Dataset Information

Prediction of Survival Among Patients Receiving Transarterial Chemoembolization for Hepatocellular Carcinoma: A Response-Based Approach.

ABSTRACT: BACKGROUND AND AIMS:The heterogeneity of intermediate-stage hepatocellular carcinoma (HCC) and the widespread use of transarterial chemoembolization (TACE) outside recommended guidelines have encouraged the development of scoring systems that predict patient survival. The aim of this study was to build and validate statistical models that offer individualized patient survival prediction using response to TACE as a variable. APPROACH AND RESULTS:Clinically relevant baseline parameters were collected for 4,621 patients with HCC treated with TACE at 19 centers in 11 countries. In some of the centers, radiological responses (as assessed by modified Response Evaluation Criteria in Solid Tumors [mRECIST]) were also accrued. The data set was divided into a training set, an internal validation set, and two external validation sets. A pre-TACE model ("Pre-TACE-Predict") and a post-TACE model ("Post-TACE-Predict") that included response were built. The performance of the models in predicting overall survival (OS) was compared with existing ones. The median OS was 19.9 months. The factors influencing survival were tumor number and size, alpha-fetoprotein, albumin, bilirubin, vascular invasion, cause, and response as assessed by mRECIST. The proposed models showed superior predictive accuracy compared with existing models (the hepatoma arterial embolization prognostic score and its various modifications) and allowed for patient stratification into four distinct risk categories whose median OS ranged from 7 months to more than 4 years. CONCLUSIONS:A TACE-specific and extensively validated model based on routinely available clinical features and response after first TACE permitted patient-level prognostication.

SUBMITTER: Han G

PROVIDER: S-EPMC7496334 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Prediction of Survival Among Patients Receiving Transarterial Chemoembolization for Hepatocellular Carcinoma: A Response-Based Approach.

Han Guohong G Berhane Sarah S Toyoda Hidenori H Bettinger Dominik D Elshaarawy Omar O Chan Anthony W H AWH Kirstein Martha M Mosconi Cristina C Hucke Florian F Palmer Daniel D Pinato David J DJ Sharma Rohini R Ottaviani Diego D Jang Jeong W JW Labeur Tim A TA van Delden Otto M OM Pirisi Mario M Stern Nick N Sangro Bruno B Meyer Tim T Fateen Waleed W García-Fiñana Marta M Gomaa Asmaa A Waked Imam I Rewisha Eman E Aithal Guru P GP Travis Simon S Kudo Masatoshi M Cucchetti Alessandro A Peck-Radosavljevic Markus M Takkenberg R B RB Chan Stephen L SL Vogel Arndt A Johnson Philip J PJ

Hepatology (Baltimore, Md.) 20200527 1

<h4>Background and aims</h4>The heterogeneity of intermediate-stage hepatocellular carcinoma (HCC) and the widespread use of transarterial chemoembolization (TACE) outside recommended guidelines have encouraged the development of scoring systems that predict patient survival. The aim of this study was to build and validate statistical models that offer individualized patient survival prediction using response to TACE as a variable.<h4>Approach and results</h4>Clinically relevant baseline paramet ...[more]

PMID: 31698504

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Project description:PurposeThe purpose of this study was to investigate the predictive capability of neutrophil-to-apolipoprotein A1 ratio (NAR) for predicting overall survival (OS) among patients with hepatocellular carcinoma (HCC) receiving transarterial chemoembolization (TACE).Patients and methodsWe investigated the clinical features of 554 patients with HCC receiving TACE and assessed NAR's predictive value for OS with 222 patients (the discovery cohort) and 332 patients (the validation cohort). The association of NAR with circulation lectin-type oxidized low-density lipoprotein receptor-1-positive (LOX-1+ ) polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) was illustrated.ResultsMultivariate Cox regression revealed that lymphocyte count; Tumor, Node, Metastasis (TNM) stage; and NAR were independent prognostic factors in the discovery cohort. The validation cohort confirmed the independent prognostic value of TNM stage and NAR. Patients with low NAR (<2.7) displayed significantly increased OS in the discovery cohort (59.8 months vs. 21 months), the validation group (38.0 months vs. 23.6 months), and the total cohort (44.1 months vs. 22.0 months). A Cox proportional hazards model was used to combine Cancer of the Liver Italian Program (CLIP) score with discretized NAR. C-index illustrated that NAR-integrated CLIP score was the best model compared with NAR and CLIP score. Furthermore, NAR-CLIP presented superior predictive capacity for 10-, 20-, 30-, 40-, 50-, and 60-month survival compared with CLIP score by survival receiver-operator characteristic analysis in the discovery cohort, validation cohort, and total cohort. NAR was significantly associated with LOX-1+ PMN-MDSCs by linear regression.ConclusionThis study identified NAR as an independent predictor for OS among patients with HCC receiving TACE. NAR reflected circulation LOX-1+ PMN-MDSC level.Implications for practiceThe present study identified neutrophil-to-apolipoprotein A1 ratio (NAR) as an independent predictor for overall survival among patients with hepatocellular carcinoma receiving transarterial chemoembolization. NAR reflected circulation level of lectin-type oxidized low-density lipoprotein receptor-1-positive polymorphonuclear myeloid-derived suppressor cells.

