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Wei YC, Yun L, Liang YL, Grimm R, Yang C, Tao YF, Jiang SC, Liao JY. Nomogram based on the neutrophil-to-lymphocyte ratio and MR diffusion quantitative parameters for predicting Ki67 expression in hepatocellular carcinoma from a prospective study. Sci Rep 2024; 14:31738. [PMID: 39738357 PMCID: PMC11685758 DOI: 10.1038/s41598-024-82333-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Accepted: 12/04/2024] [Indexed: 01/02/2025] Open
Abstract
This study aimed to establish and validate a multiparameter prediction model for Ki67 expression in hepatocellular carcinoma (HCC) patients while also exploring its potential to predict the one-year recurrence risk. The clinical, pathological, and imaging data of 83 patients with HCC confirmed by postoperative pathology were analyzed, and the patients were randomly divided into a training set (n = 58) and a validation set (n = 25) at a ratio of 7:3. All patients underwent a magnetic resonance imaging (MRI) scan that included multi-b value diffusion-weighted scanning before surgery, and quantitative parameters were obtained via intravoxel incoherent motion (IVIM) and diffusion kurtosis (DKI) models. Univariate and multivariate logistic regression analyses were conducted using the training set data to construct a model, which was internally validated. The area under the curve (AUC) of the receiver operating characteristics (ROC), a decision curve analysis (DCA), and a calibration analysis were used to evaluate the model's performance. Additionally, for patients with available follow-up data, the combined model was evaluated for its potential utility in predicting the one-year recurrence risk by analyzing the area under the curve (AUC) of the receiver operating characteristic (ROC) curve.The combined model outperformed the clinicaland parametric models in predicting high Ki67 expression. The nomograms based on the combined model included the neutrophil-to-lymphocyte ratio (NLR), ADCslow_Aver. The model showed strong discrimination in the training set, with an AUC of 0.836 (95% CI: 0.729-0.942) and acceptable calibration (Hosmer-Lemeshow p = 0.109). In the validation set, the model maintained moderate discrimination (AUC 0.806, 95% CI: 0.621-0.990) with good calibration (p = 0.663). DCA revealed that the combined model provided good clinical value and correction effects. Additionally, when used to predict the one-year recurrence risk, the combined model achieved moderate accuracy (AUC = 0.747), highlighting its potential utility in identifying patients at a higher risk of recurrence. A nomogram incorporating the NLR and quantitative MR diffusion parameters effectively predicts Ki67 expression in HCC patients before surgery. The model also shows promise in predicting recurrence risk, which may aid in postoperative risk stratification and patient management. Clinical Relevance Statement We established a model that incorporated the NLR and quantitative magnetic resonance diffusion parameters, which demonstrated robust performance in predicting both high Ki67 expression and the one-year recurrence risk in HCC patients. This model shows potential clinical value in guiding postoperative risk stratification and personalized treatment planning.
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Affiliation(s)
- Yu-Chen Wei
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Liang Yun
- Department of Radiology, Guilin Municipal Hospital of Traditional Chinese Medicine, Guilin, China
| | - Yan-Ling Liang
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | | | - Chongze Yang
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Yuan-Fang Tao
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Sheng-Chen Jiang
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Jin-Yuan Liao
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Ministry of Education, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China.
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Zeng ZX, Wu JY, Wu JY, Zhang ZB, Wang K, Zhuang SW, Li B, Zhou JY, Lin ZT, Li SQ, Li YN, Fu YK, Yan ML. Prognostic Value of Pathological Response for Patients with Unresectable Hepatocellular Carcinoma Undergoing Conversion Surgery. Liver Cancer 2024; 13:498-508. [PMID: 39435272 PMCID: PMC11493390 DOI: 10.1159/000536376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Accepted: 01/17/2024] [Indexed: 10/23/2024] Open
Abstract
Introduction Transarterial chemoembolization combined with lenvatinib and PD-1 inhibitor (triple therapy) has displayed encouraging clinical outcomes for unresectable hepatocellular carcinoma (uHCC). We aimed to explore the prognostic value of pathological response (PR) in patients with initially uHCC who underwent conversion surgery following triple therapy and identify predictors of major pathological response (MPR). Methods A total of 76 patients with initially uHCC who underwent conversion surgery following triple therapy were retrospectively analyzed. PR was calculated as the proportion of nonviable tumor cell surface area of the whole tumor bed surface area. MPR was identified when PR was ≥90%. Pathological complete response (pCR) was defined as the absence of viable tumor cells. Results MPR and pCR were identified in 53 (69.7%) and 25 (32.9%) patients, respectively. The 1- and 2-year overall survival in patients with MPR were significantly higher than in those without MPR (100.0% and 91.3% vs. 67.7% and 19.4%; p < 0.001). The corresponding recurrence-free survival was also improved in patients with MPR compared to those without (75.9% and 50.8% vs. 22.3% and 11.2%; p < 0.001). Similar results were observed among patients with pCR and those without. Patients who achieved MPR without pCR exhibited survival rates comparable to those of patients who achieved pCR. Baseline neutrophil-to-lymphocyte ratio ≥2.6 (p = 0.016) and preoperative alpha-fetoprotein level ≥400 ng/mL (p = 0.015) were independent predictors of MPR. Conclusion The presence of MPR or pCR could improve prognosis in patients with initially uHCC who underwent conversion surgery following triple therapy. The PR may become a surrogate marker for predicting the prognosis of these patients.
