S. Buettner2, B. Groot Koerkamp2, M. Weiss3, S. Alexandrescu4, H. P. Marques5, J. Lamelas5, L. Aldrighetti6, T. Gamblin7, S. K. Maithel8, C. Pulitano9, T. W. Bauer10, F. Shen11, G. A. Poultsides12, J. Marsh13, J. N. IJzermans2, T. M. Pawlik1 1Ohio State University,Columbus, OH, USA 2Erasmus MC University Medical Center,Dept. Of Surgery,Rotterdam, ZUID-HOLLAND, Netherlands 3Johns Hopkins University School Of Medicine,Baltimore, MD, USA 4Fundeni Clinical Institute,Bucharest, ROMANIA, Romania 5Curry Cabral Hospital,Lisbon, PORTUGAL, Portugal 6Ospedale San Raffaele,Milan, ITALY, Italy 7Medical College Of Wisconsin,Milwaukee, WI, USA 8Emory University School Of Medicine,Atlanta, GA, USA 9University Of Sydney,Sydney, NSW, Australia 10University Of Virginia,Charlottesville, VA, USA 11Eastern Hepatobiliary Surgery Hospital,Shanghai, CHINA, China 12Stanford University,Palo Alto, CA, USA 13University Of Pittsburg,Pittsburgh, PA, USA
Introduction: Alterations in the Neutrophil-to-Lymphocyte ratio (NLR) may be indicative of host immune response to cancer. We sought to determine whether preoperative NLR was associated with long-term outcomes among patients undergoing surgery for intrahepatic cholangiocarcinoma (ICC).
Methods: Patients who underwent resection for ICC between 1990-2015 were identified from 12 major HPB centers. NLR was calculated by dividing the absolute number of neutrophils by the absolute number of lymphocytes. The Kaplan-Meier method and Cox regression models were used to evaluate factors, including NLR, that potentially were associated with overall survival. Factors associated with survival based on the multivariable Cox model were utilized to create a point-based preoperative score to predict prognosis.
Results: Among 1,000 patients who underwent resection for ICC, the majority of patients had a solitary tumor (n=810, 82.6%) and median tumor size was 6.0 cm (interquartile range [IQR]: 4.3-9.0); 168 (19.5%) patients had lymph node metastases on preoperative imaging. Preoperative jaundice was present in 98 (9.8%) patients, while 27 (2.7%) patients had extrahepatic disease. Median NLR was 2.68 (2.05-4.00). Overall survival at 1-, 3-, and 5- years was 78.7%, 61.5%, and 39.1%, respectively. NLR was associated with prognosis as patients with a NLR ≥3 had a median survival of 31.3 months (95%CI: 23.9-38.8) compared with 53.1 months (95%CI: 37.1-69.2) among patients with a lower NLR (p<0.001). In addition, 1-, 3-, and 5-year survival was 73.5%, 46.4%, and 38.8% versus 84.6%, 61.1%, and 47.8% among patients with NLR ≥3 versus NLR < 3, respectively (p<0.001). Using backwards selection based on the Akaike Information Criterion, a preoperative risk score was derived. Specifically, on multivariable analysis, number of lesions (Hazard Ratio [HR]: 1.17; p<0.001), tumor size (HR: 1.04; p<0.001), preoperative lymph node metastases (HR: 1.32; p=0.022), preoperative jaundice (HR: 1.65; p<0.001) and extrahepatic disease (HR: 2.39, p<0.001) were each predictive of survival. After controlling for these competing risk factors, NLR remained independently associated with long-term survival (HR: 1.04, 95%CI: 1.02-1.07; p=0.001). The combination of these preoperative factors into a prognostic model had fair discrimination to predict post-operative survival (area under the curve, 0.65).
Conclusion: Elevated NLR was an independent predictor of worse long-term outcomes among patients with ICC undergoing resection. NLR may be an important factor associated with survival and can help estimate postoperative survival when used in a preoperative predictive model.
