C. T. Aquina1, A. S. Rickles1, C. P. Probst1, B. J. Hensley1, A. A. Swanger1, K. Noyes1, J. R. Monson1, F. Fleming1 1University Of Rochester,Surgical Health Outcomes & Research Enterprise (S.H.O.R.E.),Rochester, NY, USA
Introduction: Much recent attention has been directed towards the detrimental effects of a pro-inflammatory state on tumorigenesis and oncologic outcomes. Our research group has previously shown a relationship between elevated metabolically active visceral fat volume and recurrence-free survival in colorectal cancer. Other studies have demonstrated a similar link to colorectal cancer outcomes with laboratory inflammation markers such as the neutrophil-to-lymphocyte ratio. We sought to investigate whether pre-operative inflammatory indices are associated with long-term colorectal cancer outcomes and whether this relationship is mediated by visceral obesity.
Methods: A single-center retrospective chart review was performed for patients undergoing surgical resection for colorectal cancer between 2000 and 2009. Pre-operative CT scans were used to calculate visceral fat volume (VFV) based upon a previously validated method. Pre-operative laboratory values within 90 days of the date of surgery were used to calculate the neutrophil-to-lymphocyte ratio (NLR). A pre-operative NLR>3 was used as a cut-off to define high NLR according to previous literature. Visceral obesity was defined as VFV>1620cm3 based upon the results of a receiver operating characteristic curve. Five-year recurrence-free survival was defined as locoregional or distant recurrence within 5 years of surgery. Chi-square, Student’s T-test, Kaplan-Meier, and Cox proportional-hazards analysis were used to compare pre-operative and surgical characteristics with recurrence-free survival.
Results: Overall, 141 patients met inclusion criteria with 75 patients having a high NLR (53.2%) and 48 patients having visceral obesity (34%). Patients with a high NLR had significantly higher levels of VFV (mean=1741cm3 vs. 1399cm3, p=0.04). On Kaplan-Meier analysis, both high NLR (p=0.03) and visceral obesity (p=0.005) were independently associated with reduced 5-year recurrence-free survival for stage II colorectal cancer but not stages I or III. Using separate Cox proportional-hazards models due to the association between high NLR and visceral obesity, both high NLR (HR=4.04, p=0.04) and visceral obesity (HR=4.05, p=0.03) were associated with a more than 4-fold risk of cancer recurrence within 5 years for stage II colorectal cancer.
Conclusion: Both pre-operative systemic inflammation, as captured by an elevated pre-operative neutrophil-to-lymphocyte ratio, and visceral obesity are associated with worse recurrence-free survival for stage II colorectal cancer. Additional study is warranted at exploring the association between these two factors and developing strategies at improving outcomes for this high-risk population.