Development and validation of prognostic nomograms in patients with hepatocellular carcinoma: a population-based study

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. The existing staging system has a limited budget capacity for HCC recurrence. The authors aimed to establish and verify two nomogram models to predict disease-free survival (DFS) and overall survival (OS) in patients with HCC. Methods: Patients diagnosed with HCC between August 2011 and March 2016 were recruited. Data were randomly divided into a training cohort and a validation cohort. Based on univariate and multivariate Cox regression analysis, independent risk factors for DFS and OS were identified, and two nomogram models were established to predict patient survival. Results: Sex, tumor size, Barcelona Clinic Liver Cancer (BCLC) stage, tumor capsule, macrovascular invasion, AST-to-platelet ratio index, AST-to-lymphocyte ratio index, neutrophil–lymphocyte ratio and alpha-fetoprotein (AFP) were used to build the nomogram for DFS, while age, tumor size, BCLC stage, tumor capsule, macrovascular invasion, systemic immune-inflammation index, AST, total bilirubin and AFP were used to build the nomogram for OS. Calibration curves showed good agreement between the nomogram prediction and actual observation. C-indices in both nomograms were significantly higher than BCLC. Conclusion: The two nomograms improved the accuracy of individualized prediction of DFS and OS, which may help doctors screen patients with a high risk of recurrence to formulate individualized treatment plans.

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The prognostic and diagnostic significance of the neutrophil-to-lymphocyte ratio in hepatocellular carcinoma: a prospective controlled study

British Journal of Cancer ◽

10.1038/s41416-021-01445-3 ◽

2021 ◽

Author(s):

Philip J. Johnson ◽

Sofi Dhanaraj ◽

Sarah Berhane ◽

Laura Bonnett ◽

Yuk Ting Ma

Keyword(s):

Hepatocellular Carcinoma ◽

Regression Analysis ◽

Prognostic Factor ◽

Cox Regression ◽

Prognostic Models ◽

Controlled Study ◽

Cox Regression Analysis ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Significant Difference

Abstract Background The neutrophil–lymphocyte ratio (NLR), a presumed measure of the balance between neutrophil-associated pro-tumour inflammation and lymphocyte-dependent antitumour immune function, has been suggested as a prognostic factor for several cancers, including hepatocellular carcinoma (HCC). Methods In this study, a prospectively accrued cohort of 781 patients (493 HCC and 288 chronic liver disease (CLD) without HCC) were followed-up for more than 6 years. NLR levels between HCC and CLD patients were compared, and the effect of baseline NLR on overall survival amongst HCC patients was assessed via multivariable Cox regression analysis. Results On entry into the study (‘baseline’), there was no clinically significant difference in the NLR values between CLD and HCC patients. Amongst HCC patients, NLR levels closest to last visit/death were significantly higher compared to baseline. Multivariable Cox regression analysis showed that NLR was an independent prognostic factor, even after adjustment for the HCC stage. Conclusion NLR is a significant independent factor influencing survival in HCC patients, hence offering an additional dimension in prognostic models.

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Development and Validation of Prognostic Nomograms Predicting Recurrence and Survival in Patients with Solitary Hepatocellular Carcinoma Following Curative Liver Resection

10.21203/rs.3.rs-1070685/v1 ◽

2021 ◽

Author(s):

