scholarly journals Prognostic Role of Albumin, Bilirubin, and ALBI Scores: Analysis of 1000 Patients with Hepatocellular Carcinoma Undergoing Radioembolization

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 879 ◽  
Author(s):  
Mark Antkowiak ◽  
Ahmed Gabr ◽  
Arighno Das ◽  
Rehan Ali ◽  
Laura Kulik ◽  
...  

Introduction: We compared the efficacy of the ALBI (albumin–bilirubin) score to the established Child–Pugh (CP) grade in hepatocellular carcinoma (HCC) patients treated with yttrium-90 radioembolization (Y90). We further assessed the individual contributions of albumin and bilirubin to survival prediction. Methods: 1000 consecutive HCC patients treated with Y90 were included. Overall survival (OS) was assessed using Kaplan Meier analysis. Sub-stratification analyses were performed using CP and ALBI and in subgroups determined by United Network for Organ Sharing (UNOS) or Barcelona Clinic Liver Cancer (BCLC) staging. The independent impact (hazard ratio (HR)) of ALBI, CP, albumin, and bilirubin on survival was assessed using Cox proportional hazards analysis. Results: Median OS for ALBI 1, 2, and 3 grades was 46.7, 19.1, and 8.8 months, respectively. The HR for death for ALBI 2 vs. ALBI 1 was 3.39 (1.75–6.57); ALBI 3 vs. ALBI 1 was 7.58 (3.89–14.79); and the c-index was 0.623. Median OS for CP A, B, and C was 21.7, 11.3, and 6.0 months, respectively. The HR for death for CP B vs. CP A was 2.04 (1.71–2.43); CP C vs. CP A was 3.27 (2.08–5.14); and the c-index was 0.616. Stratified OS showed unique prognostic groups identified by ALBI within CP-B and CP-C. Median OS for albumin grades 1, 2, and 3 was 46.0, 17.1, and 9.1 months, respectively. Median OS for bilirubin grades 1, 2, and 3 was 15.6, 21.0, and 5.8 months, respectively. The HR for death for albumin 2 vs. 1 was 2.48 (1.81–3.41); albumin 3 vs. 1 was 4.74 (3.44–6.54); and the c-index was 0.640. The HR for death for bilirubin 2 vs. 1 was 1.09 (0.82–1.44); bilirubin 3 vs. 1 was 2.37 (1.66–3.40); and the c-index was 0.533. Conclusions: ALBI outperforms CP in survival prognosis in Y90 treated patients. On sub-analyses, serum albumin (not bilirubin) appears to be the main driver of survival prediction. Our study supports the prognostic ability of ALBI and may suggest a role of albumin alone as a biomarker for patients with HCC.

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Tong-min Xue ◽  
Li-de Tao ◽  
Miao Zhang ◽  
Jie Zhang ◽  
Xia Liu ◽  
...  

miRNA-20b has been shown to be aberrantly expressed in several tumor types. However, the clinical significance of miRNA-20b in the prognosis of patients with hepatocellular carcinoma (HCC) is poorly understood, and the exact role of miRNA-20b in HCC remains unclear. The aim of the present study was to investigate the association of the expression of miR-20b with clinicopathological characteristics and overall survival of HCC patients analyzed by Kaplan-Meier analysis and Cox proportional hazards regression models. Meanwhile, the HIF-1αand VEGF targets of miR-20b have been confirmed. We found not only miR-20b regulation of HIF-1αand VEGF in normal but also regulation of miR-20b in hypoxia. This mechanism would help the tumor cells adapt to the different environments thus promoting the tumor invasion and development. The whole study suggests that miR-20b, HIF-1α, and VEGF serve as a potential therapeutic agent for hepatocellular carcinoma.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16659-e16659
Author(s):  
Sunyoung S. Lee ◽  
Yehia I. Mohamed ◽  
Aliya Qayyum ◽  
Manal Hassan ◽  
Lianchun Xiao ◽  
...  

