Show simple item record

dc.contributor.authorTurkington, RC
dc.contributor.authorKnight, LA
dc.contributor.authorBlayney, JK
dc.contributor.authorSecrier, M
dc.contributor.authorDouglas, R
dc.contributor.authorParkes, EE
dc.contributor.authorSutton, EK
dc.contributor.authorStevenson, L
dc.contributor.authorMcManus, D
dc.contributor.authorHalliday, S
dc.contributor.authorMcCavigan, AM
dc.contributor.authorLogan, GE
dc.contributor.authorWalker, SM
dc.contributor.authorSteele, CJ
dc.contributor.authorPerner, J
dc.contributor.authorBornschein, J
dc.contributor.authorMacRae, S
dc.contributor.authorMiremadi, A
dc.contributor.authorMcCarron, E
dc.contributor.authorMcQuaid, S
dc.contributor.authorArthur, K
dc.contributor.authorJames, JA
dc.contributor.authorEatock, MM
dc.contributor.authorO'Neill, R
dc.contributor.authorNoble, F
dc.contributor.authorUnderwood, TJ
dc.contributor.authorHarkin, DP
dc.contributor.authorSalto-Tellez, M
dc.contributor.authorFitzgerald, RC
dc.contributor.authorKennedy, RD
dc.contributor.authorOesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Study Group
dc.date.accessioned2020-08-28T09:01:36Z
dc.date.issued2019-11
dc.identifier.citationGut, 2019, 68 (11), pp. 1918 - 1927
dc.identifier.issn0017-5749
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4047
dc.identifier.eissn1468-3288
dc.identifier.doi10.1136/gutjnl-2018-317624
dc.description.abstractObjective Current strategies to guide selection of neoadjuvant therapy in oesophageal adenocarcinoma (OAC) are inadequate. We assessed the ability of a DNA damage immune response (DDIR) assay to predict response following neoadjuvant chemotherapy in OAC.Design Transcriptional profiling of 273 formalin-fixed paraffin-embedded prechemotherapy endoscopic OAC biopsies was performed. All patients were treated with platinum-based neoadjuvant chemotherapy and resection between 2003 and 2014 at four centres in the Oesophageal Cancer Clinical and Molecular Stratification consortium. CD8 and programmed death ligand 1 (PD-L1) immunohistochemical staining was assessed in matched resection specimens from 126 cases. Kaplan-Meier and Cox proportional hazards regression analysis were applied according to DDIR status for recurrence-free survival (RFS) and overall survival (OS).Results A total of 66 OAC samples (24%) were DDIR positive with the remaining 207 samples (76%) being DDIR negative. DDIR assay positivity was associated with improved RFS (HR: 0.61; 95% CI 0.38 to 0.98; p=0.042) and OS (HR: 0.52; 95% CI 0.31 to 0.88; p=0.015) following multivariate analysis. DDIR-positive patients had a higher pathological response rate (p=0.033), lower nodal burden (p=0.026) and reduced circumferential margin involvement (p=0.007). No difference in OS was observed according to DDIR status in an independent surgery-alone dataset.DDIR-positive OAC tumours were also associated with the presence of CD8+ lymphocytes (intratumoural: p<0.001; stromal: p=0.026) as well as PD-L1 expression (intratumoural: p=0.047; stromal: p=0.025).Conclusion The DDIR assay is strongly predictive of benefit from DNA-damaging neoadjuvant chemotherapy followed by surgical resection and is associated with a proinflammatory microenvironment in OAC.
dc.formatPrint-Electronic
dc.format.extent1918 - 1927
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
dc.subjectOesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Study Group
dc.subjectCD8-Positive T-Lymphocytes
dc.subjectHumans
dc.subjectAdenocarcinoma
dc.subjectEsophageal Neoplasms
dc.subjectDNA Damage
dc.subjectAntineoplastic Agents
dc.subjectDisease-Free Survival
dc.subjectTreatment Outcome
dc.subjectChemotherapy, Adjuvant
dc.subjectNeoadjuvant Therapy
dc.subjectEsophagectomy
dc.subjectSurvival Rate
dc.subjectPredictive Value of Tests
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectB7-H1 Antigen
dc.titleImmune activation by DNA damage predicts response to chemotherapy and survival in oesophageal adenocarcinoma.
dc.typeJournal Article
dcterms.dateAccepted2019-02-15
rioxxterms.versionofrecord10.1136/gutjnl-2018-317624
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc/4.0
rioxxterms.licenseref.startdate2019-11
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfGut
pubs.issue11
pubs.notesNot known
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/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Integrated Pathology
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/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Integrated Pathology
pubs.publication-statusPublished
pubs.volume68
pubs.embargo.termsNot known
icr.researchteamIntegrated Pathologyen_US
dc.contributor.icrauthorSalto-Tellez, Manuelen


Files in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record

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