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Affiliation(s)
- Zhen-Xin Zeng
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
| | - Jia-Yi Wu
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Jun-Yi Wu
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Zhi-Bo Zhang
- Department of Hepatopancreatobiliary Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Kai Wang
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Shao-Wu Zhuang
- Department of Interventional Radiology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China
| | - Bin Li
- Department of Hepato-Biliary-Pancreatic and Vascular Surgery, First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Jian-Yin Zhou
- Department of Hepatobiliary Surgery, Zhongshan Hospital of Xiamen University, Xiamen, China
| | - Zhong-Tai Lin
- Department of General Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Shu-Qun Li
- Department of Hepatobiliary Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Yi-Nan Li
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
| | - Yang-Kai Fu
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
| | - Mao-Lin Yan
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, China
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Wen S, Chen Y, Hu C, Du X, Xia J, Wang X, Zhu W, Wang Q, Zhu M, Chen Y, Shen B. Combination of Tertiary Lymphoid Structure and Neutrophil-to-Lymphocyte Ratio Predicts Survival in Patients With Hepatocellular Carcinoma. Front Immunol 2022; 12:788640. [PMID: 35095864 PMCID: PMC8793028 DOI: 10.3389/fimmu.2021.788640] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2021] [Accepted: 12/20/2021] [Indexed: 11/13/2022] Open
Abstract
Background Hepatocellular carcinoma (HCC) is the most common pathological type of primary liver cancer. The lack of prognosis indicators is one of the challenges in HCC. In this study, we investigated the combination of tertiary lymphoid structure (TLS) and several systemic inflammation parameters as a prognosis indicator for HCC. Materials and Methods We retrospectively recruited 126 postoperative patients with primary HCC. The paraffin section was collected for TLS density assessment. In addition, we collected the systemic inflammation parameters from peripheral blood samples. We evaluated the prognostic values of those parameters on overall survival (OS) using Kaplan-Meier curves, univariate and multivariate Cox regression. Last, we plotted a nomogram to predict the survival of HCC patients. Results We first found TLS density was positively correlated with HCC patients’ survival (HR=0.16, 95% CI: 0.06 − 0.39, p < 0.0001), but the power of TLS density for survival prediction was found to be limited (AUC=0.776, 95% CI:0.772 − 0.806). Thus, we further introduced several systemic inflammation parameters for survival analysis, we found neutrophil-to-lymphocyte ratio (NLR) was positively associated with OS in univariate Cox regression analysis. However, the combination of TLS density and NLR better predicts patient’s survival (AUC=0.800, 95% CI: 0.698-0.902, p < 0.001) compared with using any single indicator alone. Last, we incorporated TLS density, NLR, and other parameters into the nomogram to provide a reproducible approach for survival prediction in HCC clinical practice. Conclusion The combination of TLS density and NLR was shown to be a good predictor of HCC patient survival. It also provides a novel direction for the evaluation of immunotherapies in HCC.
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Affiliation(s)
- Shaodi Wen
- The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China
| | - Yuzhong Chen
- The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China
| | - Chupeng Hu
- Key Laboratory of Microenvironment and Major Diseases, Department of Immunology, Nanjing Medical University, Nanjing, China
| | - Xiaoyue Du
- The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China
| | - Jingwei Xia
- The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China
| | - Xin Wang
- The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China
| | - Wei Zhu
- School of Medicine, Jiangsu University, Zhenjiang, China
| | - Qingbo Wang
- Department of Chemotherapy, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Miaolin Zhu
- The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China
| | - Yun Chen
- The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China.,Key Laboratory of Microenvironment and Major Diseases, Department of Immunology, Nanjing Medical University, Nanjing, China.,Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Bo Shen
- The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China
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Mouchli M, Reddy S, Gerrard M, Boardman L, Rubio M. Usefulness of neutrophil-to-lymphocyte ratio (NLR) as a prognostic predictor after treatment of hepatocellular carcinoma." Review article. Ann Hepatol 2021; 22:100249. [PMID: 32896610 DOI: 10.1016/j.aohep.2020.08.067] [Citation(s) in RCA: 69] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2020] [Revised: 08/07/2020] [Accepted: 08/08/2020] [Indexed: 02/06/2023]
Abstract
The neutrophil-to-lymphocyte ratio (NLR) is an inflammatory marker which has been investigated as a prognostic indicator in post-therapeutic recurrence and survival of patients with HCC. Our aim was to review all studies that assessed the prognostic value of pre-treatment NLR in predicting patient survival, cancer recurrence, and graft survival in patients undergoing various therapies for HCC. We searched the database of PubMed and Google Scholar to review all studies that have the word "NLR" and the word "HCC." We included all studies that assessed pre-treatment NLR as a prognostic factor in predicting outcomes in HCC patients. We excluded studies that assessed the correlation between post-treatment NLR or dynamic changes in NLR after treatment and HCC outcomes in an effort to minimize the confounding effect of each treatment on NLR. We reviewed 123 studies that studied the correlation between pre-treatment NLR and patient survival, 72 studies that evaluated the correlation between pre-treatment NLR and tumor recurrence, 21 studies that evaluated the correlation between NLR and tumor behavior, and 4 studies that assessed the correlation between NLR and graft survival. We found a remarkable heterogeneity between the methods of the studies, which is likely responsible for the differences in outcomes. The majority of the studies suggested a correlation between higher levels of pre-treatment NLR and poor outcomes. We concluded that NLR is a reliable and inexpensive biomarker and should be incorporated into other prognostic models to help determine outcomes following HCC treatment.