e16659 Background: Child-Turcotte-Pugh (CTP) score is widely used in the assessment of prognosis of HCC and CTP-A is the standard criterion for active therapy and clinical trials entry. Recently, ALBI and insulin-like growth factor-1 (IGF)-CTP scores have been reported to improve survival prediction over CTP score. However, comparative studies to compare both scores and to integrate IGF into Albi score are lacking. Methods: After institutional board approval, data and samples were prospectively collected. 299 HCC patients who had data to generate both IGF-CPG and Albi index were used. The ALBI index, and IGF score were calculated, Cox proportional hazards models were fitted to evaluation the association between overall survival (OS) and CTP, IGF-CTP, Albi and IGF, albumin, bilirubin. Harrell’s Concordance index (C-index) was calculated to evaluate the ability of the three score system to predict overall survival. And the U-statistics was used to compare the performance of prediction of OS between the score system. Results: OS association with CTP, IGF-CTP and Albi was performed (Table). IGF-CTP B was associated with a higher risk of death than A (HR = 1.6087, 95% CI: 1.2039, 2.1497, p = 0.0013), ALBI grade 2 was also associated with a higher risk of death than 1 (HR = 2.2817, 95% CI: 1.7255, 3.0172, p < 0.0001). IGF-1(analyzed as categorical variable) was independently associated with OS after adjusting for the effects of ALBI grade. Which showed IGF-1 ≤26 was significantly associated with poor OS, P = 0.001. Conclusions: Although ALBI grade and IGF-CTP score in this analysis had similar prognostic values in most cases, their benefits might be heterogenous in some specific conditions. We looked into corporation of IGF-1 into ALBI grade, IGF score with cutoff ≤26 which clearly refined OS prediction and better OS stratification of ALBI-grade.


2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Shuyan Zhang ◽  
Shanshan Li ◽  
Jian-Lin Guo ◽  
Ningyi Li ◽  
Cai-Ning Zhang ◽  
...  

Background. Gastric cancer (GC) is a malignant tumour that originates in the gastric mucosal epithelium and is associated with high mortality rates worldwide. Long noncoding RNAs (lncRNAs) have been identified to play an important role in the development of various tumours, including GC. Yet, lncRNA biomarkers in a competing endogenous RNA network (ceRNA network) that are used to predict survival prognosis remain lacking. The aim of this study was to construct a ceRNA network and identify the lncRNA signature as prognostic factors for survival prediction. Methods. The lncRNAs with overall survival significance were used to construct the ceRNA network. Function enrichment, protein-protein interaction, and cluster analysis were performed for dysregulated mRNAs. Multivariate Cox proportional hazards regression was performed to screen the potential prognostic lncRNAs. RT-qPCR was used to measure the relative expression levels of lncRNAs in cell lines. CCK8 assay was used to assess the proliferation of GC cells transfected with sh-lncRNAs. Results. Differentially expressed genes were identified including 585 lncRNAs, 144 miRNAs, and 2794 mRNAs. The ceRNA network was constructed using 35 DElncRNAs associated with overall survival of GC patients. Functional analysis revealed that these dysregulated mRNAs were enriched in cancer-related pathways, including TGF-beta, Rap 1, calcium, and the cGMP-PKG signalling pathway. A multivariate Cox regression analysis and cumulative risk score suggested that two of those lncRNAs (LINC01644 and LINC01697) had significant prognostic value. Furthermore, the results indicate that LINC01644 and LINC01697 were upregulated in GC cells. Knockdown of LINC01644 or LINC01697 suppressed the proliferation of GC cells. Conclusions. The authors identified 2-lncRNA signature in ceRNA regulatory network as prognostic biomarkers for the prediction of GC patient survival and revealed that silencing LINC01644 or LINC01697 inhibited the proliferation of GC cells.


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.


2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 253-253
Author(s):  
Christine Cho-Shing Hsu ◽  
Abhishek Goyal ◽  
Rosa Hidalgo ◽  
Elizabeth Verna ◽  
Jean Emond ◽  
...  

253 Background: High alpha-fetoprotein (AFP) is associated with worse survival in hepatocellular carcinoma (HCC) patients. CA19-9 is a glycoprotein biomarker of biliary and pancreatic cancer. To our knowledge, no prospective study has examined CA19-9 as a prognostic biomarker in HCC. We hypothesized that it may add to our ability to risk stratify patients. Methods: We prospectively enrolled 122 patients with newly diagnosed HCC between 10/2008 and 7/2012 and followed until July 23, 2012. HCC was defined by AASLD criteria. CA 19-9 and AFP were measured on enrollment: 50% patients had CA19-9 >37 U/mL and 22% had CA 19-9>100. Pathology specimens were available for 50% of patients and none were consistent with mixed HCC-cholangiocarcinoma (HCC-CC) or pure CC. We evaluated the relationship between CA19-9 and overall survival using Kaplan Meier curves, univariate, and multivariate Cox Proportional Hazards Models. Results: The mean age of the cohort was 62.1 and 79% were male. 59% had underlying HCV and 16% had HBV. In univariate analysis, CA19-9>100 predicted worse survival (HR=3.44, 95% CI: 1.79-6.61, p=0.0002). Other cut-points for CA19-9 yielded similar results, although not all were significant. In a multivariate model including CP Score (B vs. A), Milan (outside vs. within), and AFP (>100 vs. ≤100), CA19-9 >100 remained an independent risk factor for increased mortality (HR 3.95, 95% CI: 1.95-7.97, p=0.0001). CP score and Milan status had HRs of 2.57 (95% CI: 1.31-5.02, p=0.006) and 5.27 (95% CI: 2.05-13.57 p=0.0006). AFP was not an independent risk factor for worse survival with a HR of 1.69 (95% CI: 0.85-3.37, p=0.14). We also looked at models using different cut-points for AFP; CA19-9 added additional risk stratification in all models. Among patients with AFP>100, median survival was 15.5 months vs. 3.8 months when comparing those with CA19-9 ≤100 with CA19-9>100 (p=0.01, log-rank). Conclusions: CA 19-9 is a readily available biomarker that may be a novel predictor of survival in HCC patients. In our multivariate model, CA 19-9>100 almost quadrupled mortality risk. It might be particularly useful to risk stratify patients with normal AFP and those with very high AFP being considered for transplant.


