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dc.contributor.authorHale, MD
dc.contributor.authorNankivell, M
dc.contributor.authorHutchins, GG
dc.contributor.authorStenning, SP
dc.contributor.authorLangley, RE
dc.contributor.authorMueller, W
dc.contributor.authorWest, NP
dc.contributor.authorWright, AI
dc.contributor.authorTreanor, D
dc.contributor.authorHewitt, LC
dc.contributor.authorAllum, WH
dc.contributor.authorCunningham, D
dc.contributor.authorHayden, JD
dc.contributor.authorGrabsch, HI
dc.date.accessioned2017-01-04T13:14:13Z
dc.date.issued2016-11
dc.identifier.citationOncotarget, 2016, 7 (47), pp. 77565 - 77575
dc.identifier.issn1949-2553
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/360
dc.identifier.eissn1949-2553
dc.identifier.doi10.18632/oncotarget.12723
dc.description.abstractBackground Neoadjuvant chemotherapy followed by surgery is the standard of care for UK patients with locally advanced resectable oesophageal carcinoma (OeC). However, not all patients benefit from multimodal treatment and there is a clinical need for biomarkers which can identify chemotherapy responders. This study investigated whether the proportion of tumour cells per tumour area (PoT) measured in the pre-treatment biopsy predicts chemotherapy benefit for OeC patients.Patients and methods PoT was quantified using digitized haematoxylin/eosin stained pre-treatment biopsy slides from 281 OeC patients from the UK MRC OE02 trial (141 treated by surgery alone (S); 140 treated by 5-fluorouracil/cisplatin followed by surgery (CS)). The relationship between PoT and clinicopathological data including tumour regression grade (TRG), overall survival and treatment interaction was investigated.Results PoT was associated with chemotherapy benefit in a non-linear fashion (test for interaction, P=0.006). Only patients with a biopsy PoT between 40% and 70% received a significant survival benefit from neoadjuvant chemotherapy (N=129; HR (95%CI):1.94 (1.39-2.71), unlike those with lower or higher PoT (PoT<40%, N=39, HR:1.25 (0.66-2.35); PoT>70% (N=28, HR:0.65 (0.36-1.18)). High pre-treatment PoT was related to lack of primary tumour regression (TRG 4 or 5), P=0.0402.Conclusions This is the first study to identify in a representative subgroup of OeC patients from a large randomized phase III trial that the proportion of tumour in the pre-chemotherapy biopsy predicts benefit from chemotherapy and may be a clinically useful biomarker for patient treatment stratification.Proportion of tumour is a novel biomarker which can be measured in the pre-treatment diagnostic biopsy and which may enable the identification of chemotherapy responders and non-responders among patients with oesophageal carcinoma. Proportion of tumour could easily become part of the routine reporting of oesophageal cancer biopsies and may aid in managing patients with borderline resectable cancer.
dc.formatPrint
dc.format.extent77565 - 77575
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectEsophageal Neoplasms
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectBiopsy
dc.subjectPrognosis
dc.subjectCombined Modality Therapy
dc.subjectSurvival Analysis
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectClinical Trials as Topic
dc.subjectNeoplasm Grading
dc.titleBiopsy proportion of tumour predicts pathological tumour response and benefit from chemotherapy in resectable oesophageal carcinoma: results from the UK MRC OE02 trial.
dc.typeJournal Article
dcterms.dateAccepted2016-10-01
rioxxterms.versionofrecord10.18632/oncotarget.12723
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2016-11
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfOncotarget
pubs.issue47
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/Medicine (RMH Smith Cunningham)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)/Medicine (RMH Smith Cunningham) (hon.)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
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/Medicine (RMH Smith Cunningham)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)/Medicine (RMH Smith Cunningham) (hon.)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume7
pubs.embargo.termsNo embargo
icr.researchteamMedicine (RMH Smith Cunningham)en_US
dc.contributor.icrauthorCunningham, Daviden


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