Association of Systemic Inflammation and Sarcopenia With Survival in Nonmetastatic Colorectal Cancer

Abstract

<h3>Importance</h3> Systemic inflammation and sarcopenia are easily evaluated, predict mortality in many cancers, and are potentially modifiable. The combination of inflammation and sarcopenia may be able to identify patients with early-stage colorectal cancer (CRC) with poor prognosis. <h3>Objective</h3> To examine associations of prediagnostic systemic inflammation with at-diagnosis sarcopenia, and determine whether these factors interact to predict CRC survival, adjusting for age, ethnicity, sex, body mass index, stage, and cancer site. <h3>Design, Setting, and Participants</h3> A prospective cohort of 2470 Kaiser Permanente patients with stage I to III CRC diagnosed from 2006 through 2011. <h3>Exposures</h3> Our primary measure of inflammation was the neutrophil to lymphocyte ratio (NLR). We averaged NLR in the 24 months before diagnosis (mean count = 3 measures; mean time before diagnosis = 7 mo). The reference group was NLR of less than 3, indicating low or no inflammation. <h3>Main Outcomes and Measures</h3> Using computed tomography scans, we calculated skeletal muscle index (muscle area at the third lumbar vertebra divided by squared height). Sarcopenia was defined as less than 52 cm²/m²and less than 38 cm²/m²for normal or overweight men and women, respectively, and less than 54 cm²/m²and less than 47 cm²/m²for obese men and women, respectively. The main outcome was death (overall or CRC related). <h3>Results</h3> Among 2470 patients, 1219 (49%) were female; mean (SD) age was 63 (12) years. An NLR of 3 or greater and sarcopenia were common (1133 [46%] and 1078 [44%], respectively). Over a median of 6 years of follow-up, we observed 656 deaths, 357 from CRC. Increasing NLR was associated with sarcopenia in a dose-response manner (compared with NLR &lt; 3, odds ratio, 1.35; 95% CI, 1.10-1.67 for NLR 3 to &lt;5; 1.47; 95% CI, 1.16-1.85 for NLR ≥ 5;<i>P</i>for trend &lt; .001). An NLR of 3 or greater and sarcopenia independently predicted overall (hazard ratio [HR], 1.64; 95% CI, 1.40-1.91 and HR, 1.28; 95% CI, 1.10-1.53, respectively) and CRC-related death (HR, 1.71; 95% CI, 1.39-2.12 and HR, 1.42; 95% CI, 1.13-1.78, respectively). Patients with both sarcopenia and NLR of 3 or greater (vs neither) had double the risk of death, overall (HR, 2.12; 95% CI, 1.70-2.65) and CRC related (HR, 2.43; 95% CI, 1.79-3.29). <h3>Conclusions and Relevance</h3> Prediagnosis inflammation was associated with at-diagnosis sarcopenia. Sarcopenia combined with inflammation nearly doubled risk of death, suggesting that these commonly collected biomarkers could enhance prognostication. A better understanding of how the host inflammatory/immune response influences changes in skeletal muscle may open new therapeutic avenues to improve cancer outcomes.