PI3K pathway mutations are associated with longer time to local progression after radioembolization of colorectal liver metastases

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dc.contributor.authorZiv, Etayen
dc.contributor.authorBergen, Michaelen
dc.contributor.authorYarmohammadi, Hoomanen
dc.contributor.authorBoas, F. Eden
dc.contributor.authorPetre, E. Nadiaen
dc.contributor.authorSofocleous, Constantinos T.en
dc.contributor.authorYaeger, Ronaen
dc.contributor.authorSolit, David B.en
dc.contributor.authorSolomon, Stephen B.en
dc.contributor.authorErinjeri, Joseph P.en
dc.date.accessioned2022-06-24T17:08:56Zen
dc.date.available2022-06-24T17:08:56Zen
dc.date.issued2017-04-04en
dc.date.updated2022-06-24T16:00:40Zen
dc.description.abstractPurpose: To establish the relationship between common mutations in the MAPK and PI3K signaling pathways and local progression after radioembolization. Materials and methods: Retrospective review of a HIPAA-compliant institutional review-board approved database identified 40 patients with chemo-refractory colorectal liver metastases treated with radioembolization who underwent tumor genotyping for hotspot mutations in 6 key genes in the MAPK/PI3K pathways (KRAS, NRAS, BRAF, MEK1, PIK3CA, and AKT1). Mutation status as well as clinical, tumor, and treatment variables were recorded. These factors were evaluated in relation to time to local progression (TTLP), which was calculated from time of radioembolization to first radiographic evidence of local progression. Predictors of outcome were identified using a proportional hazards model for both univariate and multivariate analysis with death as a competing risk. Results: Sixteen patients (40%) had no mutations in either pathway, eighteen patients (45%) had mutations in the MAPK pathway, ten patients (25%) had mutations in the PI3K pathway and four patients (10%) had mutations in both pathways. The cumulative incidence of progression at 6 and 12 months was 33% and 55% for the PI3K mutated group compared with 76% and 92% in the PI3K wild type group. Mutation in the PI3K pathway was a significant predictor of longer TTLP in both univariate (p=0.031, sHR 0.31, 95% CI: 0.11-0.90) and multivariate (p=0.015, sHR=0.27, 95% CI: 0.096-0.77) analysis. MAPK pathway alterations were not associated with TTLP. Conclusions: PI3K pathway mutation predicts longer time to local progression after radioembolization of colorectal liver metastases.en
dc.description.versionPublished versionen
dc.format.extentPages 23529-23538en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.18632/oncotarget.15278en
dc.identifier.eissn1949-2553en
dc.identifier.issn1949-2553en
dc.identifier.issue14en
dc.identifier.otherPMC5410324en
dc.identifier.other15278 (PII)en
dc.identifier.pmid28206962en
dc.identifier.urihttp://hdl.handle.net/10919/110933en
dc.identifier.volume8en
dc.language.isoenen
dc.publisherOncotargeten
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/28206962en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectMAPKen
dc.subjectPI3Ken
dc.subjectbiomarkersen
dc.subjectcolorectalen
dc.subjectradioembolizationen
dc.subject.meshHumansen
dc.subject.meshColorectal Neoplasmsen
dc.subject.meshLiver Neoplasmsen
dc.subject.meshDisease Progressionen
dc.subject.meshPrognosisen
dc.subject.meshEmbolization, Therapeuticen
dc.subject.meshRadiotherapyen
dc.subject.meshMultivariate Analysisen
dc.subject.meshProportional Hazards Modelsen
dc.subject.meshRetrospective Studiesen
dc.subject.meshSignal Transductionen
dc.subject.meshMutationen
dc.subject.meshTime Factorsen
dc.subject.meshAdulten
dc.subject.meshAgeden
dc.subject.meshAged, 80 and overen
dc.subject.meshMiddle Ageden
dc.subject.meshFemaleen
dc.subject.meshMaleen
dc.subject.meshPhosphatidylinositol 3-Kinasesen
dc.subject.meshOutcome Assessment, Health Careen
dc.titlePI3K pathway mutations are associated with longer time to local progression after radioembolization of colorectal liver metastasesen
dc.title.serialOncotargeten
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dcterms.dateAccepted2017-01-16en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicineen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicine/Radiologyen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicine/Radiology/Interventional Radiologyen

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