High neutrophil-to-lymphocyte ratio as an independent adverse prognostic factor in racial minorities with hepatocellular carcinoma.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 218-218
Author(s):  
Santiago Thibaud ◽  
Santiago Aparo ◽  
Jennifer W. Chuy ◽  
Andreas Kaubisch

218 Background: An elevated neutrophil-to-lymphocyte ratio (NLR) has been shown to portend poor prognosis in various types of cancer, including hepatocellular carcinoma (HCC). However, studies that evaluated the prognostic significance of NLR did not include large numbers of Blacks and Hispanics. This single-center, retrospective study conducted on a large, racially diverse cohort explores the utility of NLR in predicting outcomes in minority populations. Methods: We identified patients (pts) diagnosed with HCC at our institution between the years 2000 and 2016. We calculated NLR at the time of diagnosis and divided pts into two groups: high NLR (NLR > 3) and low NLR (NLR ≤3). Demographics, clinical characteristics, MELD/MELD-Na scores, ALBI scores and AFP levels were collected. Survival analysis was conducted using the Kaplan-Meier method. Cox proportional-hazards model was used for multivariate analysis. Results: 751 pts with HCC were included in this study. 542 (72%) were male. Median age was 61 years. 43% were Hispanic, 33% Black, 22% White and 2% Other. NLR was high in 246 pts (32.7%, mean 6.0 ± 3.8) and low in 505 pts (67.2%, mean 1.69 ± 0.7). Overall survival (OS) was significantly lower in the high NLR group (median survival 25.4 vs 49.6 months, HR 1.75, 95% CI 1.41-2.17, P < 0.01). Subgroup analysis showed differences remained significant in the Hispanic group (n = 259, HR 1.93, 95% CI 1.30-2.86, P < 0.01) and the Black group (n = 194, HR 1.99, 95% CI 1.28-3.09, P < 0.01). The high NLR group had significantly higher MELD scores (mean 12.1 ± 5.0 vs 10.1 ± 3.8, P < 0.01), MELD-Na scores (13.9 ± 5.6 vs 11.3 ± 4.4, P < 0.01), ALBI scores (-2.05 ± 0.7 vs -2.28 ± 0.6, P < 0.01) and AFP levels (median 28.9 vs 46.9, P = 0.02). An NLR > 3 on multivariate analysis remained significantly associated with worse OS (HR 1.31; 95% CI 1.03-1.68; P = 0.02) after adjusting for age, gender, AFP and MELD-Na. Conclusions: NLR > 3 at the time of diagnosis had a strong correlation with poor OS in a large, racially diverse cohort of pts with HCC. This correlation held true for both Hispanic and Black patients, who have been previously underrepresented in similar studies. Our findings support the utility of NLR as a prognostic tool in HCC.

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1130
Author(s):  
Shu-Yein Ho ◽  
Chia-Yang Hsu ◽  
Po-Hong Liu ◽  
Chih-Chieh Ko ◽  
Yi-Hsiang Huang ◽  
...  

Renal insufficiency (RI) is commonly seen in patients with hepatocellular carcinoma (HCC). The prognostic role of albumin-bilirubin (ALBI) grade in this special setting is unclear. We aimed to investigate the role of ALBI grade associated with the impact of RI on HCC. A prospective cohort of 3690 HCC patients between 2002 and 2016 were retrospectively analyzed. The Kaplan–Meier method and multivariate Cox proportional hazards model were used to determine survival and independent prognostic predictors. Of all patients, RI was an independent predictor associated with decreased survival. In multivariate Cox analysis for patients with RI, α-fetoprotein level ≥20 ng/mL, tumor size >3 cm, vascular invasion, distant metastasis, presence of ascites, performance status 1–2, performance status 3–4, and ALBI grade 2 and grade 3 were independent predictors of decreased survival (all p < 0.05). In subgroup analysis of patients with RI undergoing curative and non-curative treatments, the ALBI grade remained a significant prognostic predictor associated with decreased survival (p < 0.001). In summary, HCC patients with RI have decreased survival compared to those without RI. The ALBI grade can discriminate the survival in patients with RI independent of treatment strategy and is a feasible prognostic tool in this special patient population.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 563-563
Author(s):  
Julia Alcaide ◽  
Antonio Rueda ◽  
Isabel Rodrigo ◽  
Teresa Tellez ◽  
Rafael Funez ◽  
...  

