Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/17399
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dc.contributor.authorPietrantonio, Filippo-
dc.contributor.authorDi Nicolantonio, Federica-
dc.contributor.authorSchrock, Alexa B-
dc.contributor.authorLee, Jeeyun-
dc.contributor.authorTejpar, Sabine-
dc.contributor.authorSartore-Bianchi, Andrea-
dc.contributor.authorHechtman, Jaclyn F-
dc.contributor.authorChristiansen, Jason-
dc.contributor.authorNovara, Luca-
dc.contributor.authorTebbutt, Niall C-
dc.contributor.authorFucà, Giovanni-
dc.contributor.authorAntoniotti, Carlotta-
dc.contributor.authorKim, Seung Tae-
dc.contributor.authorMurphy, Danielle-
dc.contributor.authorBerenato, Rosa-
dc.contributor.authorMorano, Federica-
dc.contributor.authorSun, James-
dc.contributor.authorMin, Bosun-
dc.contributor.authorStephens, Philip J-
dc.contributor.authorChen, Marissa-
dc.contributor.authorLazzari, Luca-
dc.contributor.authorMiller, Vincent A-
dc.contributor.authorShoemaker, Robert-
dc.contributor.authorAmatu, Alessio-
dc.contributor.authorMilione, Massimo-
dc.contributor.authorRoss, Jeffrey S-
dc.contributor.authorSiena, Salvatore-
dc.contributor.authorBardelli, Alberto-
dc.contributor.authorAli, Siraj M-
dc.contributor.authorFalcone, Alfredo-
dc.contributor.authorde Braud, Filippo-
dc.contributor.authorCremolini, Chiara-
dc.date.accessioned2018-04-11T01:10:42Z-
dc.date.available2018-04-11T01:10:42Z-
dc.date.issued2017-12-01-
dc.identifier.citationJournal of the National Cancer Institute 2017; 109(12): djx089-
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/17399-
dc.description.abstractALK, ROS1, and NTRK fusions occur in 0.2% to 2.4% of colorectal cancers. Pioneer cases of metastatic colorectal cancer (mCRC) patients bearing rearrangements who benefited from anti-ALK, ROS, and TrkA-B-C therapies have been reported previously. Here we aimed at characterizing the clinical and molecular landscape of ALK, ROS1, and NTRK rearranged mCRC. Clinical features and molecular characteristics of 27 mCRC patients bearing ALK, ROS1, and NTRK rearranged tumors were compared with those of a cohort of 319 patients not bearing rearrangements by means of Fisher's exact, χ2 test, or Mann-Whitney test as appropriate. Overall survival curves were estimated with the Kaplan-Meier method and compared using the log-rank test. A Cox proportional hazard model was adopted in the multivariable analysis. Deep molecular and immunophenotypic characterizations of rearranged cases, including those described in The Cancer Genome Atlas database, were performed. All statistical tests were two-sided. Closely recalling the "BRAF history," ALK, ROS1, and NTRK rearrangements more frequently occurred in elderly patients (P = .02) with right-sided tumors (P < .001) and node-spreading (P = .03), RAS wild-type (P < .001), and MSI-high (P < .001) cancers. All patients bearing ALK, ROS1, and NTRK fusions had shorter overall survival (15.6 months, 95% confidence interval [CI] = 0.0 to 20.4 months) than negative patients (33.7 months, 95% CI = 28.3 to 42.1 months), both in the univariate (hazard ratio [HR] = 2.17, 95% CI = 1.03 to 4.57, P < .001) and multivariable models (HR = 2.33, 95% CI = 1.10 to 4.95, P = .02). All four evaluable patients with rearrangements showed primary resistance to anti-epidermal growth factor receptor agents. Frequent association with potentially targetable RNF43 mutations was observed in MSI-high rearranged tumors. ALK, ROS1, and NTRK rearrangements define a new rare subtype of mCRC with extremely poor prognosis. Primary tumor site, MSI-high, and RAS and BRAF wild-type status may help to identify patients bearing these alterations. While sensitivity to available treatments is limited, targeted strategies inhibiting ALK, ROS, and TrkA-B-C provided encouraging results.-
dc.language.isoeng-
dc.titleALK, ROS1, and NTRK Rearrangements in Metastatic Colorectal Cancer.-
dc.typeJournal Article-
dc.identifier.journaltitleJournal of the National Cancer Institute-
dc.identifier.affiliationMedical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy-
dc.identifier.affiliationCandiolo Cancer Institute-FPO, IRCCS, Candiolo, Italyen
dc.identifier.affiliationFoundation Medicine, Inc., Cambridge, MA-
dc.identifier.affiliationSamsung Medical Center, Sungkyunkwan University School of Medicine, Kangnamgu, Seoul, Korea-
dc.identifier.affiliationMolecular Digestive Oncology Unit, University Hospital Gasthuisberg, Leuven, Belgium-
dc.identifier.affiliationNiguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy-
dc.identifier.affiliationMemorial Sloan Kettering Cancer Center, New York, New York, USA-
dc.identifier.affiliationIgnyta Inc., San Diego, CA..-
dc.identifier.affiliationDepartment of Oncology, University of Torino, Candiolo, Italy-
dc.identifier.affiliationAustin Health, Heidelberg, Victoria, Australia-
dc.identifier.affiliationAzienda Ospedaliero, Universitaria Pisana, Pisa, Italy-
dc.identifier.affiliationUniversity of Pisa, Pisa, Italy-
dc.identifier.doi10.1093/jnci/djx089-
dc.identifier.pubmedid29370427-
dc.type.austinJournal Article-
local.name.researcherTebbutt, Niall C
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.languageiso639-1en-
item.openairetypeJournal Article-
crisitem.author.deptMedical Oncology-
crisitem.author.deptOlivia Newton-John Cancer Wellness and Research Centre-
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