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Affiliation(s)
- Mohamad Mouchli
- Virginia Tech Carilion School of Medicine Department of Internal Medicine, Division of Gastroenterology & Hepatology, Roanoke, VA, United States; Virginia Tech Carilion School of Medicine Department of Internal Medicine, Roanoke, VA, United States; Mayo Clinic, Division of Gastroenterology & Hepatology, Rochester, MN, United States; Cleveland Clinic Foundation, Division of Gastroenterology & Hepatology, Cleveland, OH, United States.
| | - Shravani Reddy
- Virginia Tech Carilion School of Medicine Department of Internal Medicine, Roanoke, VA, United States
| | - Miranda Gerrard
- Virginia Tech Carilion School of Medicine, Roanoke, VA, United States
| | - Lisa Boardman
- Mayo Clinic, Division of Gastroenterology & Hepatology, Rochester, MN, United States
| | - Marrieth Rubio
- Virginia Tech Carilion School of Medicine Department of Internal Medicine, Division of Gastroenterology & Hepatology, Roanoke, VA, United States; Virginia Tech Carilion School of Medicine Department of Internal Medicine, Roanoke, VA, United States
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Glasgow Prognostic Score and modified Glasgow Prognostic Score and survival in patients with hepatocellular carcinoma: a meta-analysis. BMJ Open 2021. [PMCID: PMC8718431 DOI: 10.1136/bmjopen-2021-053061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
Objective To evaluate the association between inflammation-related markers, modified Glasgow Prognostic Score (mGPS) and Glasgow Prognostic Score (GPS), and survival outcome and recurrence risk in patients with hepatocellular carcinoma (HCC) after treatment. Design Systematic reviews and meta-analysis of cohort studies. Date sources Embase, Scopus, Web of Science and PubMed were searched through 10 March 2021. Eligibility criteria We included cohort studies that assessed the effect of pretreatment mGPS/GPS levels on survival outcomes in patients with HCC. Data extraction and synthesis Two researchers independently selected the data and reached a consensus. In case of disagreement, a third researcher was required to assist. The HRs and 95% CIs were used as the effect size indexes. Newcastle-Ottawa Scale was used to assess risk of bias and quality assessment of the included studies. Results The meta-analysis included 23 studies, most of which were retrospective. Participants were grouped according to the score of mGPS/GPS. When analysed into two groups (1/2 vs 0), the results showed that patients with a mGPS/GPS of 1 or 2 had poorer overall survival (OS) than those with a score of 0 (both p<0.001). When analysed into three groups (1 vs 0 and 2 vs 0), the results revealed that an mGPS/GPS of 2 is related to poorer OS in patients with HCC (HR=2.46, 95% CI 2.06 to 2.95, and HR=3.45, 95% CI 1.68 to 7.10, respectively). However, a GPS of 1 (p=0.005) but not an mGPS of 1 (p=0.177) had a significant association with OS. No association was found between mGPS/GPS and disease-free survival or recurrence-free survival. Conclusion GPS was more closely associated the survival in patients with HCC than mGPS. A higher GPS has an association with poorer survival. It can be combined with tumour staging to assess the OS of HCC more accurately. PROSPERO registration number CRD42021242049.
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Lu LH, Wei W, Li SH, Zhang YF, Guo RP. The lymphocyte-C-reactive protein ratio as the optimal inflammation-based score in patients with hepatocellular carcinoma underwent TACE. Aging (Albany NY) 2021; 13:5358-5368. [PMID: 33589570 PMCID: PMC7950222 DOI: 10.18632/aging.202468] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Accepted: 12/16/2020] [Indexed: 02/07/2023]
Abstract
The lymphocyte-C-reactive protein ratio (LCR) is a recently described inflammation-based score, and it remains unclear which is the optimal inflammation-based score among patients with hepatocellular carcinoma (HCC) who underwent transarterial chemoembolization (TACE). A large cohort of HCC patients (n=1625) who underwent TACE as the initial treatment were enrolled in the present study. Inflammation-based scores, including the Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), high-sensitivity modified Glasgow Prognostic Score (Hs-mGPS), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), and LCR, were all related to the survival of HCC patients, but only the LCR score was a significant and independent predictor in multivariate analysis (hazard ratio: 1.45; 95% confidence interval: 1.27-1.65; P<0.001). Further analysis showed that the LCR score stably and consistently differentiated subgroup patients with distinct prognoses. The predictive accuracies of the LCR score (0.70, 0.68, and 0.68 for 1-, 3-, and 5-year C-index, respectively) were superior to the other inflammatory-based scores (0.60-0.64, 0.58-0.62, and 0.58-0.62 for 1-, 3-, and 5-year C-index, respectively). The LCR score was an independent prognostic indicator for HCC patients who underwent TACE, and it was superior to the other inflammation-based scores in prognostic ability.
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Affiliation(s)
- Liang-He Lu
- Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
| | - Wei Wei
- Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
| | - Shao-Hua Li
- Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
| | - Yong-Fa Zhang
- Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Rong-Ping Guo
- Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
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Gao K, Cheng H, Bhushan S, Li N, Xiao Z. Preoperative neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio are correlated with tumor–node–metastasis stages in patients with non-small cell lung cancer. J Cancer Res Ther 2021; 18:1666-1673. [DOI: 10.4103/jcrt.jcrt_473_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
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The prognostic significance of inflammation-based scores in patients with ampullary carcinoma after pancreaticoduodenectomy. BMC Cancer 2020; 20:981. [PMID: 33036573 PMCID: PMC7547453 DOI: 10.1186/s12885-020-07482-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Accepted: 10/01/2020] [Indexed: 12/11/2022] Open
Abstract
Background Growing evidence indicates that the systemic inflammatory response plays an important role in cancer development and progression. Several inflammatory markers have been reported to be associated with clinical outcomes in patients with various types of cancer. This study was designed to evaluate the prognostic value of inflammatory indexes in patients with ampullary cancer (AC) who underwent pancreaticoduodenectomy (PD). Methods We retrospectively reviewed the data of 358 patients with AC who underwent PD between 2009 and 2018. R software was used to compare the area under the time-dependent receiver operating characteristic (ROC) curves (AUROCs) of the inflammation-based indexes, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), modified Glasgow Prognostic Score (mGPS), prognostic nutritional index (PNI) and prognostic index (PI), in terms of their predictive value for survival. The survival differences of these indexes were compared by the Kaplan-Meier method and univariate and multivariate analyses were performed to determine the prognostic factors of disease-free survival (DFS) and overall survival (OS). Results The estimated 1-, 2-, and 3-year OS and DFS rates were 83.9, 65.8, and 55.2% and 58.0, 42.8, and 37.8%, respectively, for the entire cohort. The survival differences were significant in terms of OS and DFS when patients were stratified by these inflammation-based indexes. The comparisons of the AUROCs of these inflammation-based indexes illustrated that NLR and PI displayed the highest prognostic value, compared to the other indexes. When NLR and PI were combined, NLR-PI showed even higher AUROC values and was identified as a significant prognostic factor for OS and DFS. Conclusion Specific inflammatory indexes, such as NLR, PLR and dNLR, were found to be able to predict the OS or DFS of patients. As a novel inflammatory index, the level of NLR-PI, which can be regarded as a more useful prognostic index, exhibited strong predictive power for predicting the prognosis of patients with AC after the PD procedure.
