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dc.contributor.authorPietrantonio, F
dc.contributor.authorMiceli, R
dc.contributor.authorRaimondi, A
dc.contributor.authorKim, YW
dc.contributor.authorKang, WK
dc.contributor.authorLangley, RE
dc.contributor.authorChoi, YY
dc.contributor.authorKim, K-M
dc.contributor.authorNankivell, MG
dc.contributor.authorMorano, F
dc.contributor.authorWotherspoon, A
dc.contributor.authorValeri, N
dc.contributor.authorKook, M-C
dc.contributor.authorAn, JY
dc.contributor.authorGrabsch, HI
dc.contributor.authorFucà, G
dc.contributor.authorNoh, SH
dc.contributor.authorSohn, TS
dc.contributor.authorKim, S
dc.contributor.authorDi Bartolomeo, M
dc.contributor.authorCunningham, D
dc.contributor.authorLee, J
dc.contributor.authorCheong, J-H
dc.contributor.authorSmyth, EC
dc.date.accessioned2019-11-18T14:22:18Z
dc.date.issued2019-12
dc.identifier.citationJournal of clinical oncology : official journal of the American Society of Clinical Oncology, 2019, 37 (35), pp. 3392 - 3400
dc.identifier.issn0732-183X
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3424
dc.identifier.eissn1527-7755
dc.identifier.doi10.1200/jco.19.01124
dc.description.abstractPurpose In the CLASSIC and MAGIC trials, microsatellite instability (MSI)-high status was a favorable prognostic and potential negative predictive factor for neoadjuvant/adjuvant chemotherapy in resectable gastric cancer (GC). Given the low prevalence of MSI-high status in GC and its association with other positive prognostic variables, large data sets are needed to draw robust evidence of its prognostic/predictive value.Patients and methods We performed a multinational, individual-patient-data meta-analysis of the prognostic/predictive role of MSI in patients with resectable GC enrolled in the MAGIC, CLASSIC, ARTIST, and ITACA-S trials. Prognostic analyses used multivariable Cox models (MVM). The predictive role of MSI was assessed both in an all-comer population and in MAGIC and CLASSIC trials by MVM testing of the interaction of treatment (chemotherapy plus surgery v surgery) with MSI.Results MSI status was available for 1,556 patients: 121 (7.8%) had MSI-high status; 576 were European, and 980 were Asian. In MSI-high versus MSI-low/microsatellite stable (MSS) comparisons, the 5-year disease-free survival (DFS) was 71.8% (95% CI, 63.8% to 80.7%) versus 52.3% (95% CI, 49.7% to 55.1%); the 5-year overall survival (OS) was 77.5% (95% CI, 70.0% to 85.8%) versus 59.3% (95% CI, 56.6% to 62.1%). In MVM, MSI was associated with longer DFS (hazard ratio [HR], 1.88; 95% CI, 1.28 to 2.76; P < .001) and OS (HR, 1.78; 95% CI, 1.17 to 2.73; P = .008), as were pT, pN, ethnicity, and treatment. Patients with MSI-low/MSS GC benefitted from chemotherapy plus surgery: the 5-year DFS compared with surgery only was 57% versus 41% (HR, 0.65; 95% CI, 0.53 to 0.79), and the 5-year OS was 62% versus 53% (HR, 0.75; 95% CI, 0.60 to 0.94). Conversely, those with MSI-high GC did not: the 5-year DFS was 70% versus 77% (HR, 1.27; 95% CI, 0.53 to 3.04), and the 5-year OS was 75% versus 83% (HR, 1.50; 95% CI, 0.55 to 4.12).Conclusion In patients with resectable primary GC, MSI is a robust prognostic marker that should be adopted as a stratification factor by clinical trials. Chemotherapy omission and/or immune checkpoint blockade should be investigated prospectively in MSI-high GCs according to clinically and pathologically defined risk of relapse.
dc.formatPrint-Electronic
dc.format.extent3392 - 3400
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
dc.subjectHumans
dc.subjectStomach Neoplasms
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectPrognosis
dc.subjectChemotherapy, Adjuvant
dc.subjectSurvival Rate
dc.subjectFollow-Up Studies
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectMicrosatellite Instability
dc.subjectYoung Adult
dc.subjectBiomarkers, Tumor
dc.subjectPrecision Medicine
dc.titleIndividual Patient Data Meta-Analysis of the Value of Microsatellite Instability As a Biomarker in Gastric Cancer.
dc.typeJournal Article
rioxxterms.versionofrecord10.1200/jco.19.01124
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
rioxxterms.licenseref.startdate2019-12
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfJournal of clinical oncology : official journal of the American Society of Clinical Oncology
pubs.issue35
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.volume37
pubs.embargo.termsNot known
icr.researchteamMedicine (RMH Smith Cunningham)en_US
icr.researchteamGastrointestinal Cancer Biology and Genomicsen_US
dc.contributor.icrauthorCunningham, Daviden
dc.contributor.icrauthorValeri, Nicolaen


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