Xinxin Chen ◽

Wenxia Qiu ◽

Xuekun Xie ◽

Zefeng Chen ◽

Zhiwei Han ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Resection ◽

Cox Regression ◽

Disease Free Survival ◽

Clinicopathological Characteristics ◽

Tumor Diameter ◽

Cox Regression Analysis ◽

Tumor Capsule ◽

Calibration Curves ◽

Solitary Hepatocellular Carcinoma

Abstract Background: This work was designed to establish and verify our nomograms integrating clinicopathological characteristics with hematological biomarkers to predict both disease-free survival (DFS) and overall survival (OS) in solitary hepatocellular carcinoma (HCC) patients following hepatectomy.Methods: We scrutinized the data retrospectively from 414 patients with a clinicopathological diagnosis of solitary HCC from Guangxi Medical University Cancer Hospital (Nanning, China) between January 2004 and December 2012. Following the random separation of the samples in a 7:3 ratio into the training set and validation set, the former set was assessed by Cox regression analysis to develop two nomograms to predict the 1-year and 3-year DFS and OS (3-years and 5-years). This was followed by discrimination and calibration estimation employing Harrell’s C-index (C-index) and calibration curves, while the internal validation was also assessed.Results: In the training cohort, the tumor diameter, tumor capsule, macrovascular invasion, and alpha-fetoprotein (AFP) were included in the DFS nomogram. Age, tumor diameter, tumor capsule, macrovascular invasion, microvascular invasion, and aspartate aminotransferase (AST) were included in the OS nomogram. The C-index was 0.691 (95% CI: 0.644-0.738) for the DFS-nomogram and 0.713 (95% CI: 0.670-0.756) for the OS-nomogram. The survival probability calibration curves displayed a fine agreement between the predicted and observed ranges in both data sets. Conclusion: Our nomograms combined clinicopathological features with hematological biomarkers to emerge effective in predicting the DFS and OS in solitary HCC patients following curative liver resection. Therefore, the potential utility of our nomograms for guiding individualized treatment clinically and monitor the recurrence monitoring in these patients.

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Neutrophil-Lymphocyte Ratio and Circulating Tumor Cells Counts Predict Prognosis in Gastrointestinal Cancer Patients

Frontiers in Oncology ◽

10.3389/fonc.2021.710704 ◽

2021 ◽

Vol 11 ◽

Author(s):

Chengcheng Qian ◽

Renjie Cai ◽

Wenying Zhang ◽

Jiongyi Wang ◽

Xiaohua Hu ◽

...

Keyword(s):

Tumor Cells ◽

Circulating Tumor Cells ◽

Gastrointestinal Cancer ◽

Cox Regression ◽

Disease Free Survival ◽

Tumor Location ◽

Cox Regression Analysis ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Related Data

PurposeThe purpose of this study is to explore the prognostic value of associating pre-treatment neutrophil–lymphocyte ratio (NLR) with circulating tumor cells counts (CTCs) in patients with gastrointestinal cancer.Materials and MethodsWe collected the related data of 72 patients with gastric cancer (GC) and colorectal cancer (CRC) who received different therapies from August 2016 to October 2020, including age, gender, primary tumor location, TNM stage, tumor-differentiation, NLR, CTCs, disease-free survival (DFS) and overall survival (OS). We chose the optimal cut-off value of NLR >3.21 or NLR ≤3.21 and CTC >1 or CTC ≤1 by obtaining receiver operating characteristic (ROC) curve. The Kaplan–Meier survival analysis and Cox regression analysis were used to analyze DFS and OS. To clarify the role of the combination of NLR and CTCs counts in predicting the prognosis, we analyzed the DFS and OS when associated NLR and CTCs counts.ResultsA high NLR (>3.21) was associated with shorter DFS (P <0.0001) and OS (P <0.0001). Patients with high CTCs level (>1) had shorter DFS (P = 0.001) and OS (P = 0.0007) than patients with low CTCs level. Furthermore, patients who had both higher NLR and higher CTCs counts had obvious shorter DFS (P <0.0001) and OS (P <0.0001).ConclusionsPatients with higher NLR and more CTCs respectively tended to have poor prognosis with shorter DFS and OS, which might be regarded as predictors of gastrointestinal cancer. In particular, associating NLR and CTCs counts might be a reliable predictor in patients with gastrointestinal cancer.

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Short term survival of critically ill COVID-19 Egyptian patients on assisted ventilation treated by either Dexamethasone or Tocilizumab

Scientific Reports ◽

10.1038/s41598-021-88086-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Alaa Rashad ◽

Sherif Mousa ◽

Hanaa Nafady-Hego ◽

Asmaa Nafady ◽

Hamed Elgendy

Keyword(s):

Critically Ill ◽

Cox Regression ◽

Ferritin Level ◽

Short Term ◽

Term Survival ◽

Cox Regression Analysis ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Dexamethasone Group ◽