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Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as predictors of tumor response in hepatocellular carcinoma after DEB-TACE. Eur Radiol 2020; 30:5663-5673. [PMID: 32424595 DOI: 10.1007/s00330-020-06931-5] [Citation(s) in RCA: 79] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Revised: 03/15/2020] [Accepted: 04/30/2020] [Indexed: 02/08/2023]
Abstract
OBJECTIVES To investigate the predictive value of quantifiable imaging and inflammatory biomarkers in patients with hepatocellular carcinoma (HCC) for the clinical outcome after drug-eluting bead transarterial chemoembolization (DEB-TACE) measured as volumetric tumor response and progression-free survival (PFS). METHODS This retrospective study included 46 patients with treatment-naïve HCC who received DEB-TACE. Laboratory work-up prior to treatment included complete and differential blood count, liver function, and alpha-fetoprotein levels. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were correlated with radiomic features extracted from pretreatment contrast-enhanced magnetic resonance imaging (MRI) and with tumor response according to quantitative European Association for the Study of the Liver (qEASL) criteria and progression-free survival (PFS) after DEB-TACE. Radiomic features included single nodular tumor growth measured as sphericity, dynamic contrast uptake behavior, arterial hyperenhancement, and homogeneity of contrast uptake. Statistics included univariate and multivariate linear regression, Cox regression, and Kaplan-Meier analysis. RESULTS Accounting for laboratory and clinical parameters, high baseline NLR and PLR were predictive of poorer tumor response (p = 0.014 and p = 0.004) and shorter PFS (p = 0.002 and p < 0.001). When compared to baseline imaging, high NLR and PLR correlated with non-spherical tumor growth (p = 0.001 and p < 0.001). CONCLUSIONS This study establishes the prognostic value of quantitative inflammatory biomarkers associated with aggressive non-spherical tumor growth and predictive of poorer tumor response and shorter PFS after DEB-TACE. KEY POINTS • In treatment-naïve hepatocellular carcinoma (HCC), high baseline platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) are associated with non-nodular tumor growth measured as low tumor sphericity. • High PLR and NLR are predictive of poorer volumetric enhancement-based tumor response and PFS after DEB-TACE in HCC. • This set of readily available, quantitative immunologic biomarkers can easily be implemented in clinical guidelines providing a paradigm to guide and monitor the personalized application of loco-regional therapies in HCC.
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The prevalence of cancer associated systemic inflammation: Implications of prognostic studies using the Glasgow Prognostic Score. Crit Rev Oncol Hematol 2020; 150:102962. [PMID: 32344318 DOI: 10.1016/j.critrevonc.2020.102962] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Revised: 04/08/2020] [Accepted: 04/08/2020] [Indexed: 02/07/2023] Open
Abstract
The prognostic importance of SIR in patients with cancer is widely recognised. More recently it has become clear that the systemic inflammatory response is an important etiologic factor in the development of cancer cachexia. Two recent meta-analysis carried out in 2017 and 2018 were interrogated and the number of patients with specific cancer types were identified. The percentage of patients with operable cancer (n>28,000) who were systemically inflamed varied from 21% to 38%. The percentage of patients with inoperable cancer (n>12,000) who were systemically inflamed varied from 29% to 79%. Overall, the percentage of patients (n>40,000) who were systemically inflamed varied from 28% to 63% according to tumour type. The most commonly studied cancer was colorectal cancer (n∼10,000 patients) and 40% were systemically inflamed.
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Wang C, Wang M, Zhang X, Zhao S, Hu J, Han G, Liu L. The neutrophil-to-lymphocyte ratio is a predictive factor for the survival of patients with hepatocellular carcinoma undergoing transarterial chemoembolization. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:541. [PMID: 32411764 PMCID: PMC7214899 DOI: 10.21037/atm.2020.02.113] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Background Neutrophil-to-lymphocyte ratio (NLR) is considered as a prognostic predictor of hepatocellular carcinoma (HCC). However, its prognostic ability is still controversial. This study aimed to evaluate the prognostic value of NLR changes in HCC patients undergoing transarterial chemoembolization (TACE). Methods The patients who were newly diagnosed with HCC and treated with TACE in our center from July 2010 to December 2014 were enrolled in the study. The factors, including NLR, were recorded at baseline and three days and one month after TACE. Results A total of 380 consecutive patients were studied retrospectively. The median NLR values at baseline, 3 days and 1 month after TACE (2.4, 6.3 and 2.4 respectively), were used as the cut-off value for patient stratification. Compared with the patients in low NLR group, those with high NLR had a larger tumor size. For baseline measurement, the low NLR group showed improved overall survival (OS) compared with the high group (median OS, 27.1 vs. 15.6 months, P=0.004). There was no survival difference between the low and high NLR groups when measured at 3 days and at 1 month after TACE (P>0.05). Multivariate analysis showed that baseline NLR >2.4 was an independent prognostic predictor of poor OS. There was significant survival difference between the normal NLR group and the high or increased NLR group, with a median OS of 29.1 and 19.1 months, respectively (P=0.023). Conclusions The dynamic changes of baseline NLR are significantly associated with OS in HCC patients treated with TACE, and as a result patient selection and prognostic prediction may be refined.
