dc.contributor.author | Turkington, RC | |
dc.contributor.author | Knight, LA | |
dc.contributor.author | Blayney, JK | |
dc.contributor.author | Secrier, M | |
dc.contributor.author | Douglas, R | |
dc.contributor.author | Parkes, EE | |
dc.contributor.author | Sutton, EK | |
dc.contributor.author | Stevenson, L | |
dc.contributor.author | McManus, D | |
dc.contributor.author | Halliday, S | |
dc.contributor.author | McCavigan, AM | |
dc.contributor.author | Logan, GE | |
dc.contributor.author | Walker, SM | |
dc.contributor.author | Steele, CJ | |
dc.contributor.author | Perner, J | |
dc.contributor.author | Bornschein, J | |
dc.contributor.author | MacRae, S | |
dc.contributor.author | Miremadi, A | |
dc.contributor.author | McCarron, E | |
dc.contributor.author | McQuaid, S | |
dc.contributor.author | Arthur, K | |
dc.contributor.author | James, JA | |
dc.contributor.author | Eatock, MM | |
dc.contributor.author | O'Neill, R | |
dc.contributor.author | Noble, F | |
dc.contributor.author | Underwood, TJ | |
dc.contributor.author | Harkin, DP | |
dc.contributor.author | Salto-Tellez, M | |
dc.contributor.author | Fitzgerald, RC | |
dc.contributor.author | Kennedy, RD | |
dc.contributor.author | Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Study Group, | |
dc.date.accessioned | 2020-08-28T09:01:36Z | |
dc.date.issued | 2019-11-01 | |
dc.identifier.citation | Gut, 2019, 68 (11), pp. 1918 - 1927 | |
dc.identifier.issn | 0017-5749 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4047 | |
dc.identifier.eissn | 1468-3288 | |
dc.identifier.doi | 10.1136/gutjnl-2018-317624 | |
dc.description.abstract | OBJECTIVE: 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.format | Print-Electronic | |
dc.format.extent | 1918 - 1927 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | BMJ PUBLISHING GROUP | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0 | |
dc.subject | Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Study Group | |
dc.subject | CD8-Positive T-Lymphocytes | |
dc.subject | Humans | |
dc.subject | Adenocarcinoma | |
dc.subject | Esophageal Neoplasms | |
dc.subject | DNA Damage | |
dc.subject | Antineoplastic Agents | |
dc.subject | Disease-Free Survival | |
dc.subject | Treatment Outcome | |
dc.subject | Chemotherapy, Adjuvant | |
dc.subject | Neoadjuvant Therapy | |
dc.subject | Esophagectomy | |
dc.subject | Survival Rate | |
dc.subject | Predictive Value of Tests | |
dc.subject | Aged | |
dc.subject | Middle Aged | |
dc.subject | Female | |
dc.subject | Male | |
dc.subject | B7-H1 Antigen | |
dc.title | Immune activation by DNA damage predicts response to chemotherapy and survival in oesophageal adenocarcinoma. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2019-02-15 | |
rioxxterms.versionofrecord | 10.1136/gutjnl-2018-317624 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by-nc/4.0 | |
rioxxterms.licenseref.startdate | 2019-11 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Gut | |
pubs.issue | 11 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 68 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Integrated Pathology | |
dc.contributor.icrauthor | Salto-Tellez, Manuel | |