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 443-443
Author(s):  
Kerry Schaffer ◽  
Marcus Smith Noel ◽  
Aram F. Hezel ◽  
Alan W. Katz ◽  
Ashwani Sharma ◽  
...  

443 Background: Local-regional radioembolization with Yitrium-90 (Y-90) has become standard practice for patients with hepatocellular carcinoma (HCC) either as a bridge to transplant, or for local disease control. Outcomes data in the United States are limited and here we review our institutional experience with Y-90 radioembolization. Methods: We retrospectively reviewed charts from 70 patients with HCC who were treated with Y-90 from May 2010- January 2014. Clinical variables including Child-Pugh class and CLIP score were extracted from patient records. The Cox proportional hazards model was used to determine prognostic factors, and Kaplan-Meier curves were used to determine PFS and OS. Results: Median age was 61 (range 43-82), 79% Caucasian, 84% male, and 79% Child-Pugh class A. Median progression free survival (PFS) was 8.4 months (95% CI 6-10.7) and overall survival (OS) was 14.2 months (95% CI 9.7-21). Overall survival significantly differed by Child -Pugh score (p= 0.009), CLIP score (p=0.003), and presence of portal vein thrombosis (PVT) (p=0.0384), based on the log-rank test comparing Kaplan-Meier curves. Using univariate Cox proportional hazards models, both elevated baseline AFP, measured on a log scale (HR 1.79, 95% CI 1.32-2.43, p=0.0002) and post Y-90 treatment with sorafenib (HR=2.30, 95% CI 1.07-4.95, p=0.03) were associated with worse mortality. Elevated AFP (HR 2.45, 95% CI 1.73-3.47, p<0.0001) and Child-Pugh score of B (HR 4.83, 95% CI 2.23-10.43, p<0.0001) were associated with worse mortality in a multivariate Cox model adjusting for age and ethnicity. Furthermore, AFP values were significantly higher in the 10 patients who died within 4 months of Y-90 (p=0.001), and significantly lower in 7 patients who eventually received a liver transplant (p=0.0002). Conclusions: In patients undergoing treatment with Y-90 radioembolization, Child-Pugh class, CLIP score, presence of PVT, baseline AFP, and sorafenib post Y-90 were significantly associated with overall survival. Median PFS and OS data in this institutional cohort are encouraging. Further prospective studies on Y-90 treatment for HCC are warranted.


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.


2020 ◽  
Vol 7 (10) ◽  
Author(s):  
Kimberly C Claeys ◽  
Emily L Heil ◽  
Stephanie Hitchcock ◽  
J Kristie Johnson ◽  
Surbhi Leekha

Abstract Background Verigene Blood-Culture Gram-Negative is a rapid diagnostic test (RDT) that detects gram-negatives (GNs) and resistance within hours from gram stain. The majority of the data support the use of RDTs with antimicrobial stewardship (AMS) intervention in gram-positive bloodstream infection (BSI). Less is known about GN BSI. Methods This was a retrospective quasi-experimental (nonrandomized) study of adult patients with RDT-target GN BSI comparing patients pre-RDT/AMS vs post-RDT/pre-AMS vs post-RDT/AMS. Optimal therapy was defined as appropriate coverage with the narrowest spectrum, accounting for source and co-infecting organisms. Time to optimal therapy was analyzed using Kaplan-Meier and multivariable Cox proportional hazards regression. Results Eight-hundred thirty-two patients were included; 237 pre-RDT/AMS vs 308 post-RDT/pre-AMS vs 237 post-RDT/AMS, respectively. The proportion of patients on optimal antibiotic therapy increased with each intervention (66.5% vs 78.9% vs 83.2%; P &lt; .0001). Time to optimal therapy (interquartile range) decreased with introduction of RDT: 47 (7.9–67.7) hours vs 24.9 (12.4–55.2) hours vs 26.5 (10.3–66.5) hours (P = .09). Using multivariable modeling, infectious diseases (ID) consult was an effect modifier. Within the ID consult stratum, controlling for source and ICU stay, compared with the pre-RDT/AMS group, both post-RDT/pre-AMS (adjusted hazard ratio [aHR], 1.34; 95% CI, 1.04–1.72) and post-RDT/AMS (aHR, 1.28; 95% CI, 1.01–1.64), improved time to optimal therapy. This effect was not seen in the stratum without ID consult. Conclusions With the introduction of RDT and AMS, both proportion and time to optimal antibiotic therapy improved, especially among those with an existing ID consult. This study highlights the beneficial role of RDTs in GN BSI.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Rosero ◽  
P Jones ◽  
I Goldenberg ◽  
W Zareba ◽  
K Stein ◽  
...  

