• Susanna Hegewisch-Becker, Stefanie Nöpel-Dünnebacke, Axel Hinke, Ullrich Graeven, Anke Reinacher-Schick, Jan Hertel, Christian A Lerchenmüller, Birgitta Killing, Reinhard Depenbusch, Salah-Eddin Al-Batran, Thoralf Lange, Georg Dietrich, Andrea Tannapfel, and Dirk Arnold.
• HOPE - Practice for Oncology, Hamburg, Germany.
• Eur. J. Cancer. 2018 Sep 1; 101: 105-113.

BackgroundThe major prognostic relevance of primary tumour location (LPT) in advanced colorectal cancer was shown in large retrospective studies, but quantitative estimates are highly heterogeneous, and there is still limited information about its impact within the framework of biomarker-guided treatment strategies. Therefore, we analysed LPT in relation to other clinical and molecular parameters, based on mature survival data from the recent randomised AIO KRK0207 trial.MethodsPatients uniformly received first-line induction treatment with a combination of bevacizumab, oxaliplatin and fluoropyrimidine. LPT was retrospectively determined using surgical reports, pathology reports and endoscopy reports. The prognostic analyses were performed using Kaplan-Meier estimations and log-rank tests, while hazard ratios (HRs) and multivariable results were derived from Cox models.ResultsAmong 754 patients with unequivocal information on LPT, patients with left-sided tumours showed a median overall survival of 24.8 months compared with the right-sided cohort with 18.4 months (HR: 1.54, 95% confidence interval: 1.30-1.81, P < 0.0001). In a multivariable model, LPT proved to be the strongest prognosticator (HR 1.60), with performance status, number of metastatic sites, baseline carcinoembryonic antigen (CEA) and platelets independently retaining prognostic significance. In the subgroup of patients with known RAS/BRAF status (n = 567, 75%), a BRAF mutation showed the greatest unfavourable impact (HR 3.16). Although BRAF is strongly correlated to LPT, the latter remained a significant prognosticator in the BRAF wild-type subgroup. In contrast, no major impact of LPT was seen on tumours carrying RAS mutations.ConclusionsWithin the framework of a uniform treatment strategy according to the current standards, LPT proved to have an important, although not solely dominating, relevance for survival prognosis. Its impact seems to be low in tumours with a RAS mutation.RegistrationClinicalTrials.govNCT00973609.Copyright © 2018 Elsevier Ltd. All rights reserved.

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