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dc.contributor.authorSmyth, EC
dc.contributor.authorWotherspoon, A
dc.contributor.authorPeckitt, C
dc.contributor.authorGonzalez, D
dc.contributor.authorHulkki-Wilson, S
dc.contributor.authorEltahir, Z
dc.contributor.authorFassan, M
dc.contributor.authorRugge, M
dc.contributor.authorValeri, N
dc.contributor.authorOkines, A
dc.contributor.authorHewish, M
dc.contributor.authorAllum, W
dc.contributor.authorStenning, S
dc.contributor.authorNankivell, M
dc.contributor.authorLangley, R
dc.contributor.authorCunningham, D
dc.date.accessioned2017-10-31T11:57:20Z
dc.date.issued2017-09-01
dc.identifier.citationJAMA oncology, 2017, 3 (9), pp. 1197 - 1203
dc.identifier.issn2374-2437
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/879
dc.identifier.eissn2374-2445
dc.identifier.doi10.1001/jamaoncol.2016.6762
dc.description.abstractIMPORTANCE: 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. OBJECTIVE: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. MAIN OUTCOMES AND MEASURES: Interaction between MMRD and MSI status and overall survival (OS). RESULTS: 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). CONCLUSIONS AND RELEVANCE: 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.
dc.formatPrint
dc.format.extent1197 - 1203
dc.languageeng
dc.language.isoeng
dc.publisherAMER MEDICAL ASSOC
dc.rights.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
dc.subjectHumans
dc.subjectStomach Neoplasms
dc.subjectCisplatin
dc.subjectFluorouracil
dc.subjectEpirubicin
dc.subjectDNA-Binding Proteins
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectPrognosis
dc.subjectChemotherapy, Adjuvant
dc.subjectGastrectomy
dc.subjectSurvival Rate
dc.subjectAdult
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectMutS Homolog 2 Protein
dc.subjectMicrosatellite Instability
dc.subjectDNA Mismatch Repair
dc.subjectMutL Protein Homolog 1
dc.subjectMismatch Repair Endonuclease PMS2
dc.titleMismatch Repair Deficiency, Microsatellite Instability, and Survival: An Exploratory Analysis of the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) Trial.
dc.typeJournal Article
dcterms.dateAccepted2016-11-30
rioxxterms.funderThe Institute of Cancer Research
rioxxterms.identifier.projectUnspecified
rioxxterms.versionofrecord10.1001/jamaoncol.2016.6762
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
rioxxterms.licenseref.startdate2017-09
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfJAMA oncology
pubs.issue9
pubs.notesNot 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/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.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-statusPublished
pubs.volume3
pubs.embargo.termsNot known
icr.researchteamMedicine (RMH Smith Cunningham)
icr.researchteamGastrointestinal Cancer Biology and Genomics
dc.contributor.icrauthorValeri, Nicola


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