563 Background: Increased CLU is involved in malignant progression and anticlusterin treatment with antisense oligonucleotides enhances apoptosis induced by several citotoxics. However, clinical significance of CLU expression in human CRCs has been scarcely studied. We investigated whether changes in CLU could be related to carcinogenesis and survival (sv) of CRC patients (pts). Methods: Formalin-fixed and paraffin-embedded specimens were examined from 31 adenomas and 103 CRCs resected at Costa del Sol Hospital. The study was approved by Research Ethics Committee. Immunohistochemistry using monoclonal anti-α chain clusterin antibody (Upstate-Millipore, Watford, England) was performed, following standard staining procedure. CLU was scored as negative (CLU–) (no staining) or positive (CLU +) (>10% of tumor cells with strong staining). Cytoplasmic CLU in tumors was evaluated for cancer cells only, and in normal mucosa for epithelial cells only. Sv curves were calculated and plotted according to Kaplan-Meier method. Predictors that were significant at p<0.10 in univariate analysis, were entered into a Cox proportional hazards model for multivariate analysis, remaining significant at p<0.05. Results: Median follow-up was 54 months. Median age was 70 years (45-91). TNM stage distribution was: I (13%), II (48%), III (25%) and IV (14%). Epithelial normal cells were always CLU-, but 16% (5/31) of adenomas was CLU+ and this percentage increased in CRCs (30%, 31/103). Positive staining always presented an apical cytoplasmic pattern. Recurrence was more frequent in CLU+ (61%,19/ 31) than in CLU- tumors (37%, 27/72) and CLU was significantly associated with lower disease-free survival (DFS) (p<0.05). In multivariate analysis, CLU and stage remained significant independent prognostic factors for DFS (Table). Conclusions: CLU has a role in colon carcinogenesis and prognostic value. CLU is associated with decreased DFS among pts with CRCs. These findings have important implications for identifying CRC pts with more aggressive tumors who may benefit from targeted therapy against clusterin. [Table: see text]


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15729-e15729
Author(s):  
Michael Shusterman ◽  
Erin Jou ◽  
Andreas Kaubisch ◽  
Jennifer W. Chuy ◽  
Lakshmi Rajdev ◽  
...  

e15729 Background: The neutrophil to lymphocyte ratio (NLR), a marker of systemic inflammatory response, has been suggested as a prognostic marker in patients with pancreatic adenocarcinoma (PAC). Black and Hispanic patients have been underrepresented in studies evaluating the significance of NLR in PAC. We investigated the prognostic significance of NLR in patients with advanced PAC treated at the Montefiore-Einstein Center for Cancer Care (MECCC) in the Bronx, NY. Methods: We included patients who were chemotherapy naive and treated for unresectable or metastatic PAC at MECCC between 2006 and 2015. Demographics, clinical characteristics and treatment data were collected. Overall survival was determined by the Kaplan-Meier method and Cox proportional-hazards models were built to assess survival differences adjusting for clinically relevant and statistically significant variables. Results: 201 patients were included in the study. Median age was 65 (range 32, 90). 52% were male. 41 were White (19%), 71 Black (33%), 71 Hispanic (33%), and 33 Other (15.3%). 66 (30.6%) had unresectable disease and 135 (62.5%) metastatic disease. An NLR ≥ 4 was associated with a worse OS compared to an NLR ≤ 4 (median 10 vs. 16.4 months; HR 1.895; 95% CI 1.390, 2.585; P < 0.0001). Predictors of worse OS on univariate analysis were ever smoker status (HR 1.365; P = 0.05), metastatic disease (HR 1.736; P = 0.001), and albumin ≤ 3.5 g/dL (HR 2.558; P< 0.0001). An NLR ≥ 4 on multivariate analysis remained significantly associated with worse OS (HR 1.665; 95% CI 1.188, 2.334; P = 0.003) after adjusting for age, gender, ever smoker status, metastatic disease, and albumin. Conclusions: In a cohort with significant minority patient representation, an NLR ≥ 4 was associated with significantly worse overall survival in patients with advanced pancreatic cancer. An elevated NLR in advanced PAC may be an important independent predictor to risk stratify patients and predict poor OS in future analyses.