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Affiliation(s)
- Chengguo Wang
- Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China
| | - Mengmeng Wang
- Department of Drug and Equipment, Aeromedicine Identification and Training Centre of Air Force, Xi'an 710069, China
| | - Xiangnan Zhang
- Division of Scientific Research, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China
| | - Shoujie Zhao
- Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China
| | - Jie Hu
- Department of Clinical laboratory, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China
| | - Guohong Han
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an 710032, China
| | - Lei Liu
- Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China
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Li L, Chan SL, Mo F, Hui EP, Koh J, Chan AK, Tang NL, Chu CM, Hui J, Lee KF, Yu S, Yeo W. Status of inflammation in relation to health related quality of life in hepatocellular carcinoma patients. Qual Life Res 2019; 28:2597-2607. [PMID: 31037590 DOI: 10.1007/s11136-019-02190-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/23/2019] [Indexed: 12/17/2022]
Abstract
PURPOSE Both Inflammation and health-related quality of life (HRQoL) are independent prognosticators in HCC patients. We hypothesized that inflammation can cause impairment in HRQoL and investigated the correlation between inflammatory status and HRQoL in HCC patients. METHODS Clinical, laboratory and HRQoL (using EORTC QLQ-C30, QLQ-HCC18, C30 and HCC18 index-scores) data were prospectively collected from HCC patients at diagnosis. Correlation analyses were performed between HRQoL and inflammation-based markers including C-reactive protein (CRP), CRP/albumin ratio (CRP/alb), Glasgow Prognostic Score (GPS), Inflammation-Based Index (IBI) and Prognostic Index (PI). RESULTS Among 445 HCC patients, higher inflammatory states were significantly correlated with worse HRQoL. For CRP and CRP/alb ratio, the HRQoL factors with higher correlations included C30 and HCC18 index-scores, certain QLQ-C30 domains and items ('physical functioning', 'role functioning', 'fatigue', 'pain', 'appetite loss') and QLQ-HCC18 items ('fatigue', 'body image', 'nutrition' and 'abdominal swelling'), where the Pearson's correlation coefficients were up to 0.416. Multivariate analyses indicated that worse HRQoL factors were significantly correlated with worse scores in GPS, IBI and PI. CONCLUSION In HCC patients, inflammatory status correlates with HRQoL at presentation. In particular, relatively stronger correlations with CRP-based markers have been observed in HRQoL scales that assess constitutional symptoms (QLQ-C30 'physical functioning', 'role functioning', 'fatigue', 'appetite loss' and QLQ-HCC18 'fatigue' and 'nutrition') and tumor burden (QLQ-C30 'pain' and QLQ-HCC18 'abdominal swelling' and 'body image'). Future studies are warranted to evaluate whether intervention that reduces inflammation could improve HRQoL in HCC patients.
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Affiliation(s)
- Leung Li
- State Key Laboratory of Translational Oncology, Department of Clinical Oncology, Faculty of Medicine, Prince of Wales Hospital, Hong Kong Cancer Institute, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, Hong Kong
| | - Stephen L Chan
- State Key Laboratory of Translational Oncology, Department of Clinical Oncology, Faculty of Medicine, Prince of Wales Hospital, Hong Kong Cancer Institute, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, Hong Kong
| | - Frankie Mo
- State Key Laboratory of Translational Oncology, Department of Clinical Oncology, Faculty of Medicine, Prince of Wales Hospital, Hong Kong Cancer Institute, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, Hong Kong
| | - Edwin P Hui
- State Key Laboratory of Translational Oncology, Department of Clinical Oncology, Faculty of Medicine, Prince of Wales Hospital, Hong Kong Cancer Institute, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, Hong Kong
| | - Jane Koh
- State Key Laboratory of Translational Oncology, Department of Clinical Oncology, Faculty of Medicine, Prince of Wales Hospital, Hong Kong Cancer Institute, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, Hong Kong
| | - Allen Kc Chan
- Department of Chemical Pathology, Faculty of Medicine, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong
| | - Nelson Ls Tang
- Department of Chemical Pathology, Faculty of Medicine, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong
| | - Cheuk M Chu
- Department of Imaging and Interventional Radiology, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong
| | - Joyce Hui
- Department of Imaging and Interventional Radiology, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong
| | - Kit F Lee
- Department of Surgery, Prince of Wales Hospital, Shatin, Hong Kong SAR, Hong Kong
| | - Simon Yu
- Department of Imaging and Interventional Radiology, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong
| | - Winnie Yeo
- State Key Laboratory of Translational Oncology, Department of Clinical Oncology, Faculty of Medicine, Prince of Wales Hospital, Hong Kong Cancer Institute, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, Hong Kong.
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13
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Deciphering Platelet Kinetics in Diagnostic and Prognostic Evaluation of Hepatocellular Carcinoma. Can J Gastroenterol Hepatol 2018; 2018:9142672. [PMID: 30050894 PMCID: PMC6040256 DOI: 10.1155/2018/9142672] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2018] [Accepted: 04/23/2018] [Indexed: 02/06/2023] Open
Abstract
Liver pathophysiology can, directly and indirectly, impose morphological or biochemical abnormalities of the platelets. Conversely, platelets are also able to regulate the promitogenic and profibrotic signals on liver pathobiology. Platelet contribution to the liver pathophysiology is typically facilitated by the platelet-derived growth factors that are sequestered in different subsets of alpha and dense granules, and the release of these growth factors is synchronized according to the stage and type of liver disease or injury. Thus, platelets harbor clinically relevant information with potential diagnostic and prognostic implications in liver diseases. Hepatocellular carcinoma (HCC) largely influences the platelet kinetics, and a growing body of evidence has recognized its association with HCC occurrence or prognosis. This narrative review summarizes the progress made on implicating platelet as a diagnostic and prognostic tool for HCC; the review also dissects the contradictory results from earlier studies and reflects how combining platelet-based information may enable more reliable test for diagnostic and prognostic evaluation of HCC.