Project description:PurposeTo investigate the role of contrast-enhanced magnetic resonance imaging (CE-MRI) radiomics for pretherapeutic prediction of the response to transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC).MethodsOne hundred and twenty-two HCC patients (objective response, n = 63; non-response, n = 59) who received CE-MRI examination before initial TACE were retrospectively recruited and randomly divided into a training cohort (n = 85) and a validation cohort (n = 37). All HCCs were manually segmented on arterial, venous and delayed phases of CE-MRI, and total 2367 radiomics features were extracted. Radiomics models were constructed based on each phase and their combination using logistic regression algorithm. A clinical-radiological model was built based on independent risk factors identified by univariate and multivariate logistic regression analyses. A combined model incorporating the radiomics score and selected clinical-radiological predictors was constructed, and the combined model was presented as a nomogram. Prediction models were evaluated by receiver operating characteristic curves, calibration curves, and decision curve analysis.ResultsAmong all radiomics models, the three-phase radiomics model exhibited better performance in the training cohort with an area under the curve (AUC) of 0.838 (95% confidence interval (CI), 0.753 - 0.922), which was verified in the validation cohort (AUC, 0.833; 95% CI, 0.691 - 0.975). The combined model that integrated the three-phase radiomics score and clinical-radiological risk factors (total bilirubin, tumor shape, and tumor encapsulation) showed excellent calibration and predictive capability in the training and validation cohorts with AUCs of 0.878 (95% CI, 0.806 - 0.950) and 0.833 (95% CI, 0.687 - 0.979), respectively, and showed better predictive ability (P = 0.003) compared with the clinical-radiological model (AUC, 0.744; 95% CI, 0.642 - 0.846) in the training cohort. A nomogram based on the combined model achieved good clinical utility in predicting the treatment efficacy of TACE.ConclusionCE-MRI radiomics analysis may serve as a promising and noninvasive tool to predict therapeutic response to TACE in HCC, which will facilitate the individualized follow-up and further therapeutic strategies guidance in HCC patients.

Project description:BackgroundDrug-eluting embolic transarterial chemoembolization (DEE-TACE) is an advance in TACE technique. However, at present there is insufficient evidence to support that DEE-TACE is superior to conventional TACE (cTACE) for hepatocellular carcinoma (HCC). The aim of this meta-analysis is to evaluate the efficacy and safety of TACE with CalliSpheres® microspheres (CSM-TACE) compared with cTACE in patients with HCC.Data sourcesPubMed, Embase, Web of Science, CNKI and Wanfang Databases were searched to identify relevant articles published before March 26, 2020. The data regarding treatment response, survival profile, adverse events and liver function indexes were retrieved.ResultsA total of 16 studies with 1454 HCC patients (722 treated with CSM-TACE and 732 with cTACE) were included. Patients receiving CSM-TACE had higher 1-month complete response (CR), objective response rate (ORR), disease control rate (DCR) (odds ratio (OR): 2.00, 95% confidence interval (95% CI): 1.29-3.09; OR: 2.87, 95% CI: 2.15-3.83; OR: 2.01, 95% CI: 1.37-2.95, respectively), 3-month CR, ORR, DCR (OR: 4.04, 95%CI: 2.46-6.64; OR: 3.39, 95%CI: 2.45-4.70; OR: 1.71, 95%CI: 1.14-2.55 respectively), and 6-month CR, ORR, DCR (OR: 4.02, 95%CI: 2.26-7.16; OR: 3.00, 95%CI: 2.05-4.38; OR: 2.66, 95%CI: 1.70-4.16 respectively) than those treated with cTACE. Furthermore, CSM-TACE exhibited a trend toward improved progression free survival (hazard ratio (HR): 0.86, 95%CI: 0.67-1.11) and overall survival (HR: 0.79, 95%CI: 0.59-1.07) over cTACE although these differences did not reach statistical significance. In terms of safety, the two TACE treatments showed similar post-treatment pain (OR: 0.84, 95%CI: 0.55-1.28), fever (OR: 0.99, 95%CI: 0.60-1.63), nausea/vomiting (OR: 0.84, 95% CI: 0.60-1.17), as well as 1-month follow-up alanine aminotransferase (Mean difference (MD): -3.66, 95%CI: -10.38-3.07), aspartate aminotransferase (MD: -2.30, 95%CI: -8.91-4.31) and total bilirubin (MD: -0.15, 95%CI: -2.26-1.96).ConclusionCSM-TACE displays superior treatment response, non-inferior survival profile and safety over cTACE in HCC patients.

