Abstract
ObjectivesThe aim was to explore the prognostic significance of IL-6 and markers of systemic inflammatory response (SIR), in particular C-reactive protein (CRP), in metastatic colorectal cancer (mCRC) patients, in the total study population and according to RAS and BRAF mutation status.ResultsHigh levels of pretreatment serum IL-6 or CRP were associated with impaired outcome, in terms of reduced PFS and OS. Patients with low versus high serum IL-6 levels had median OS of 26.0 versus 16.6 months, respectively (P < 0.001). Stratified according to increasing CRP levels, median OS varied from 24.3 months to 12.3 months, (P < 0.001). IL-6 and CRP levels affected overall prognosis also in adjusted analyses. The effect of IL-6 was particularly pronounced in patients with BRAF mutation (interaction P = 0.004).Materials and MethodsIL-6 and CRP were determined in pre-treatment serum samples from 393 patients included in the NORDIC-VII trial, in which patients with mCRC received first line treatment. The effect of serum IL-6 and CRP on progression-free survival (PFS) and overall survival (OS) was estimated.ConclusionsHigh baseline serum consentrations of IL-6 or CRP were associated with impaired prognosis in mCRC. IL-6 and CRP give independent prognostic information in addition to RAS and BRAF mutation status.
Highlights
Colorectal cancer (CRC) is worldwide the second most commonly diagnosed cancer in females and the third in males
High baseline serum consentrations of IL-6 or C-reactive protein (CRP) were associated with impaired prognosis in Metastatic CRC (mCRC)
Between May 2005 and October 2007, patients with untreated mCRC were enrolled in the NORDIC-VII study, randomized to first line treatment with standard Nordic FLOX, cetuximab and FLOX, or cetuximab combined with intermittent FLOX [39]
Summary
Colorectal cancer (CRC) is worldwide the second most commonly diagnosed cancer in females and the third in males. A large body of evidence indicates that an inflammatory microenvironment is of decisive importance for the progression of tumors and the clinical outcome of cancers [2,3,4,5,6], including CRC [7]. The stroma is the arena for numerous opposing stimulatory and inhibitory mechanisms [14,15,16,17], the very existence of the tumor reveals its escape from the host defense, and many lines of evidence strongly suggest that the microenvironment is largely tumor-promoting at all stages of cancer [2, 11, 18]
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