Systemic inflammation score predicts survival in patients with intrahepatic cholangiocarcinoma undergoing curative resection

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Abstract

Inflammation has a critical role in the development and progression of cancers. We developed a novel systemic inflammation score (SIS) based on lymphocyte, monocyte, and CA19-9 and explored its prognostic value in intrahepatic cholangiocarcinoma (ICC). From January 2005 to December 2011, 322 consecutive ICC patients who underwent curative resection in our center were included in this study, and validated in a retrospective study of 126 patients enrolled from 2012 to 2014. Clinicopathological variables including preoperative serum CA19-9 and LMR were analyzed. The cutoff values of CA19-9 and LMR were determined based on receiver operating characteristics curve analysis in the primary cohort. Kaplan-Meier curves and multivariate Cox-regression analyses were calculated for time to recurrence (TTR) and overall survival (OS). In univariate analysis of all patients, all three inflammatory and tumor marker including NLR ≥ 2.49 ( P<0.001), LMR ≤ 4.45 ( P=0.002), and CA19-9≥89 ( P<0.001) were associated with poor prognoses. When omitting SIS in multivariate analysis, preoperative LMR ( P =0.006) and serum CA19-9 ( P<0.001) were independent predictors of OS. In addition, elevated CA19-9 ( P=0.001), multiple tumors ( P<0.001), and lymph node metastasis ( P<0.001) were significant predictors of worse recurrence free survival. Moreover, high SIS was significantly associated with aggressive tumor behaviours including large tumor size ( P<0.001), multiple tumors ( P=0.033), lymphonodus node metastasis ( P=0.001), and high TNM stage ( P<0.0001). Finally, univariate and multivariate analyses revealed the SIS was an independent predictor for TTR (HR=2.077, 95% CI, 1.365-3.162, P=0.001) and OS (HR=3.133 95% CI, 2.058-4.769, P<0.001). These results were further confirmed in the validation cohort. In conclusions, our findings demonstrate that the SIS as a potentially powerful prognostic biomarker in ICC that predicts poor clinical outcomes and is a promising tool for ICC treatment strategy decisions.

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Most cited references 34

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Lymphopenia as a prognostic factor for overall survival in advanced carcinomas, sarcomas, and lymphomas.

Isabelle Ray-Coquard, Claire Cropet, Martine Van Glabbeke … (2009)

Lymphopenia is frequent in advanced cancers and predicts the toxicity of chemotherapy. Its effect on relapse and survival is uncertain. Its prognostic value for survival was analyzed in three databases of previously reported prospective multicenter studies: (a) FEC chemotherapy in metastatic breast carcinoma; (b) CYVADIC in advanced soft tissue sarcoma (European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group 62791); and (c) prospective, consecutive phase III studies of aggressive diffuse large-cell non-Hodgkin's lymphomas conducted at Centre Léon Bérard between 1987 and 1993. Univariate and multivariate analyses of prognostic factors for survival were performed. The incidence of lymphopenia of 1, non-Hodgkin's lymphoma patients with international prognostic index (IPI) of > 0, and advanced soft tissue sarcoma and metastatic breast cancer patients with bone metastases. Inunivariate analysis, lymphopenia of <1,000/microL significantly correlated to overall survival in patients with metastatic breast cancer (median, 10 versus 14 mo; P < 0.0001), advanced soft tissue sarcoma (median, 5 versus 10 months; P < 0.01), and non-Hodgkin lymphoma (median, 11 versus 94 months; P < 0.0001). In multivariate analysis (Cox model), lymphopenia was an independent prognostic factor for overall survival in metastatic breast cancer [RR (relative risk), 1.8; 95% CI (confidence interval), 1.3-2.4] along with liver metastases and PS; in advanced soft tissue sarcoma (RR, 1.46; 95% CI, 1.0-2.1) along with liver metastases, lung metastases, and PS; and in non-Hodgkin's lymphoma (RR, 1.48; 95% CI, 1.03-2.1) along with IPI. Our findings show that lymphopenia is an independent prognostic factor for overall and progression-free survival in several cancers.

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Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States.

T. Patel (2001)

Clinical observations suggest a recent increase in intrahepatic biliary tract malignancies. Thus, our aim was to determine recent trends in the epidemiology of intrahepatic cholangiocarcinoma in the United States. Reported data from the Surveillance, Epidemiology, and End Results (SEER) program and the United States Vital Statistics databases were analyzed to determine the incidence, mortality, and survival rates of primary intrahepatic cholangiocarcinoma. Between 1973 and 1997, the incidence and mortality rates from intrahepatic cholangiocarcinoma markedly increased, with an estimated annual percent change (EAPC) of 9.11% (95% CI, 7.46 to 10.78) and 9.44% (95%, CI 8.46 to 10.41), respectively. The age-adjusted mortality rate per 100,000 persons for whites increased from 0.14 for the period 1975-1979 to 0.65 for the period 1993-1997, and that for blacks increased from 0.15 to 0.58 over the same period. The increase in mortality was similar across all age groups above age 45. The relative 1- and 2-year survival rates following diagnosis from 1989 to 1996 were 24.5% and 12.8%, respectively. In conclusion, there has been a marked increase in the incidence and mortality from intrahepatic cholangiocarcinoma in the United States in recent years. This tumor continues to be associated with a poor prognosis.

