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dc.contributor.authorObulkasim, Aen_US
dc.contributor.authorYlstra, Ben_US
dc.contributor.authorvan Essen, HFen_US
dc.contributor.authorBenner, Cen_US
dc.contributor.authorStenning, Sen_US
dc.contributor.authorLangley, Ren_US
dc.contributor.authorAllum, Wen_US
dc.contributor.authorCunningham, Den_US
dc.contributor.authorInam, Ien_US
dc.contributor.authorHewitt, LCen_US
dc.contributor.authorWest, NPen_US
dc.contributor.authorMeijer, GAen_US
dc.contributor.authorvan de Wiel, MAen_US
dc.contributor.authorGrabsch, HIen_US
dc.identifier.citationOncotarget, 2016en_US
dc.description.abstractNeoadjuvant chemo(radio)therapy followed by surgery is the standard of care for patients with locally advanced resectable esophageal adenocarcinoma (EAC). There is increasing evidence that drug resistance might be related to genomic heterogeneity. We investigated whether genomic tumor heterogeneity is different after cytotoxic chemotherapy and is associated with EAC patient survival. We used arrayCGH and a quantitative assessment of the whole genome DNA copy number aberration patterns ('DNA copy number entropy') to establish the level of genomic tumor heterogeneity in 80 EAC treated with neoadjuvant chemotherapy followed by surgery (CS group) or surgery alone (S group). The association between DNA copy number entropy, clinicopathological variables and survival was investigated.DNA copy number entropy was reduced after chemotherapy, even if there was no morphological evidence of response to therapy (p<0.001). Low DNA copy number entropy was associated with improved survival in the CS group (p=0.011) but not in the S group (p=0.396).Our results suggest that cytotoxic chemotherapy reduces DNA copy number entropy, which might be a more sensitive tumor response marker than changes in the morphological tumor phenotype. The use of DNA copy number entropy in clinical practice will require validation of our results in a prospective study.en_US
dc.titleReduced genomic tumor heterogeneity after neoadjuvant chemotherapy is related to favorable outcome in patients with esophageal adenocarcinoma.en_US
dc.typeJournal Article
rioxxterms.typeJournal Article/Reviewen_US
pubs.notesNo embargoen_US
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.embargo.termsNo embargoen_US
icr.researchteamMedicine (RMH Smith Cunningham)en_US
dc.contributor.icrauthorCunningham, Daviden_US

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