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14
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Ventura Y, Carr BI, Kori I, Guerra V, Shibolet O. Analysis of aggressiveness factors in hepatocellular carcinoma patients undergoing transarterial chemoembolization. World J Gastroenterol 2018; 24:1641-1649. [PMID: 29686471 PMCID: PMC5910547 DOI: 10.3748/wjg.v24.i15.1641] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2018] [Revised: 03/10/2018] [Accepted: 03/25/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate novel predictors of survival in hepatocellular carcinoma (HCC) patients following transarterial chemoembolization (TACE).
METHODS One hundred sixty seven patients with un-resectable HCC were retrospectively analyzed to identify factors that might contribute to their HCC biology and aggressiveness. We correlated routine laboratory results (total bilirubin, AST, ALKP, GGTP, albumin etc.) to maximum tumor diameter, number of tumor nodules, portal vein thrombosis and blood alpha-fetoprotein levels. These 4 parameters were previously combined to form an aggressiveness index (AgI). We used The Wilcoxon rank-sum (Mann-Whitney), to test the correlation between the AgI categories and liver function parameters. The Cox proportional hazards model was applied to evaluate the categories of AgI associated with overall survival.
RESULTS The AgI was strongly correlated with survival in this novel patient population. Three year survival probability for AgI > or < 4 was 42.4% vs 61.8%; P < 0.0863 respectively. Several factors independently correlated with AgI using univariate multiple logistic regression of AgI with 8 laboratory parameters. Lower albumin levels had an OR of 2.56 (95%CI: 1.120-5.863 P < 0.026), elevated Alkaline phosphatase and gamma glutamyl transpeptidase (GGTP) had ORs of 1.01 (95%CI: 1.003-1.026, P < 0.017) and 0.99 (95%CI: 0.99-1.00, P < 0.053) respectively. In a Cox proportional hazard model combining mortality for AgI score and liver function parameters, only GGTP levels and the AgI were independently associated with survival. An AgI > 4 had HR for mortality of 2.18 (95%CI: 1.108-4.310, P < 0.024). GGTP’s single unit change had a HR for mortality of 1.003 (95%CI: 1.001-1.006, P < 0.016). These were considered in the final multivariate model with the total cohort. An AgI > 4 had a HR for mortality of 2.26 (95%CI: 1.184-4.327, P < 0.016). GGTP had a HR of 1.003 (95%CI: 1.001-1.004, P < 0.001).
CONCLUSION Our study validates the AgI in a new population with un-resectable HCC patients undergoing TACE. The analysis establishes a correlation between GGTP and the AgI.
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Affiliation(s)
- Yossi Ventura
- Liver Unit, Department of Gastroenterology and Hepatology, Tel-Aviv Medical Center, Tel-Aviv 62431, Israel
- Sackler faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel
| | - Brian I Carr
- Izmir Biomedicine and Genome Center, Dokuz Eylul University, Izmir 35340, Turkey
| | - Issac Kori
- Interventional Radiology, Division of Imaging Tel Aviv Medical Center, Tel-Aviv 62431, Israel
| | - Vito Guerra
- Department of Clinical Trials and Epidemiology, IRCCS de Bellis, Castellana Grotte 70013, Italy
| | - Oren Shibolet
- Liver Unit, Department of Gastroenterology and Hepatology, Tel-Aviv Medical Center, Tel-Aviv 62431, Israel
- Sackler faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel
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15
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Serum albumin levels in relation to tumor parameters in hepatocellular carcinoma patients. Int J Biol Markers 2017; 32:e391-e396. [PMID: 28862714 DOI: 10.5301/ijbm.5000300] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/24/2017] [Indexed: 12/18/2022]
Abstract
BACKGROUND Serum albumin levels have been shown to have prognostic significance in hepatocellular carcinoma (HCC), as part of an inflammatory index. The aim of this study was to examine the possible relationship of serum albumin levels to parameters of HCC aggressiveness. METHODS A large HCC patient cohort was retrospectively examined, and the possible relationships of albumin levels to tumor diameter, multifocality, portal vein thrombosis (PVT) and α-fetoprotein levels were examined. RESULTS HCC patients with lower serum albumin levels had significantly larger maximum tumor diameters, greater prevalence of PVT, increased tumor multifocality and higher α-fetoprotein levels, than HCC patients with higher albumin levels. A correlation was found between levels of these tumor parameters and serum albumin levels. CONCLUSIONS These results indicate that low serum albumin levels correlate with increased parameter measures of HCC aggressiveness, in addition to their role as a monitor of systemic inflammation. Decreased serum albumin might have a role in HCC aggressiveness.
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Zhao Y, Si G, Zhu F, Hui J, Cai S, Huang C, Cheng S, Fathy AH, Xiang Y, Li J. Prognostic role of platelet to lymphocyte ratio in hepatocellular carcinoma: a systematic review and meta-analysis. Oncotarget 2017; 8:22854-22862. [PMID: 28206965 PMCID: PMC5410268 DOI: 10.18632/oncotarget.15281] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2016] [Accepted: 01/29/2017] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND AND AIMS Several studies were conducted to explore the prognostic significance of platelet to lymphocyte ratio (PLR) in hepatocellular carcinoma (HCC), however, contradictory results across most reports were documented. To this end, we present a systematic review that aims to summarize the prognostic significance of PLR in patients with HCC. RESULTS A total of 10 studies involving a total of 2,315 patients were identified. The Newcastle-Ottawa Quality Assessment Scale (NOS) of each included study was greater than or equal to 5. The results indicated that high PLR was significantly associated with a worse OS when compared to the low PLR (HR = 1.60, 95% CI = 1.23-2.08, p = 0.0005; I2 = 88%, p < 0.00001). Similar results were detected in the subgroup analysis of the analysis model, cut-off value, ethnicity, sample size and therapy. However, no obvious correlation between the PLR and DFS/RFS in patients with HCC was observed (HR = 1.21, 95% CI = 0.87-1.67, p = 0.26; I2 = 61%, p = 0.07). MATERIALS AND METHODS A complete literature search in the PubMed, Cochrane Library and Embase database was performed. Retrospective and prospective studies focusing on the role of PLR on the prognosis in HCC were all deemed as "suitable" for our scope. The endpoints determined were: the overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS) and the progress free survival (PFS). CONCLUSIONS The study revealed that high PLR is an unfavorable predictor of OS in patients with HCC, and high PLR is a promising prognostic biomarker for HCC, especially for patients in Asia.
