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dc.contributor.authorKayhanian, H
dc.contributor.authorGoode, E
dc.contributor.authorSclafani, F
dc.contributor.authorAng, JE
dc.contributor.authorGerlinger, M
dc.contributor.authorGonzalez de Castro, D
dc.contributor.authorShepherd, S
dc.contributor.authorPeckitt, C
dc.contributor.authorRao, S
dc.contributor.authorWatkins, D
dc.contributor.authorChau, I
dc.contributor.authorCunningham, D
dc.contributor.authorStarling, N
dc.date.accessioned2018-02-15T12:24:16Z
dc.date.issued2018-03
dc.identifier.citationClinical colorectal cancer, 2018, 17 (1), pp. e69 - e76
dc.identifier.issn1533-0028
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1117
dc.identifier.eissn1938-0674
dc.identifier.doi10.1016/j.clcc.2017.10.006
dc.description.abstractBackground Somatic v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutation, present in approximately 10% of metastatic colorectal cancer (mCRC) cases, is associated with poor prognosis. Patient outcome outside of clinical trials has only been reported in small series. We report real-world data on treatment and survival for BRAF-mutated (MT) patients at a single tertiary center, compared with a matched BRAF wild type (WT) control group.Patients and methods All colorectal cancer patients tested for BRAF mutation, from October 2010 to November 2014 were identified. BRAF-MT mCRC cases were compared with an age and sex-matched BRAF-WT control group. Clinicopathological data were collected and survival calculated using the Kaplan-Meier method and comparisons made using Cox regression.Results Forty-three of 503 patients (8.5%) tested had BRAF-MT mCRC and were compared with 88 BRAF-WT controls. Median overall survival (mOS) was 18.2 months for BRAF-MT and 41.1 months for BRAF-WT mCRC patients (hazard ratio, 2.74; 95% confidence interval, 1.60-4.70; P < .001). Progression-free survival for BRAF-MT and WT patients, respectively, was: 8.1 months versus 9.2 months (P = .571) first-line, 5.5 months versus 8.3 months (P = .074) second-line, and 1.8 months versus 5.6 months (P = .074) third-line. Treatment using sequential fluoropyrimidine-based doublet chemotherapy was similar between both groups. Anti-epidermal growth factor receptor (EGFR) therapy was mainly given third-line with progressive disease in 90% (n = 9 of 10) of BRAF-MT patients at first restaging.Conclusion In this case-control study, the poor mOS of BRAF-MT mCRC was associated with reduced treatment benefit beyond first-line. Sequential doublet chemotherapy remains a reasonable option in appropriately selected patients. BRAF-MT patients did not benefit from anti-EGFR therapy in this study. Recruitment to clinical trials is recommended to improve outcomes in BRAF-MT mCRC.
dc.formatPrint-Electronic
dc.format.extente69 - e76
dc.languageeng
dc.language.isoeng
dc.subjectHumans
dc.subjectColorectal Neoplasms
dc.subjectProto-Oncogene Proteins B-raf
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectTreatment Outcome
dc.subjectProportional Hazards Models
dc.subjectCase-Control Studies
dc.subjectRetrospective Studies
dc.subjectMutation
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectKaplan-Meier Estimate
dc.subjectProgression-Free Survival
dc.titleTreatment and Survival Outcome of BRAF-Mutated Metastatic Colorectal Cancer: A Retrospective Matched Case-Control Study.
dc.typeJournal Article
dcterms.dateAccepted2017-10-10
rioxxterms.versionofrecord10.1016/j.clcc.2017.10.006
rioxxterms.licenseref.startdate2018-03
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfClinical colorectal cancer
pubs.issue1
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/Gastrointestinal Cancers Clinical Trials
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Gastrointestinal Cancers Clinical Trials/Gastrointestinal Cancers Clinical Trials (hon.)
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/Translational Oncogenomics
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/Gastrointestinal Cancers Clinical Trials
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Gastrointestinal Cancers Clinical Trials/Gastrointestinal Cancers Clinical Trials (hon.)
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/Translational Oncogenomics
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume17
pubs.embargo.termsNot known
icr.researchteamGastrointestinal Cancers Clinical Trialsen_US
icr.researchteamMedicine (RMH Smith Cunningham)en_US
icr.researchteamTranslational Oncogenomicsen_US
dc.contributor.icrauthorCunningham, Daviden
dc.contributor.icrauthorGerlinger, Marcoen
dc.contributor.icrauthorChau, Ianen
dc.contributor.icrauthorStarling, Naureenen
dc.contributor.icrauthorMarsden,en


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