The inflammatory index neutrophil/lymphocyte ratio (NLR) has an adverse prognostic value in patients with localized colorectal cancer (CRC). We aimed at evaluating its role in metastatic CRC (mCRC) patients treated with standard first-line chemotherapy. Among consecutive CRC patients referred to our Unit, those with metastatic disease eligible for treatment with fluorouracil, irinotecan and bevacizumab (FOLFIRI-Bev) were included in the study. NLR was routinely assessed before each treatment cycle and correlated with outcome together with common clinical, biochemical and histological variables. A sub-analysis focused on patients with stable disease (SD) was also performed to test the net influence of NLR changes independently of tumor shrinkage. At multivariate Cox regression analysis, baseline NLR, taken as continuous variable, was the most powerful prognosticator for survival (HR 1.80, p 0.0019). Surprisingly, among SD patients, the prognostic effect of NLR changes after two cycles of therapy was of opposite sign, and those in whom NLR increased or was maintained had a 67 % reduction in the risk of death as compared with patients with significant NLR decrease: mOS 56 versus 23 months, respectively, p 0.02. In conclusion, we were able to confirm the adverse prognostic value of high baseline NLR for mCRC patients treated with FOLFIRI-Bev. However, FOLFIRI-Bev-induced NLR changes in SD patients seem to differently affect survival. The specific molecular pathways involved in NLR modulation by FOLFIRI-Bev warrant further investigation.

Excision repair cross-complementation group 1 (ERCC1) is a key component in DNA repair mechanisms and may influence the tumor DNA-targeting effect of the chemotherapeutic agent oxaliplatin. Germline ERCC1 polymorphisms may alter the protein expression and published data on their predictive and prognostic value have so far been contradictory. In the present article we review available evidence on the clinical role and utility of ERCC1 polymorphisms and, in the absence of a 'perfect' trial, what we call the 'sliding doors' trial, we present the data of ERCC1 genotyping in our local patient population. We found a useful predictive value for oxaliplatin-induced risk of anemia.

Among the possible genetic contributors to cancer-related venous thromboembolism (VTE), vascular endothelial growth factor (VEGFA) could play an important role, as an imbalance of the VEGFA system (either disease-related or drug-induced) may result in a disturbance of vascular homeostasis. Thus, this study was designed to investigate the predictive role of eight different VEGFA gene promoter single nucleotide polymorphisms (SNPs) for a first VTE episode in cancer out-patients undergoing chemotherapy. To this purpose, VEGFA gene promoter polymorphisms were analysed in 297 cancer patients using polymerase chain reaction amplification and direct DNA sequencing analysis. One hundred forty unrelated healthy subjects from the same geographical area were also analysed in order to evaluate and compare genotype/haplotype frequencies in our ethnicity. VTE occurred in 26 (9%) of cancer patients with a median time-to-event of 3.4 months. Association analyses showed that -1154G/A polymorphism was significantly associated with the risk of chemotherapy-triggered VTE, with the A allele exerting a protective role both in the overall population (hazard ratio [HR]: 0.21; 95% confidence interval [CI]: 0.07-0.58) or in bevacizumab-treated metastatic patients (HR: 0.09, 95%CI: 0.01-0.86) in whom VEGFA -1154AA genotype also conferred a reduced risk of early progression (HR: 0.58, 95%CI: 0.34-0.98). These results suggest that VEGFA may represent a candidate gene contributing to VTE development in chemotherapy treated cancer patients and that -1154G/A SNP might provide useful clinical information on the efficacy and toxicity of bevacizumab in metastatic patients. Validation studies are needed for translation into clinical practice.

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High Neutrophil/Lymphocyte ratio (NLR), as a measure of enhanced inflammatory response, has been negatively associated with prognosis in patients with localized pancreatic ductal adenocarcinoma (PDA)