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Affiliation(s)
- Yongzhao Zhao
- School of Medicine, Tongji University, Shanghai, China
| | - Guangyan Si
- Department of Interventional Radiology, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, China
| | - Fengshang Zhu
- Department of Gastroenterology, Tongji Hospital, Tongji University, Shanghai, China
| | - Jialiang Hui
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Shangli Cai
- Mental Health Institute of the Second Xiangya Hospital, National Technology Institute of Psychiatry, Key Laboratory of Psychiatry and Mental Health of Hunan Province, Central South University, Hunan, China
| | | | - Sijin Cheng
- School of Medicine, Tongji University, Shanghai, China
| | | | - Yi Xiang
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jing Li
- Department of Gastroenterology, Tongji Hospital, Tongji University, Shanghai, China
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17
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Le PH, Liang KH, Chang ML, Hsu CW, Chen YC, Lin CL, Lin WR, Lai MW, Yeh CT. Clinical Predictors for Neutrophil-to-Lymphocyte Ratio Changes in Patients with Chronic Hepatitis B Receiving Peginterferon Treatment. In Vivo 2017; 31:723-729. [PMID: 28652447 PMCID: PMC5566930 DOI: 10.21873/invivo.11121] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2017] [Revised: 04/10/2017] [Accepted: 04/11/2017] [Indexed: 12/18/2022]
Abstract
BACKGROUND A lower neutrophil-to-lymphocyte ratio (NLR) was found to be associated with better clinical outcomes in hepatitis B-related liver cirrhosis and hepatocellular carcinoma. We aimed to identify pre-therapeutic variables capable of predicting NLR changes in patients with hepatitis B receiving peginterferon therapy. PATIENTS AND METHODS The baseline clinicopathological data were analyzed to correlate with NLR changes before and 1 year after peginterferon treatment in 71 patients with hepatitis B. RESULTS Univariate analysis revealed that pre-treatment NLR itself negatively predicted NLR changes following peginterferon treatment (odds ratio(OR)=0.320, p=0.013). Further analysis identified pre-treatment NLR, hemoglobin and hepatitis B surface antigen level as independent predictors for NLR changes (adjusted p=0.028, 0.005, and 0.028, respectively). A predictive score composed of these three factors had an area under the curve of 76.5% (p<0.001). CONCLUSION Pretreatment NLR, hemoglobin and hepatitis B surface antigen level in combination, effectively predicted NLR changes following peginterferon treatment.
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Affiliation(s)
- Puo-Hsien Le
- Liver Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C
| | - Kung-Hao Liang
- Liver Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C
- Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan, R.O.C
| | - Ming-Ling Chang
- Liver Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C
| | - Chao-Wei Hsu
- Liver Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C
| | - Yi-Cheng Chen
- Liver Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C
| | - Chih-Lang Lin
- Liver Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C
| | - Wey-Ran Lin
- Liver Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C
| | - Ming-Wei Lai
- Liver Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C
| | - Chau-Ting Yeh
- Liver Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C.
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C
- Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan, R.O.C
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18
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He CB, Lin XJ. Inflammation scores predict the survival of patients with hepatocellular carcinoma who were treated with transarterial chemoembolization and recombinant human type-5 adenovirus H101. PLoS One 2017; 12:e0174769. [PMID: 28355305 PMCID: PMC5371390 DOI: 10.1371/journal.pone.0174769] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2016] [Accepted: 03/15/2017] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The systemic inflammatory response plays an important role in cancer development and progression. An original inflammation-based staging system for predicting survival in patients undergoing transarterial chemoembolization (TACE) combined with recombinant human type-5 adenovirus H101 is not available. This study aimed to validate the prognostic value of inflammation scores for patients with hepatocellular carcinoma (HCC) who were treated with TACE combined with H101. METHODS The data from 216 patients with HCC who underwent TACE combined with H101 from January 2007 to July 2015 were retrospectively collected, and the association of the inflammation scores with overall survival (OS) was analyzed. Univariate and multivariate analyses were performed to identify variables associated with OS. The prognostic value of the inflammation scores, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), neutrophil/ platelet-to-lymphocyte ratio (NLR-PLR), modified Glasgow Prognostic Score (mGPS), prognostic nutritional index (PNI), prognostic index (PI), tumor-node-metastasis (TNM), Barcelona Clinic Liver Cancer (BCLC) and Cancer of the Liver Italian Program (CLIP) staging systems were analyzed and compared using the areas under the receiver operating characteristic curves (AUROCs). RESULTS The estimated 1-, 2-, and 3-year OS rates were 61.3%, 44.2%, and 40.5% for the entire study cohort, respectively; the median OS was 17 months. According to the multivariate Cox proportional hazards model, the pretreatment NLR, tumor diameter and pretreatment alpha-fetoprotein (AFP) levels were independent predictors of OS. The CLIP score had superior discriminative abilities compared with other staging systems, and the NLR-PLR score consistently displayed a higher AUROC value than the other inflammation-based prognostic scores. The combination of the NLR-PLR and CLIP scores exhibited a superior prognostic ability for OS compared to the NLR-PLR or CLIP scores alone. CONCLUSIONS The NLR-PLR score is a more powerful predictive system than the other inflammation-based scores for patients with HCC who were treated with TACE and H101. The predictive ability may be improved by utilizing a combination of the NLR-PLR and CLIP scores.