Short Term Survival

AbstractTocilizumab (TCZ) and Dexamethasone are used for the treatment of critically ill COVID-19 patients. We compared the short-term survival of critically ill COVID-19 patients treated with either TCZ or Dexamethasone. 109 critically ill COVID-19 patients randomly assigned to either TCZ therapy (46 patients) or pulse Dexamethasone therapy (63 patients). Age, sex, neutrophil/ lymphocyte ratio, D-dimer, ferritin level, and CT chest pattern were comparable between groups. Kaplan–Meier survival analysis showed better survival in Dexamethasone group compared with TCZ (P = 0.002), patients didn’t need vasopressor at admission (P < 0.0001), patients on non-invasive ventilation compared to patients on mechanical ventilation (P<0.0001 ), and in patients with ground glass pattern in CT chest (P<0.0001 ) compared with those who have consolidation. Cox regression analysis showed that, TCZ therapy (HR = 2.162, 95% CI, 1.144–4.087, P <0.0001) compared with Dexamethasone group, higher neutrophil/Lymphocyte ratio (HR = 2.40, CI, 1.351–4.185, P = 0.003), lower PaO2/FiO2, 2 days after treatment, (HR = 1.147, 95% CI, 1.002–1.624, P < 0.0001) independently predicted higher probability of mortality. Dexamethasone showed better survival in severe COVID-19 compared to TCZ. Considering the risk factors mentioned here is crucial when dealing with severe COVID-19 cases.Clinical trial registration No clinicalTrials.gov: Nal protocol approved by Hospital Authorities, for data collection and for participation in CT04519385 (19/08/2020).

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Combination of Tertiary Lymphoid Structure and Neutrophil-to-Lymphocyte Ratio Predicts Survival in Patients With Hepatocellular Carcinoma

Frontiers in Immunology ◽

10.3389/fimmu.2021.788640 ◽

2022 ◽

Vol 12 ◽

Author(s):

Shaodi Wen ◽

Yuzhong Chen ◽

Chupeng Hu ◽

Xiaoyue Du ◽

Jingwei Xia ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Systemic Inflammation ◽

Cox Regression ◽

Primary Liver Cancer ◽

Paraffin Section ◽

Neutrophil To Lymphocyte Ratio ◽

Survival Prediction ◽

Cox Regression Analysis ◽

Lymphocyte Ratio ◽

Inflammation Parameters

BackgroundHepatocellular 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 MethodsWe 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.ResultsWe 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.ConclusionThe 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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Efficacy of Postoperative FOLFOX Versus XELOX Chemotherapy for Gastric Cancer and Prognostic Value of Platelet–Lymphocyte Ratio in Patients Receiving XELOX

Frontiers in Oncology ◽

10.3389/fonc.2020.584772 ◽

2020 ◽

Vol 10 ◽

Author(s):

Xin Yin ◽

Tianyi Fang ◽

Yimin Wang ◽

Chunfeng Li ◽

Yufei Wang ◽

...

Keyword(s):

Gastric Cancer ◽

Tumor Size ◽

Prognostic Value ◽

Cox Regression ◽

Postoperative Chemotherapy ◽

Chinese Patients ◽

Cox Regression Analysis ◽

Lymphocyte Ratio ◽

Platelet Lymphocyte Ratio ◽

Ptnm Stage

BackgroundSurgery combined with postoperative chemotherapy is an effective method for treating patients with gastric cancer (GC) in Asia. The important roles of systemic inflammatory response in chemotherapy have been gradually verified. The purpose of this study was to assess the difference in clinical effectiveness of FOLFOX (oxaliplatin + leucovorin + 5-fluorouracil) and XELOX (oxaliplatin + capecitabine), and the prognostic value of postoperative platelet–lymphocyte ratio (PLR) in the XELOX group.MethodsPatients who received radical gastrectomy combined with postoperative chemotherapy between 2004 and 2014 were consecutively selected into the FOLFOX and XELOX groups. Group bias was reduced through propensity score matching, which resulted in 278 patients in each group. Cut-off values of systemic immune inflammation (SII) score and PLR were obtained by receiver operating characteristic curve. Kaplan–Meier and Log-rank tests were used to analyze overall survival. The chi-square test was used to analyze the association between clinical characteristics and inflammatory indexes. Univariate and multivariate analyses based on Cox regression analysis showed independent risk factors for prognosis. The nomogram was made by R studio.ResultsPatients receiving XELOX postoperative chemotherapy had better survival than those receiving FOLFOX (P < 0.001), especially for stage III GC (P = 0.002). Preoperative SII was an independent risk factor for prognosis in the FOLFOX group, and PLR of the second postoperative chemotherapy regimen in the XELOX group, combined with tumor size and pTNM stage, could construct a nomogram for evaluating recurrence and prognosis.ConclusionXELOX is better than FOLFOX for treatment of GC in Chinese patients, and a nomogram constructed by PLR, tumor size and pTNM stage can predict recurrence and prognosis.

