Abstract 2250: Systemic inflammation and sarcopenia predict colorectal cancer survival
Authors: Feliciano Elizabeth M. Cespedes , Kroenke Candyce H. , Meyerhardt Jeffrey , Prado Carla M. , Bradshaw Patrick T. , Kwan Marilyn , Xiao Jingjie , Alexeef Stacey , Weltzien Erin K. , Castillo Adriemme L. , Caan Bette J. 
Published: July 2017

Importance: A higher neutrophil-to-lymphocyte ratio (NLR, indicating systemic inflammation), and sarcopenia (reduced skeletal muscle mass) predict morbidity/mortality in a variety of cancers, but no prior research examines associations of pre-diagnostic NLR with at-diagnosis sarcopenia, nor whether NLR and sarcopenia combined identify early-stage patients with poor prognosis in colorectal cancer (CRC).Objective: To evaluate the association between pre-diagnosis NLR and at-diagnosis sarcopenia and of their combination with CRC survival, controlling for age, ethnicity, sex, body mass index, stage, and cancer site.

Design, Setting, and Participants: This observational cohort with prospectively-collected data included 2470 patients diagnosed with stage I-III CRC at Kaiser Permanente from 2006-2011 with computed tomography (CT) scans from clinical care (mean days pre-diagnosis=6).

Exposures: Systemic inflammation measured via average NLR in the 24 months pre-diagnosis (mean count=3 measures, mean months pre-diagnosis=7). The reference value was NLR below 3, indicating low/no inflammation.

Main Outcomes and Measures: Sarcopenia, defined by published cutoffs for skeletal muscle index (CT muscle area in cm2 at the third lumbar vertebra divided by squared height in m2; below 52-cm2/m2 and 38-cm2/m2 for normal/overweight men and women, respectively, and below 54-cm2/m2 and 47-cm2/m2 for obese men and women, respectively), and incident death (overall or CRC-related).

Results: Average age was 63 years; half of patients were female. NLR above 3 and sarcopenia were common (46% and 44%, respectively). Over a median of 6 years, we observed 656 deaths, 357 from CRC. Elevated NLR was associated with sarcopenia in a dose-response manner (compared to NLR below 3, Odds Ratio [OR]=1.35; 95%CI:1.10-1.67 for NLR 3-5; OR=1.47; 95%CI:1.16-1.85 for NLR above 5). NLR above 3 and sarcopenia were also independently associated with survival (Hazard Ratio [HR]=1.65; 95%CI:1.45-1.98 for overall death and HR=1.29; 95%CI:1.09-1.53 for CRC death); patients with both sarcopenia and NLR above 3 (versus neither), had double the risk of death overall (HR=2.53; 95%CI:1.87-3.41) and from CRC (HR=2.19; 95%CI:1.74-2.75).

Conclusions and Relevance: Host inflammatory/immune response shortly prior to diagnosis predicts muscularity at diagnosis. Low muscle combined with systemic inflammation predicts worse CRC prognosis regardless of stage. A better understanding of the crosstalk between inflammatory/immune responses and the onset of changes in skeletal muscle may open new therapeutic avenues to improve cancer outcomes.

Citation Format: Elizabeth M. Cespedes Feliciano, Candyce H. Kroenke, Jeffrey Meyerhardt, Carla M. Prado, Patrick T. Bradshaw, Marilyn Kwan, Jingjie Xiao, Stacey Alexeef, Erin K. Weltzien, Adriemme L. Castillo, Bette J. Caan. Systemic inflammation and sarcopenia predict colorectal cancer survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2250. doi:10.1158/1538-7445.AM2017-2250