2017 ◽  
Vol 42 (2) ◽  
pp. 660-672 ◽  
Author(s):  
Mao-Wei Cheng ◽  
Ze-Tian Shen ◽  
Gu-Yu Hu ◽  
Li-Guo Luo

Background: Previously, microRNA (miR)-7 has been reported to function as a tumor suppressor in human cancers, but the correlations of miR-7 expression with prognosis and cisplatin (CDDP) resistance in lung adenocarcinoma (LA) are unclear. Here, our aim is to determine the prognostic significance of miR-7 and its roles in the regulation of CDDP resistance in LA. Methods: Quantitative real-time PCR (qRT-PCR) assay was performed to determine miR-7 expression in 108 paired of LA tissues and analyze its correlations with clinicopathological factors of patients. The patient survival data were collected retrospectively by Kaplan-Meier analyses, and multivariate analysis was performed using the Cox proportional hazards model to determine the prognostic significance of miR-7 expression. The effects of miR-7 expression on the chemosensitivity of LA cells to CDDP and its possible mechanisms were evaluated by MTT, flow cytometry, Western blot and luciferase assays. Results: It was observed that the relative expression level of miR-7 in LA tissues was significantly lower than that in the adjacent normal tissues and low miR-7 expression level was closely associated with poorer tumor differentiation, advanced pathological T-factor, higher incidence of lymph node metastasis and advanced p-TNM stage. Also, patients with low miR-7 expression showed a shorter overall survival than those with high miR-7 expression, and multivariate analysis indicated that status of miR-7 expression was an independent molecular biomarker for predicting the overall survival (OS) of LA patients. In addition, upregulation of miR-7 increases the sensitivity of LA cells to CDDP via induction of apoptosis by targeting Bcl-2. Conclusions: Our finding for the first time demonstrates that low miR-7 expression may be an independent poor prognostic factor and targeting miR-7 may be a potential strategy for the reversal of CDDP resistance in LA.


2018 ◽  
Vol 46 (6) ◽  
pp. 2335-2346 ◽  
Author(s):  
Guangyan Zhangyuan ◽  
Yin Yin ◽  
Wenjie Zhang ◽  
WeiWei Yu ◽  
Kangpeng Jin ◽  
...  

Background/Aims: During the occurrence and progression of hepatocellular carcinoma (HCC), phosphotyrosine phosphatases (PTPs) are usually described as tumor suppressors or proto-oncogenes, and to some degree are correlated with the prognosis of HCC. Methods: A total of 321 patients from the Cancer Genome Atlas (TCGA) database and 180 patients from our validated cohort with hepatocellular carcinoma were recruited in this study. Kaplan-Meier, univariate and multivariate Cox proportional hazards model were used to evaluate the risk factors for survival. Quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) were applied to detect the expression levels of PTP genes. Results: After screening the data of TCGA, we identified five PTPs as HCC overall survival related PTP genes, among which only three (PTPN12, PTPRN, PTPN18) exhibited differential expression levels in our 180 paired HCC and adjacent tissues (P< 0.001). Further analysis revealed that expression of PTPN18 was positively, but PTPRN was negatively associated with prognosis of HCC both in TCGA cohort and our own cohort. As to PTPN12, results turned out to be opposite according to HBV status. In detail, higher expression of PTPN12 was associated with better outcome in HBV group but worse prognosis in Non-HBV group. Conclusion: Our results suggested that PTPN12, PTPRN and PTPN18 were independent prognostic factors in HCC.