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Predictive role of peritumoral CD3+ infiltration and neutrophil to lymphocyte ratio on overall survial in pateints affected by colorectal liver metastases treated with chemotherapy and surgery.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.5_suppl.27 ◽

2018 ◽

Vol 36 (5_suppl) ◽

pp. 27-27

Author(s):

Matteo Cimino ◽

Matteo Donadon ◽

Domenico Mavilio ◽

Luca Di Tommaso ◽

Massimo Roncalli ◽

...

Keyword(s):

Liver Metastases ◽

Colorectal Liver Metastases ◽

Protective Factor ◽

Cox Regression ◽

Absolute Lymphocyte Count ◽

Cox Regression Analysis ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Markers Of Inflammation

27 Background: Systemic and local inflammation plays an important role in many cancers and colorectal liver metastases (CRLM). While the role of local immune response mediated by CD3+ tumour infiltrating lymphocyte is well established new evidence on systemic inflammation and cancer such as neutrophil–lymphocyte ratio (NLR) are emerging. The aim of the study is to associate these two markers of inflammation to predict overall survival (OS) in patients affected by CRLM. Methods: From January 2006 to January 2013 128 consecutive patients affected by CRLM treated with chemotherapy and surgery were included in the study. CD3+ peritumoral infiltration was defined as the ratio of intra-tumoural\invasive-margin CD3+ infiltration evaluated with immunohistochemistry on CRLM tumor slides. NLR was calculated as neutrophil absolute count divided by the absolute lymphocyte count on blood sample. ROC curves were used to calculate a cut-off for each bio-markers related to OS . Associating the bio-markers two risk groups were determined: low risk (LRG) two protective bio-markers; high risk (HRG) no protective bio-markers. Results: After a median follow-up of 45 months, median OS was 44 months.Twenty-nine patients (22.6%) belong to the LRG whereas 99 patients (77,4) belong to HRG. Adjusted Cox regression analysis showed a worse OS for HRG patients (HR 2.74 p = 0.003 95%CI 1.40-5.37). Median OS was 80.8 vs 42.5 months for LRG vs HRG respectively. Conclusions: High CD3+ peritumoural infiltration associated with low NRL are two protective factor on OS for patients affected by CRLM.

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Coexpression of PDGFR-Alpha, PDGFR-Beta and VEGF as a Prognostic Factor in Patients with Hepatocellular Carcinoma

The International Journal of Biological Markers ◽

10.5301/jbm.2011.8322 ◽

2011 ◽

Vol 26 (2) ◽

pp. 108-116 ◽

Cited By ~ 15

Author(s):

Li Chen ◽

Yan Shi ◽

Cheng-ying Jiang ◽

Li-xin Wei ◽

Ya-li Lv ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Growth Factor ◽

Proportional Hazards Model ◽

Cox Regression ◽

Univariate Analysis ◽

Prognostic Significance ◽

Disease Free Survival ◽

Hazard Ratio ◽

Cox Proportional Hazards Model ◽

Cox Regression Analysis

Aims To evaluate the prognostic value of vascular endothelial growth factor (VEGF), platelet-derived growth factor receptor-alpha (PDGFR-α) and beta (PDGFR-β) expression in patients with hepatocellular carcinoma (HCC). Methods The expression of PDGFR-α, PDGFR-β and VEGF in 63 HCC patients who underwent curative resection was examined by immunohistochemistry (IHC). The correlations between the expression of these biomarkers and the clinicopathological characteristics were analyzed. Patient survival was analyzed by univariate analysis and Cox proportional hazards model. Results Univariate survival analysis showed that PDGFR-α or PDGFR-β overexpression was of no prognostic significance in predicting disease-free survival (DFS) and overall survival (OS) (p>0.05), while VEGF overexpression and PDGFR-α/PDGFR-β/VEGF coexpression were significantly correlated with worse DFS and poorer OS in HCC patients (P<0.05). More importantly, PDGFR-α/PDGFR-β/VEGF coexpression was an independent prognostic marker for poor survival as indicated by multivariate Cox regression analysis (DFS, hazard ratio 3.122, p=0.001; OS, hazard ratio 4.260, p=0.000). Conclusions Coexpression of PDGFR-α, PDGFR-β and VEGF could be considered an independent prognostic biomarker for predicting DFS and OS in HCC patients. This result could be used to identify patients at a higher risk of tumor recurrence and poor prognosis, and help to select therapeutic schemes for the treatment of HCC.

