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Background: In spite of demonstrating prognostic and possibly predictive benefit in retrospective cohorts and meta-analyses of cancer populations, including colorectal cancer (CRC), prospective evaluation of the relationship between neutrophil to lymphocyte ratio (NLR) and treatment outcomes in previously untreated mCRC patients receiving bevacizumab-based therapy has not yet been performed. Methods: An open-label, single arm, multi-centre study. Patients received first-line bevacizumab plus XELOX or mFOLFOX6 (Phase-A) and continued bevacizumab plus FOLFIRI beyond first progression (Phase-B). Analyses included the association of NLR with phase A progression free survival (PFS) and overall survival (OS). A sub-study investigated the safety in patients with the primary in situ tumor. An exploratory sub-study examined relationships of circulating proteomic markers with PFS. Results: Phase-A enrolled 128 patients; median age was 64 years (range: 26–84), 70 (55%) were female, 71 (56%) were PS-0 and 51 (40%) had primary in situ tumor. Fifty-three (41%) patients entered Phase-B. The median baseline (b) NLR was 3.2 (range: 1.5–20.4) with 32 (25%) patients having bNLR > 5. The PFS hazard ratio (HR) by bNLR > 5 versus ≤ 5 was 1.4 (95% CI: 0.9–2.2; p = 0.101). The median PFS was 9.2 months (95% CI: 7.9–10.8) for Phase-A and 6.7 months (95% CI: 3.0–8.2) for Phase-B. The HR for OS based on bNLR > 5 versus ≤ 5 was 1.6 (95% CI: 1.0–2.7; p = 0.052). The median OS was 25 months (95% CI: 19.2–29.7) for the full analysis set and 14.9 months for Phase-B. Baseline levels of nine proteomic markers showed a relationship with PFS. Treatment related toxicities were consistent with what has previously been published. There were 4 (3%) instances of GI perforation, of which, 3 (6%) occurred in the primary in situ tumor group. Conclusions: Results from this study are aligned with the previously reported trend towards worse PFS and OS in patients with higher bNLR. Trial registration: ClinicalTrials.gov: NCT01588990; posted May 1, 2012. [ABSTRACT FROM AUTHOR]

Aims: Inflammation is a hallmark of cancer whose activity is modulated within the tumor microenvironment by low tumoral pH. Recent evidence in the literature has suggested a link between low serum bicarbonate, low tumoral pH and cancer related inflammation. There is however little clinical evidence in human patients regarding the prognostic role of serum bicarbonate. Therefore, the primary aim of this study was to investigate the short and long-term prognostic utility of serum bicarbonate in colorectal cancer (CRC) patients undergoing resection of their primary tumor. The study also aimed to investigate the association of serum bicarbonate with known markers of systemic inflammation. Methods: A total of 3281 consecutive patients who underwent surgical resection of their primary CRC from January 1998 to December 2012. Of these, 2223 stage I-IV patients had available data for analysis. The association of serum bicarbonate with overall survival was assessed using univariate and multivariate cox regression analyses. The association of bicarbonate with other clinicopathological variables was assessed by chi squared and Fisher's exact tests. Results: Serum bicarbonate was associated with peri-operative mortality in multivariate analysis (p<0.001). Age (p = 0.004), grade (p = 0.043), creatinine (p = 0.036) and sodium (p = 0.036) were also markers associated with peri-operative mortality. For long term survival at 5 years, bicarbonate was significantly associated with overall survival in univariate analysis (p<0.001) but was not significant in multivariate analysis (p = 0.075). In exploratory analysis, serum bicarbonate was found to be significantly associated with the lymphocyte-to-monocyte ratio (p<0.001) and neutrophil-to-lymphocyte ratio (p<0.001). Conclusions: In peri-operative colorectal cancer patients, serum bicarbonate was associated with 30-day survival but not 5-year survival. [ABSTRACT FROM AUTHOR]

Background: Recent literature has suggested that tumor sidedness in colorectal cancer (CRC) is an independent prognostic and potentially predictive marker of survival. The aims of the study were to determine the prognostic significance of tumor sidedness in colorectal cancer patients undergoing primary tumor resection and to assess associated tumor biology. Methods: A total of 3281 consecutive patients who underwent surgical resection of their primary CRC from January 1998 to December 2012 were analyzed for association with tumor biologic factors and with overall survival. Metastatic patients were excluded from analysis. Results: Left sided CRCs were associated with a number of additional key prognostic markers including BRAFV600E wildtype status (P<0.001), mismatch repair proficiency (p<0.001), absence of peritumoral lymphocytic response (p = 0.001), high lymphocyte-to-monocyte ratio (p<0.001) and low neutrophil-to-lymphocyte ratio (p<0.001). In primary analysis with 3067 patients, there was no statistical difference in sidedness in the univariate analysis (p = 0.291). Three further subgroup analyses were performed. In the first subgroup, only stage III patients were analyzed. In the second, patients with mismatch repair deficiency were removed. In the third, additional clinicopathologic variables known to be independently prognostic were added into analysis. In all three subgroup analyses tumor sidedness was not an independent prognostic marker. Conclusions: Tumor sidedness was not an independent prognostic marker of CRC. However, right sided CRCs were associated with several key independent prognostic markers supporting a hypothesis that tumor sidedness is a surrogate for other biomarkers. [ABSTRACT FROM AUTHOR]