1999 ◽  
Vol 17 (9) ◽  
pp. 2721-2721 ◽  
Author(s):  
George Sato ◽  
Yasuo Saijo ◽  
Bine Uchiyama ◽  
Nobuko Kumano ◽  
Shun-ichi Sugawara ◽  
...  

PURPOSE: In this study we investigated the prognostic significance of proliferation-associated nucleolar protein p120 in primary resected lung adenocarcinoma because it reflects tumor growth fractions in vitro. PATIENTS AND METHODS: Expression levels of p120 in tumors were assessed by immunohistochemistry in 74 patients who underwent radical resection. With clinical follow-up data, the prognostic significance of p120 calculated by labeling indices was evaluated using the Cox proportional hazards model. RESULTS: p120 protein was clearly detected in nucleoli of adenocarcinoma cells. Its expression levels widely varied in each sample from 8.5% to 67.2%, with a mean ± SD of 35.2% ± 15.1%. No significant correlation was found between expression levels of p120 and clinicopathologic factors. However, the expression levels of p120 were negatively correlated with the tumor doubling time calculated with retrospective chest roentgenograms. Using a cutoff value of 35% in the labeling index of p120, patients with high expression of p120 experienced early recurrence and shorter survival compared with those who had low expression of p120. Multivariate analysis showed that p120 served as an independent, as well as the strongest, prognostic factor for resected lung adenocarcinoma. CONCLUSION: This report provides the first evidence that expression levels of p120 in tumor tissues can be used as an independent and powerful prognostic marker for resected lung adenocarcinoma.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Ke Shi ◽  
Yao Liu ◽  
Xiaojing Wang ◽  
Yuxin Li ◽  
Qun Zhang ◽  
...  

Aim. Fuzhenghuayu (FZHY) capsule can inhibit the progression of cirrhosis. This study explored whether FZHY can reduce the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis B-caused cirrhosis (HBC) undergoing antiviral therapy. Methods. A retrospective review of 842 patients with HBC between 2011 and 2015 was performed, including 270 treated with FZHY combined with nucleos (t) ide analogues (NAs) and 572 with NAs alone. The incidence of HCC was compared between the FZHY (n = 259) and control (n = 259) groups using 1 : 1 propensity score (PS) matching. The incidence of HCC in patients with HBC with different Child-Turcotte-Pugh (CTP) classifications and Toronto HCC risk index (THRI) scores was analyzed using Kaplan–Meier curves. Results. The 5-year cumulative incidence of HCC before and after PS matching was 151 (17.9%) and 86 (16.6%), respectively. In PS-matched samples, the multivariate Cox proportional-hazards model indicated that the FZHY group demonstrated a significantly lower risk for HCC than the control group (adjusted hazard ratio [aHR] = 0.32, 95% CI 0.19–0.53 P < 0.001 ). The risk of HCC diminished with increased duration of FZHY use. The stratified analysis revealed that the FZHY group, regardless of CTP classification, benefited significantly from FZHY therapy. Patients in the medium- and high-THRI risk groups were the dominant population for FZHY. Conclusions. FZHY combined with NAs was associated with a significantly lower risk of HCC than NAs alone in patients with HBC, which supports the integration of FZHY with antiviral treatment into clinical practice.


Liver Cancer ◽  
2021 ◽  
pp. 1-10
Author(s):  
Masatoshi Kudo ◽  
Richard S. Finn ◽  
Manabu Morimoto ◽  
Kun-Ming Rau ◽  
Masafumi Ikeda ◽  
...  