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Affiliation(s)
- Chao-Bin He
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, P.R. China
| | - Xiao-Jun Lin
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, P.R. China
- * E-mail:
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Qi X, Li J, Deng H, Li H, Su C, Guo X. Neutrophil-to-lymphocyte ratio for the prognostic assessment of hepatocellular carcinoma: A systematic review and meta-analysis of observational studies. Oncotarget 2016; 7:45283-45301. [PMID: 27304193 PMCID: PMC5216723 DOI: 10.18632/oncotarget.9942] [Citation(s) in RCA: 73] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2016] [Accepted: 05/16/2016] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND AND AIMS Neutrophil to lymphocyte ratio (NLR) is an inflammatory-based marker. A systematic review and meta-analysis was performed to explore the prognostic role of NLR in patients with hepatocellular carcinoma (HCC). RESULTS Overall, 598 papers were identified, of which 90 papers including 20,475 HCC patients were finally included. Low baseline NLR was significantly associated with better overall survival (HR = 1.80, 95% CI: 1.59-2.04, p < 0.00001) and recurrence-free or disease-free survival (HR = 2.23, 95% CI: 1.80-2.76, p < 0.00001). Low post- treatment NLR was significantly associated with better overall survival (HR = 1.90, 95% CI: 1.22-2.94, p = 0.004). Decreased NLR was significantly associated with overall survival (HR = 2.23, 95%CI: 1.83-2.72, p < 0.00001) and recurrence-free or disease-free survival (HR = 2.23, 95% CI: 1.83-2.72, p < 0.00001). The findings from most of subgroup meta-analyses were consistent with those from the overall meta-analyses. MATERIALS AND METHODS All relevant literatures were identified via PubMed, EMBASE, and Cochrane library databases. Hazard ratio (HR) with 95% confidence interval (95%CI) was calculated. Subgroup meta-analyses were performed according to the treatment options, NLR cut-off value ranges, and regions. CONCLUSIONS NLR should be a major prognostic factor for HCC patients. NLR might be further incorporated into the prognostic model of HCC.
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Affiliation(s)
- Xingshun Qi
- Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, Liaoning 110840, China
| | - Jianjun Li
- Department of Radiotherapy, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, China
| | - Han Deng
- Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, Liaoning 110840, China
| | - Hongyu Li
- Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, Liaoning 110840, China
| | - Chunping Su
- Library of Fourth Military Medical University, Xi'an, Shaanxi 710032 China
| | - Xiaozhong Guo
- Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, Liaoning 110840, China
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Li MX, Bi XY, Li ZY, Huang Z, Han Y, Zhou JG, Zhao JJ, Zhang YF, Zhao H, Cai JQ. Prognostic Role of Glasgow Prognostic Score in Patients With Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. Medicine (Baltimore) 2015; 94:e2133. [PMID: 26656342 PMCID: PMC5008487 DOI: 10.1097/md.0000000000002133] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Conflicting results about the prognostic value of Glasgow Prognostic Score (GPS) in hepatocellular carcinoma (HCC) patients have been reported. We searched the available articles and performed the meta-analysis to clarify the predictive value of GPS in HCC patients' outcome.A systematic literature search was conducted using PubMed (Medline), Embase, Cochrane Library, Web of Science, ChinaInfo, and Chinese National Knowledge Infrastructure for all years up to September 2015. Studies analyzing the relationship of GPS and survival outcome were identified. Hazard ratio (HR) with 95% confidence interval (CI) was calculated to assess the risk.A total of 10 studies were finally enrolled in the meta-analysis. The pooled estimates demonstrated a significant relationship between elevated GPS and inferior overall survival in patients with HCC (HR = 2.156, 95% CI: 1.696-2.740, P < 0.001). Patients with increased GPS had a tendency toward shorter progression-free survival (HR = 1.755, 95% CI: 0.943-3.265, P = 0.076). And elevated GPS was found to be significantly associated with advanced Child-Pugh class (odds ratio = 25.979, 95% CI: 6.159-109.573, P < 0.001). The publication bias analysis revealed that there was publication bias in the meta-analysis.Glasgow Prognostic Score may be an independent prognostic factor in patients with HCC. More well-designed studies with adequate follow-up duration are warranted.
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Affiliation(s)
- Mu-Xing Li
- From the Department of Abdominal Surgical Oncology (M-XL, X-YB, Z-YL, ZH, J-GZ, J-JZ, Y-FZ, HZ, J-QC) and Department of Radiofrequency Ablation (YH), Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS and PUMC), Cancer Hospital, Beijing, People's Republic of China
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Gao JJ, Shi ZY, Xia JF, Inagaki Y, Tang W. Sorafenib-based combined molecule targeting in treatment of hepatocellular carcinoma. World J Gastroenterol 2015; 21:12059-12070. [PMID: 26576091 PMCID: PMC4641124 DOI: 10.3748/wjg.v21.i42.12059] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2015] [Revised: 07/28/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023] Open
Abstract
Sorafenib is the only and standard systematic chemotherapy drug for treatment of advanced hepatocellular carcinoma (HCC) at the current stage. Although sorafenib showed survival benefits in large randomized phase III studies, its clinical benefits remain modest and most often consist of temporary tumor stabilization, indicating that more effective first-line treatment regimens or second-line salvage therapies are required. The molecular pathogenesis of HCC is very complex, involving hyperactivated signal transduction pathways such as RAS/RAF/MEK/ERK and PI3K/AKT/mTOR and aberrant expression of molecules such as receptor tyrosine kinases and histone deacetylases. Simultaneous or sequential abrogation of these critical pathways or the functions of these key molecules involved in angiogenesis, proliferation, and apoptosis may yield major improvements in the management of HCC. In this review, we summarize the emerging sorafenib-based combined molecule targeting for HCC treatment and analyze the rationales of these combinations.
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