Abstract Background The role of cardiovascular implantable electronic device (CIED)-derived activity to predict inappropriate implantable cardioverter-defibrillator (ICD) therapy is not known. The Multicenter Automatic Defibrillator Implantation Trial – Reduce Inappropriate Therapy (MADIT-RIT) enrolled 1500 patients with contemporary indication for an ICD or a CRT-D. We aimed to identify whether activity, as a digital biomarker, predicted inappropriate therapy. Methods In 1500 patients enrolled in MADIT-RIT, CIED-derived patient activity was acquired daily. CIED-derived activity was averaged for the first 30 days following randomization and utilized in this study to predict inappropriate therapy post- 30-day. Kaplan-Meier survival analysis and multivariate Cox proportional hazards regression models were used to evaluate first inappropriate therapy by 30-day CIED-derived patient activity quintiles, and by 30-day device derived patient activity as a continuous measurement. Results There were a total of 1463 patients with activity data available (90%), 135 patients received at least one inappropriate therapy during the post-30 day follow-up period. Patients in the highest quintile (Q5) of CIED-derived activity (more active) were younger, more often males and more likely to have had a prior ablation of an atrial arrhythmia. Patients in the highest quintile of 30-day CIED-derived median activity had the highest risk of receiving inappropriate therapy, 21% at 2 years as compared 7–11% in the other four quintiles (Figure, p<0.001 for the overall duration). Patients with the highest level of 30-day median patient activity (Q5) had 1.75 times higher risk of any inappropriate therapy as compared with lower levels of activity, Q1-Q4 (HR=1.75, 95% CI: 1.23–2.50, p<0.002). Each 10% increase in CIED-derived 30-day median patient activity was associated with a significant, 73% increase in risk of receiving inappropriate therapy (HR=1.73, 95% CI: 1.17–2.54, p=0.005). Patients in the highest quintile for activity had a 68% increase in the risk of SVT excluding atrial fibrillation, atrial flutter or atrial tachycardia (HR=1.69, 95% CI: 1.26–2.25, p=0.004), despite 96% receiving beta-blocker medications. Inappropriate ICD Therapies by Activity Conclusions CIED-derived 30-day median patient activity predicted subsequent inappropriate therapy in ICD and CRT-D patients enrolled in MADIT-RIT. Patients with high levels of 30-day CIED-derived median patient activity were at a significantly higher risk of receiving inappropriate therapy. Activity, as a digital biomarker, may have utility in predicting and managing the risk of inappropriate therapy in this population. Acknowledgement/Funding Boston Scientific


Author(s):  
Jiazhe Lin ◽  
Nuan Lin ◽  
Wei-jiang Zhao

IntroductionGliomas account for 75% of the primary malignant brain tumors. The prognosis and treatment planning vary in lower-grade gliomas (LGG) due to their heterogeneous clinical behaviors. The dysregulation of autophagy-related (ATG) lncRNAs plays a crucial role in LGG. We aimed to develop and validate an ATG lncRNA risk signature, and a survival nomogram with integration of novel prognostic for LGG patients.Material and methodsDifferentially expressed ATG lncRNAs were screened out based on TCGA and GTEx RNA-seq databases. ATG lncRNA prognostic signature was then established by Kaplan–Meier, univariate Cox proportional hazards regression, Least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox proportional hazards regression, with its predictive value validated by time-dependent receiver operating characteristic (ROC) curves. Kaplan–Meier, univariate Cox regression and multivariate Cox proportional hazards regression were used to screen out clinical and molecular variables. A nomogram was developed and internally validated by ROC and calibration plots.ResultsAn ATG lncRNA risk signature was constructed with six differentially expressed lncRNAs (LINC00599, LINC02609, AC021739.2, AL118505.1, AL354892.2, and AL590666.2). Based on the risk signature, a nomogram was developed by addition of the significant prognostic clinical variables (age and grade) and molecular variables (IDH status and MGMT status).ConclusionsWe identified an ATG lncRNA risk signature and develop a nomogram for individualized survival prediction in LGG patients. A user-friendly free online calculator to facilitate the use of this nomogram among clinicians is also provided: https://linstu2009.shinyapps.io/LGGPRODICTORapp/?_ga=2.3154800.1506830296.1588641469-159983587.1588641469.


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