British Journal of Cancer · 2011 · 473 citations · 28 references
MedicineImmunologyOncologyChemotherapyMedical OncologyPalliative OncologyCancer BiomarkersCancer Survival AnalysisColorectal CancerImmuno-oncology BiomarkersToxicity GradingBaseline Laboratory TestingChemotherapy Response AssessmentColorectal Cancer BiomarkersColorectal Cancer PrognosisImmune MarkersNeutrophil-to-lymphocyte RatioPrognostic VariablesSingle-agent Chemotherapy
BACKGROUND: Advances in the treatment of metastatic colorectal cancer (mCRC) in the last decade have significantly improved survival; however, simple biomarkers to predict response or toxicity have not been identified, which are applicable to all community oncology settings worldwide. The use of inflammatory markers based on differential white-cell counts, such as the neutrophil/lymphocyte ratio (NLR), may be simple and readily available biomarkers. METHODS: Clinical information and baseline laboratory parameters were available for 349 patients, from two independent cohorts, with unresectable mCRC receiving first-line palliative chemotherapy. Associations between baseline prognostic variables, including inflammatory markers such as the NLR and tumour response, progression and survival were investigated. RESULTS: In the training cohort, combination-agent chemotherapy (P=0.001) and NLR ≤ 5 (P=0.003) were associated with improved clinical benefit. The ECOG performance status 1 (P=0.002), NLR>5 (P=0.01), hypoalbuminaemia (P=0.03) and single-agent chemotherapy (P<0.0001) were associated with increased risk of progression. The ECOG performance status ≥ 1 (P=0.004) and NLR>5 (P=0.002) predicted worse overall survival (OS). The NLR was confirmed to independently predict OS in the validation cohort (P<0.0001). Normalisation of the NLR after one cycle of chemotherapy in a subset of patients resulted in improved progression-free survival (P=0.012). CONCLUSION: These results have highlighted NLR as a potentially useful clinical biomarker of systemic inflammatory response in predicting clinically meaningful outcomes in two independent cohorts. Results of this study have also confirmed the importance of a chronic systemic inflammatory response influencing clinical outcomes in patients with mCRC.
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