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dc.contributor.authorSmyth, ECen_US
dc.contributor.authorWotherspoon, Aen_US
dc.contributor.authorPeckitt, Cen_US
dc.contributor.authorGonzalez, Den_US
dc.contributor.authorHulkki-Wilson, Sen_US
dc.contributor.authorEltahir, Zen_US
dc.contributor.authorFassan, Men_US
dc.contributor.authorRugge, Men_US
dc.contributor.authorValeri, Nen_US
dc.contributor.authorOkines, Aen_US
dc.contributor.authorHewish, Men_US
dc.contributor.authorAllum, Wen_US
dc.contributor.authorStenning, Sen_US
dc.contributor.authorNankivell, Men_US
dc.contributor.authorLangley, Ren_US
dc.contributor.authorCunningham, Den_US
dc.date.accessioned2017-10-31T11:57:20Z
dc.date.issued2017-09en_US
dc.identifier.citationJAMA oncology, 2017, 3 (9), pp. 1197 - 1203en_US
dc.identifier.issn2374-2437en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/879
dc.identifier.eissn2374-2445en_US
dc.identifier.doi10.1001/jamaoncol.2016.6762en_US
dc.description.abstract<h4>Importance</h4>Mismatch repair (MMR) deficiency (MMRD) and microsatellite instability (MSI) are prognostic for survival in many cancers and for resistance to fluoropyrimidines in early colon cancer. However, the effect of MMRD and MSI in curatively resected gastric cancer treated with perioperative chemotherapy is unknown.<h4>Objective</h4>To examine the association among MMRD, MSI, and survival in patients with resectable gastroesophageal cancer randomized to surgery alone or perioperative epirubicin, cisplatin, and fluorouracil chemotherapy in the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial.<h4>Design, setting, and participants</h4>This secondary post hoc analysis of the MAGIC trial included participants who were treated with surgery alone or perioperative chemotherapy plus surgery for operable gastroesophageal cancer from July 1, 1994, through April 30, 2002. Tumor sections were assessed for expression of the MMR proteins mutL homologue 1, mutS homologue 2, mutS homologue 6, and PMS1 homologue 2. The association among MSI, MMRD, and survival was assessed.<h4>Main outcomes and measures</h4>Interaction between MMRD and MSI status and overall survival (OS).<h4>Results</h4>Of the 503 study participants, MSI results were available for 303 patients (283 with microsatellite stability or low MSI [median age, 62 years; 219 males (77.4%)] and 20 with high MSI [median age, 66 years; 14 males (70.0%)]). A total of 254 patients had MSI and MMR results available. Patients treated with surgery alone who had high MSI or MMRD had a median OS that was not reached (95% CI, 11.5 months to not reached) compared with a median OS among those who had neither high MSI nor MMRD of 20.5 months (95% CI, 16.7-27.8 months; hazard ratio, 0.42; 95% CI, 0.15-1.15; P = .09). In contrast, patients treated with chemotherapy plus surgery who had either high MSI or MMRD had a median OS of 9.6 months (95% CI, 0.1-22.5 months) compared with a median OS among those who were neither high MSI nor MMRD of 19.5 months (95% CI, 15.4-35.2 months; hazard ratio, 2.18; 95% CI, 1.08-4.42; P = .03).<h4>Conclusions and relevance</h4>In the MAGIC trial, MMRD and high MSI were associated with a positive prognostic effect in patients treated with surgery alone and a differentially negative prognostic effect in patients treated with chemotherapy. If independently validated, MSI or MMRD determined by preoperative biopsies could be used to select patients for perioperative chemotherapy.en_US
dc.formatPrinten_US
dc.format.extent1197 - 1203en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://www.rioxx.net/licenses/under-embargo-all-rights-reserveden_US
dc.subjectHumansen_US
dc.subjectStomach Neoplasmsen_US
dc.subjectCisplatinen_US
dc.subjectFluorouracilen_US
dc.subjectEpirubicinen_US
dc.subjectDNA-Binding Proteinsen_US
dc.subjectAntineoplastic Combined Chemotherapy Protocolsen_US
dc.subjectPrognosisen_US
dc.subjectChemotherapy, Adjuvanten_US
dc.subjectGastrectomyen_US
dc.subjectSurvival Rateen_US
dc.subjectAdulten_US
dc.subjectAgeden_US
dc.subjectMiddle Ageden_US
dc.subjectFemaleen_US
dc.subjectMaleen_US
dc.subjectMutS Homolog 2 Proteinen_US
dc.subjectMicrosatellite Instabilityen_US
dc.subjectDNA Mismatch Repairen_US
dc.subjectMutL Protein Homolog 1en_US
dc.subjectMismatch Repair Endonuclease PMS2en_US
dc.titleMismatch Repair Deficiency, Microsatellite Instability, and Survival: An Exploratory Analysis of the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) Trial.en_US
dc.typeJournal Article
dcterms.dateAccepted2016-11-30en_US
rioxxterms.funderThe Institute of Cancer Researchen_US
rioxxterms.identifier.projectUnspecifieden_US
rioxxterms.versionofrecord10.1001/jamaoncol.2016.6762en_US
rioxxterms.licenseref.startdate2017-09en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfJAMA oncologyen_US
pubs.issue9en_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/Royal Marsden Clinical Units
pubs.publication-statusPublisheden_US
pubs.volume3en_US
pubs.embargo.termsNot knownen_US
icr.researchteamMedicine (RMH Smith Cunningham)en_US
icr.researchteamGastrointestinal Cancer Biology and Genomicsen_US
dc.contributor.icrauthorCunningham, Daviden_US
dc.contributor.icrauthorValeri, Nicolaen_US
dc.contributor.icrauthorSmyth, Lizzyen_US
dc.contributor.icrauthorMarsden,en_US
rioxxterms.funder.project354849bd-c553-4e22-868c-8c503e124155en_US


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