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dc.contributor.authorSmyth, ECen_US
dc.contributor.authorNyamundanda, Gen_US
dc.contributor.authorCunningham, Den_US
dc.contributor.authorFontana, Een_US
dc.contributor.authorRagulan, Cen_US
dc.contributor.authorTan, IBen_US
dc.contributor.authorLin, SJen_US
dc.contributor.authorWotherspoon, Aen_US
dc.contributor.authorNankivell, Men_US
dc.contributor.authorFassan, Men_US
dc.contributor.authorLampis, Aen_US
dc.contributor.authorHahne, JCen_US
dc.contributor.authorDavies, ARen_US
dc.contributor.authorLagergren, Jen_US
dc.contributor.authorGossage, JAen_US
dc.contributor.authorMaisey, Nen_US
dc.contributor.authorGreen, Men_US
dc.contributor.authorZylstra, JLen_US
dc.contributor.authorAllum, WHen_US
dc.contributor.authorLangley, REen_US
dc.contributor.authorTan, Pen_US
dc.contributor.authorValeri, Nen_US
dc.contributor.authorSadanandam, Aen_US
dc.coverage.spatialEnglanden_US
dc.date.accessioned2019-02-20T08:20:36Z
dc.date.issued2018-12-01en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/30481267en_US
dc.identifier5174347en_US
dc.identifier.citationAnn Oncol, 2018, 29 (12), pp. 2356 - 2362en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3073
dc.identifier.eissn1569-8041en_US
dc.identifier.doi10.1093/annonc/mdy407en_US
dc.description.abstractBackground: Following neoadjuvant chemotherapy for operable gastroesophageal cancer, lymph node metastasis is the only validated prognostic variable; however, within lymph node groups there is still heterogeneity with risk of relapse. We hypothesized that gene profiles from neoadjuvant chemotherapy treated resection specimens from gastroesophageal cancer patients can be used to define prognostic risk groups to identify patients at risk for relapse. Patients and methods: The Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial (n = 202 with high quality RNA) samples treated with perioperative chemotherapy were profiled for a custom gastric cancer gene panel using the NanoString platform. Genes associated with overall survival (OS) were identified using penalized and standard Cox regression, followed by generation of risk scores and development of a NanoString biomarker assay to stratify patients into risk groups associated with OS. An independent dataset served as a validation cohort. Results: Regression and clustering analysis of MAGIC patients defined a seven-Gene Signature and two risk groups with different OS [hazard ratio (HR) 5.1; P < 0.0001]. The median OS of high- and low-risk groups were 10.2 [95% confidence interval (CI) of 6.5 and 13.2 months] and 80.9 months (CI: 43.0 months and not assessable), respectively. Risk groups were independently prognostic of lymph node metastasis by multivariate analysis (HR 3.6 in node positive group, P = 0.02; HR 3.6 in high-risk group, P = 0.0002), and not prognostic in surgery only patients (n = 118; log rank P = 0.2). A validation cohort independently confirmed these findings. Conclusions: These results suggest that gene-based risk groups can independently predict prognosis in gastroesophageal cancer patients treated with neoadjuvant chemotherapy. This signature and associated assay may help risk stratify these patients for post-surgery chemotherapy in future perioperative chemotherapy-based clinical trials.en_US
dc.format.extent2356 - 2362en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.titleA seven-Gene Signature assay improves prognostic risk stratification of perioperative chemotherapy treated gastroesophageal cancer patients from the MAGIC trial.en_US
dc.typeJournal Article
rioxxterms.versionofrecord10.1093/annonc/mdy407en_US
rioxxterms.licenseref.startdate2018-12-01en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfAnn Oncolen_US
pubs.issue12en_US
pubs.notesNot knownen_US
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/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Gastrointestinal Cancer Biology and Genomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Systems and Precision Cancer Medicine
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublisheden_US
pubs.volume29en_US
pubs.embargo.termsNot knownen_US
icr.researchteamMedicine (RMH Smith Cunningham)en_US
icr.researchteamGastrointestinal Cancer Biology and Genomicsen_US
icr.researchteamSystems and Precision Cancer Medicineen_US
dc.contributor.icrauthorCunningham, Daviden_US
dc.contributor.icrauthorLampis, Andreaen_US
dc.contributor.icrauthorHahne, Jensen_US
dc.contributor.icrauthorValeri, Nicolaen_US
dc.contributor.icrauthorSadanandam, Angurajen_US
dc.contributor.icrauthorFontana, Elisaen_US


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