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PROGNOSTIC SIGNIFICANCE OF LYMPHOCYTE-C-REACTIVE PROTEIN RATIO IN PATIENTS WITH PRIMARY LIVER CANCER
Abdullah Altaf
*1, Mujtaba Khalil
1, Miho Akabane
1, Zayed Rashid
1, Jun Kawashima
1, Shahzaib Zindani
1, Azza Sarfraz
1, Andrea Ruzzenente
2, Luca Aldrighetti
3, Todd W. Bauer
4, Hugo P. Marques
5, Guillaume Martel
6, Irinel Popescu
7, Matthew Weiss
8, Minoru Kitago
9, George A. Poultsides
10, Shishir K. Maithel
11, Carlo Pulitano
12, Vincent Lam
13, Ana Gleisner
14, Tom Hugh
15, Feng Shen
16, François Cauchy
17, B. Groot Koerkamp
18, Itaru Endo
19, Timothy M. Pawlik
11The Ohio State University Wexner Medical Center, Columbus, OH; 2Universita degli Studi di Verona, Verona, Veneto, Italy; 3IRCCS Ospedale San Raffaele, Milano, Italy; 4University of Virginia School of Medicine, Charlottesville, VA; 5Hospital Curry Cabral, Lisboa, Lisboa, Portugal; 6University of Ottawa, Ottawa, ON, Canada; 7Institutul Clinic Fundeni, Bucuresti, Romania; 8Northwell Health, New Hyde Park, NY; 9Keio Gijuku Daigaku Byoin, Shinjuku-ku, Tokyo, Japan; 10Stanford University School of Medicine, Stanford, CA; 11Emory University, Atlanta, GA; 12Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia; 13Westmead Hospital, Westmead, New South Wales, Australia; 14University of Colorado System, Denver, CO; 15The University of Sydney, Sydney, New South Wales, Australia; 16Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China; 17Hopital Beaujon, Clichy, Île-de-France, France; 18Erasmus MC, Rotterdam, Zuid-Holland, Netherlands; 19Yokohama Shiritsu Daigaku Igakubu Daigakuin Igaku Kenkyuka, Yokohama, Kanagawa, Japan
Background: Systemic inflammation due to host-tumor interactions, as well as host immune response play a significant role in the progression of cancer. We sought to characterize the prognostic value of lymphocyte-C-reactive protein ratio (LCR) versus other inflammatory markers to predict short- and long-term outcomes among patients undergoing liver resection (LR) for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).
Methods: Patients who underwent curative-intent LR for HCC and ICC between 2000-2023 were identified from an international, multi-institutional database. We evaluated the prognostic value of different combinations of preoperative C-reactive protein (CRP), serum albumin, neutrophil, lymphocyte and platelet count relative to short- (i.e., postoperative morbidity) and long-term (recurrence-free survival [RFS] and overall survival [OS]) outcomes.
Results: Among 715 patients in the analytic cohort, 499 (69.8%) and 216 (30.2%) individuals were included in the derivation and validation cohorts, respectively. On receiver operating characteristic (ROC) curve analysis in the derivation cohort, LCR demonstrated the highest accuracy among the inflammatory markers to predict RFS and OS, with areas under the ROC curve (AUC) of 0.724 (95%CI: 0.675-0.768) and 0.716 (95%CI: 0.662-0.769), respectively (
Table 1). An optimal LCR cut-off threshold of 6,100 was identified. Patients with poorly or undifferentiated tumors (poorly/undifferentiated: 5,993.3 vs. well/moderately differentiated: 9,032.6), perineural invasion (3,961.5 vs. 8,157.8), major vascular invasion (2,694.0 vs. 7,390.0), advanced T stage (T3/T4: 2575.1 vs. T1/T2: 8,157.8), and lymph node metastasis (N1/Nx: 4,929.8 vs. N0: 8,531.3) had lower median levels of LCR (all p-values <0.05). After adjusting for relevant clinicodemographic factors on logistic regression, lower LCR was associated with higher incidence of postoperative complications (OR: 1.98 [95%CI: 1.27-3.10]; p=0.003), and particularly postoperative infectious complications (OR: 2.80 [95%CI: 1.57-5.01]; p<0.001). In addition, a lower LCR was independently associated with worse RFS (HR: 2.43 [95%CI: 1.41-3.83]; p=0.002) and OS (HR: 2.95 [95%CI: 2.10-4.16]; p<0.001) on Cox regression analysis. The prognostic ability of LCR for short- and long-term outcomes performed well in an independent validation cohort.
Conclusion: As an inflammatory biomarker, LCR was strongly associated with risk of postoperative morbidity, as well as recurrence and worse long-term survival among patients undergoing LR for HCC and ICC. Preoperative LCR assessment can aid surgeons in the preoperative risk-stratification of patients undergoing surgery for primary liver cancer.
Table 1. ROC curve analysis for recurrence-free and overall survival in the derivation cohort.
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