<b><i>Background:</i></b> Intermediate-stage hepatocellular carcinoma (HCC), as defined by Barcelona Clinic Liver Cancer (BCLC) stage B, is heterogeneous in terms of liver function and tumor burden. REACH and REACH-2 investigated ramucirumab in patients with HCC after prior sorafenib, with REACH-2 enrolling only patients with baseline α-fetoprotein (AFP) ≥400 ng/mL. An exploratory analysis of outcomes by BCLC stage was performed. <b><i>Methods:</i></b> A pooled meta-analysis of independent patient data (stratified by study) from REACH (AFP ≥ 400 ng/mL) and REACH-2 was performed. All patients had Child-Pugh A, Eastern Cooperative Oncology Group performance status 0–1, prior sorafenib treatment, and either HCC BCLC stage B (refractory/not amenable to locoregional therapy) or BCLC stage C. Patients were randomized to ramucirumab 8 mg/kg or placebo every 2 weeks. Median overall survival (OS) and progression-free survival were estimated by the Kaplan-Meier method. Treatment effects in BCLC stage B and C were evaluated by Cox proportional-hazards model; prognosis of BCLC staging for OS was evaluated by multivariate Cox proportional-hazards model. Tumor responses were evaluated according to Response Evaluation in Solid Tumors v1.1. Liver function was assessed with albumin-bilirubin score. <b><i>Results:</i></b> Baseline characteristics were generally balanced between treatment arms in each BCLC stage. BCLC staging trended as an independent prognostic factor for OS (B vs. C; hazard ratio [HR] 0.756 [95% CI 0.546–1.046]). Consistent treatment benefit was observed for ramucirumab versus placebo across BCLC stages. Median OS for ramucirumab versus placebo was 13.7 versus 8.2 months; HR (95%): 0.43 (0.23–0.83) and 7.7 versus 4.8 months; HR (95%): 0.72 (0.59–0.89) for BCLC stage B and C, respectively. Adverse events (AEs) were consistent with observations from both studies; hypertension was the most frequent grade ≥3 AE. Liver function was preserved throughout the study and similar between treatment arms in both BCLC stages. <b><i>Conclusions:</i></b> Ramucirumab provided a better survival benefit irrespective of BCLC stage and was well tolerated without compromising liver function during treatment.


2021 ◽  
Vol 19 (3) ◽  
pp. 285-293
Author(s):  
Andrew M. Moon ◽  
Hanna K. Sanoff ◽  
YunKyung Chang ◽  
Jennifer L. Lund ◽  
A. Sidney Barritt ◽  
...  

Background: Early treatment of hepatocellular carcinoma (HCC) is associated with improved survival, but many patients with HCC do not receive therapy. We aimed to examine factors associated with HCC treatment and survival among incident patients with HCC in a statewide cancer registry. Materials and Methods: All patients with HCC from 2003 through 2013 were identified in the North Carolina cancer registry. These patients were linked to insurance claims from Medicare, Medicaid, and large private insurers in North Carolina. Associations between prespecified covariates and more advanced HCC stage at diagnosis (ie, multifocal cancer), care at a liver transplant center, and provision of HCC treatment were examined using multivariate logistic regression. A Cox proportional hazards model was developed to assess the association between these factors and survival. Results: Of 1,809 patients with HCC, 53% were seen at a transplant center <90 days from diagnosis, with lower odds among those who were Black (adjusted odds ratio [aOR], 0.54; 95% CI, 0.39–0.74), had Medicare insurance (aOR, 0.35; 95% CI, 0.21–0.59), had Medicaid insurance (aOR, 0.46; 95% CI, 0.28–0.77), and lived in a rural area; odds of transplant center visits were higher among those who had prediagnosis alpha fetoprotein screening (aOR, 1.74; 95% CI, 1.35–2.23) and PCP and gastroenterology care (aOR, 1.66; 95% CI, 1.27–2.18). Treatment was more likely among patients who had prediagnosis gastroenterology care (aOR, 1.68; 95% CI, 0.98–2.86) and transplant center visits (aOR, 2.42; 95% CI, 1.74–3.36). Survival was strongly associated with age, cancer stage, cirrhosis complications, and receipt of HCC treatment. Individuals with Medicare (adjusted hazard ratio [aHR], 1.58; 95% CI, 1.20–2.09) and Medicaid insurance (aHR, 1.55; 95% CI, 1.17–2.05) had shorter survival than those with private insurance. Conclusions: In this population-based cohort of patients with HCC, Medicare/Medicaid insurance, rural residence, and Black race were associated with lower provision of HCC treatment and poorer survival. Efforts should be made to improve access to care for these vulnerable populations.


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