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An inflammation-based prognostic score (mGPS) predicts cancer survival independent of tumour site: a Glasgow Inflammation Outcome Study

M J Proctor, D Morrison, D Talwar … (2011)

Introduction: A selective combination of C-reactive protein and albumin (termed the modified Glasgow Prognostic Score, mGPS) has been shown to have prognostic value, independent of tumour stage, in lung, gastrointestinal and renal cancers. It is also of interest that liver function tests such as bilirubin, alkaline phosphatase and γ-glutamyl transferase, as well as serum calcium, have also been reported to predict cancer survival. The aim of the present study was to examine the relationship between an inflammation-based prognostic score (mGPS), biochemical parameters, tumour site and survival in a large cohort of patients with cancer. Methods: Patients (n=21 669) who had an incidental blood sample taken between 2000 and 2006 for C-reactive protein, albumin and calcium (and liver function tests where available) and a diagnosis of cancer were identified. Of this group 9608 patients who had an ongoing malignant process were studied (sampled within 2 years before diagnosis). Also a subgroup of 5397 sampled at the time of diagnosis (sampled within 2 months prior to diagnosis) were examined. Cancers were grouped by tumour site in accordance with International Classification of Diseases 10 (ICD 10). Results: On follow up, there were 6005 (63%) deaths of which 5122 (53%) were cancer deaths. The median time from blood sampling to diagnosis was 1.4 months. Increasing age, male gender and increasing deprivation was associated with a reduced 5-year overall and cancer-specific survival (all P<0.001). An elevated mGPS, adjusted calcium, bilirubin, alkaline phosphatase, aspartate transaminase, alanine transaminase and γ-glutamyl transferase were associated with a reduced 5-year overall and cancer-specific survival (independent of age, sex and deprivation in all patients sampled), as well as within the time of diagnosis subgroup (all P<0.001). An increasing mGPS was predictive of a reduced cancer-specific survival in all cancers (all P<0.001). Conclusion: The results of the present study indicate that the mGPS is a powerful prognostic factor when compared with other biochemical parameters and independent of tumour site in patients with cancer.

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Author and article information

Journal

Journal ID (nlm-ta): J Cancer

Journal ID (iso-abbrev): J Cancer

Journal ID (publisher-id): jca

Title: Journal of Cancer

Publisher: Ivyspring International Publisher (Sydney )

ISSN (Electronic): 1837-9664

Publication date Collection: 2019

Publication date (Electronic): 1 January 2019

Volume: 10

Issue: 2

Pages: 494-503

Affiliations

[1 ]Department of General Surgery, Zhongshan Hospital (South), Fudan University, Shanghai Public Health Clinical Center, Fudan University, Shanghai 200083, China

[2 ]Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, China

[3 ]Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China

[4 ]Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China

[5 ]Cancer Research Institute, Central South University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha 410078, China

[6 ]State key laboratory of genetic engineering, Fudan University, Shanghai 200032, China.

Author notes

✉ Corresponding authors: Qing Chen, Department of General Surgery, Zhongshan Hospital (South), Fudan University; Shanghai Public Health Clinical Center, Fudan University, 921 Tongxin Road, Shanghai 200083, China. Phone: +86-21-37990333, E-mail: chenqing_84@ 123456163.com ; or Jian Zhou, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai 200032, China. Phone: +86-21-64041990; Fax: +86-21-64037181, E-mail: zhou.jian@ 123456zs-hospital.sh.cn .

†These authors contributed equally to this work.

Competing Interests: The authors have declared that no competing interest exists.

Article

Publisher ID: jcav10p0494

DOI: 10.7150/jca.26890

PMC ID: 6360305

PubMed ID: 30719145

SO-VID: bec4dce3-9e8f-4d72-9886-c12401540817

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This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.

Systemic inflammation score predicts survival in patients with intrahepatic cholangiocarcinoma undergoing curative resection

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Most cited references 34

Lymphopenia as a prognostic factor for overall survival in advanced carcinomas, sarcomas, and lymphomas.

Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States.

An inflammation-based prognostic score (mGPS) predicts cancer survival independent of tumour site: a Glasgow Inflammation Outcome Study

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