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Commentary on: Nomograms based on inflammatory biomarkers for predicting tumor grade and microvascular invasion in stage I/II hepatocellular carcinoma

Bioscience Reports ◽

10.1042/bsr20190683 ◽

2019 ◽

Vol 39 (10) ◽

Author(s):

Liang Xiao ◽

Furong Zeng ◽

Guangtong Deng

Keyword(s):

Hepatocellular Carcinoma ◽

Multivariate Analysis ◽

Tumor Size ◽

Tumor Grade ◽

Microvascular Invasion ◽

Stage I ◽

Inflammatory Biomarkers ◽

Independent Dataset ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio

Abstract Some doubts were generated during the reading of nomograms based on inflammatory biomarkers for preoperatively predicting tumor grade and microvascular invasion in stage I/II hepatocellular carcinoma (HCC). We would like to highlight and discuss with authors. First, neutrophil-lymphocyte ratio (NLR) and derived NLR (dNLR) should not be entered into multivariate analysis simultaneously. Second, authors should clarify how the cutoffs of these variables including lymphocyte-monocyte ratio (LMR), dNLR, age and tumor size were set. We insist that the type of variables should be consistent when we carry out the analysis and establish the nomogram. Last, we have to point out that Li et al.’s (Biosci. Rep. (2018), 38) study failed to validate nomograms using an independent dataset.

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PD-L1+NEUT, Foxp3+Treg, and NLR as New Prognostic Marker with Low Survival Benefits Value in Hepatocellular Carcinoma

Technology in Cancer Research & Treatment ◽

10.1177/15330338211045820 ◽

2021 ◽

Vol 20 ◽

pp. 153303382110458

Author(s):

Lin Zhou ◽

Jing Wang ◽

Shao-cheng Lyu ◽

Li-chao Pan ◽

Xian-jie Shi ◽

...

Keyword(s):

Risk Factors ◽

Hepatocellular Carcinoma ◽

Peripheral Blood ◽

Cox Regression ◽

Disease Free Survival ◽

Rank Test ◽

Cancer Tissue ◽

Cox Regression Analysis ◽

Poorly Differentiated ◽

Independent Risk Factors

Background: This presented study was aimed to evaluate the diagnostic and prognostic value of PD-L1+Neutrophils (PD-L1+NEUT) and neutrophil to lymphocyte ratio (NLR) based on our previous experience of Foxp3+Treg in transplantation. Methods: the NLR cutoff value of 1.79 was used to include 136 cases from the 204 patients with hepatocellular carcinoma (HCC) confirmed by clinical pathology, which were divided into highly-moderately and poorly differentiated HCC groups. The expressions of PD-L1+NEUT and Foxp3+Treg in peripheral blood and cancer tissue were detected with flow cytometry, meanwhile, PD-L1 and Foxp3 expressed in carcinoma and para-carcinoma tissues were marked by immunohistochemistry. Survival rates, including overall survival and disease-free survival, were calculated by the Kaplan–Meier curve and evaluated with the log-rank test. Finally, Cox risk regression model was used to analyze the independent risk factors for prognostic survival. Results: The level of PD-L1+NEUT, Foxp3+Treg, and NLR in peripheral blood of patients with poorly differentiated HCC were significantly increased (all P < .001). Both PD-L1+NEUT and NLR were positively correlated with Foxp3+Treg ( r = 0.479, P = .0017; r = 0.58, P < .0001). The level of PD-L1+NEUT and Foxp3+Treg as well as PD-L1 and Foxp3 in cancer tissue and patients with poorly differentiated HCC were obviously increased (all P < .01), respectively. Cox regression analysis indicated that PD-L1+NEUT, NLR, and Foxp3+Treg were independent risk factors for the prognosis ( P = .000, .000, .006) with a RR and 95%CI of 2.704-(2.155-3.393), 3.139-(2.361-4.173), 1.409-(1.105-1.798), respectively. Conclusion: PD-L1+NEUT, NLR, and Foxp3+Treg are independent risk factors for prognosis which maybe new marker of lower survival benefits.

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