title: Systemic inflammatory response predicts prognosis in patients with advanced-stage colorectal cancer.
abstract: We aim to confirm the prognostic value of an inflammation-based prognostic score (the Glasgow Prognostic Score [GPS]) in advanced colorectal cancer, to explore a predictive pattern of plasma cytokines and their gene polymorphisms for clinical outcome, and to investigate which cytokines contribute to GPS. Inflammatory markers were measured at baseline in 52 patients with stage IV colorectal cancer. Germline DNA was genotyped for interleukin (IL)-1beta-511, IL-1beta +3954, IL-6-174, TNF-alpha-308, IL-10-1082, and IL-10 -592 using Sequenome mass spectrometry-based genotyping technology. Toxicity was graded by the National Cancer Institute Common Toxicity Criteria version 2.0. Response was assessed by the Response Evaluation Criteria in Solid Tumors. Glasgow Prognostic Score, carcinoembryonic antigen and hypoalbuminemia were predictive of overall survival (OS). Hypoalbuminemia (< or = 35 g/L) and GPS were predictive of toxicity; GPS 2 was predictive of increased grade 2/3 toxicity compared with patients with a GPS of 0 or 1 (P < .05). Interleukin-10-592AA and IL-10 -1082CC predicted for OS (P < .05). Elevated levels of circulating IL-4 and soluble glycoprotein 130 (sgp130) were associated with increased grade 2/3 toxicity. Significantly elevated levels of IL-6 and sgp130 were observed in patients with a GPS of 2 (P < .05). In this patient group, inflammatory markers predict for clinical outcome. This could improve prognostication and allow for intervention strategies to reduce tumor-associated inflammation.
authors.affiliation: Ovarian Cancer Action (HHMT) Research Unit, Imperial College, London, United Kingdom.
authors.forename: Rohini
authors.initials: R
authors.lastname: Sharma
authors.forename: Manuela
authors.initials: M
authors.lastname: Zucknick
authors.forename: Roslyn
authors.initials: R
authors.lastname: London
authors.forename: Marina
authors.initials: M
authors.lastname: Kacevska
authors.forename: Christopher
authors.initials: C
authors.lastname: Liddle
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Clarke
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000097:blood / Q000235:genetics / Q000401:mortality*; D016207:Cytokines / Q000097:blood / Q000235:genetics; D005260:Female; D006305:Health Status Indicators; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D015996:Survival Rate; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines