CTSU Urology and Head and Neck Trials Team
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Clinical Academic Radiotherapy (Huddart)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Prostate and Bladder Cancer Research
pubs.publication-statusPublished
pubs.volume104
pubs.embargo.termsNo embargo
icr.researchteamICR-CTSU Urology and Head and Neck Trials Teamen_US
icr.researchteamClinical Academic Radiotherapy (Huddart)en_US
icr.researchteamProstate and Bladder Cancer Researchen_US
dc.contributor.icrauthorHall, Emmaen
dc.contributor.icrauthorHuddart, Roberten
dc.contributor.icrauthorJames, Nicholasen


Files in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record

https://creativecommons.org/licenses/by/4.0
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0