Project description:Transarterial chemoembolization (TACE) is a commonly used treatment modality in hepatocellular carcinoma (HCC). The ability to identify patients who will respond to TACE represents an important clinical need, and tumor gene expression patterns may be associated with TACE response. We investigated whether tumor transcriptome is associated with TACE response in patients with HCC. We analyzed transcriptome data of treatment-naïve tumor tissues from a Chinese cohort of 191 HCC patients, including 105 patients who underwent TACE following resection with curative intent. We then developed a gene signature, TACE Navigator, which was associated with improved survival in patients that received either adjuvant or post-relapse TACE. To validate our findings, we applied our signature in a blinded manner to three independent cohorts comprising an additional 130 patients with diverse ethnic backgrounds enrolled in three different hospitals who received either adjuvant TACE or palliative TACE. TACE Navigator stratified patients into Responders and Non-Responders which was associated with improved survival following TACE in our test cohort (Responders: 67 months vs Non-Responders: 39.5 months, p<0.0001). In addition, multivariable Cox model demonstrates that TACE Navigator was independently associated with survival (HR: 9.31, 95% CI: 3.46-25.0, p<0.001). In our validation cohorts, the association between TACE Navigator and survival remained robust in both Asian patients who received adjuvant TACE (Hong Kong: 60 months vs 25.6 months p=0.007; Shandong: 61.3 months vs 32.1 months, p=0.027) and European patients who received TACE as primary therapy (Mainz: 60 months vs 41.5 months, p=0.041). These results indicate that a TACE-specific molecular classifier is robust in predicting TACE response. This gene signature can be used to identify patients who will have the greatest survival benefit after TACE treatment and enable personalized treatment modalities for patients with HCC.

Project description:ImportanceDefining early reliable surrogate end points for survival in patients with hepatocellular carcinoma (HCC) after conventional transarterial chemoembolization (cTACE) is of great value.ObjectiveTo evaluate the association between sustained response duration (SRD) and overall survival (OS) after cTACE for intermediate HCC.Design, setting, and participantsThis multicenter cohort study enrolled 2403 consecutive patients in China with naive intermediate HCC between June 1, 2000, and December 31, 2008, as the primary cohort, and 331 consecutive patients with intermediate naive HCC between January 1, 2011, to June 30, 2012, as the validation cohort. All patients received cTACE as an initial treatment. Initial response and best response were defined as the radiological response after first cTACE or best radiological response after 2 or more sessions of cTACE, respectively. Responders were those who experienced complete response or partial response. Sustained response duration was defined as the time between the date when complete response, partial response, or stable disease was achieved and the date progressive disease occurred after cTACE. Response was evaluated by modified Response Evaluation Criteria in Solid Tumors. Information about patients in the study was collected from January 1, 2018, to March 31, 2018, and analysis of these data was performed in April 2018.Main outcomes and measuresOverall survival.ResultsA total of 2734 total patients (2499 of 2734 [91.4%] male; median [range] age, 56.5 [18-75] years) were included in the analysis. In the primary cohort, SRD of 6 months or more was found to have the strongest association with 5-year OS after cTACE among different durations of sustained response. Patients with SRD of 6 months or more (387 of 430 male; median [range] age, 57 [18-75] years) had the longest median (range) OS (67.7 [64.8-72.1] months), followed by initial responders (760 of 874 male; median [range] age, 56 [18-75] years; median [range] OS, 55.8 [55.0-57.7] months) and best responders (939 of 1032 male; median [range] age, 57 [18-75] years; median [range] OS, 53.2 [52.2-54.6] months). Response duration of 6 months or more was found to be an independent prognostic factor for OS (hazard ratio, 0.145; 95% CI, 0.124-0.170; P < .001). The significance of SRD as a factor associated with OS was confirmed in the validation cohort.Conclusions and relevanceSustained response duration of 6 months or more was associated with OS and may serve as an early surrogate end point after cTACE for intermediate HCC.

Project description:Transarterial chemoembolization (TACE) is the mainstay of treatment for patients with intermediate/advanced stage or unresectable hepatocellular carcinoma (HCC). Despite the palliative nature of TACE treatment, embolizing the tumor feeding vessels and leading to progressive tumor necrosis, complete response (CR) after TACE could still be observed in a certain population. Thus, this study aimed to investigate both the predictors for CR and the long-term prognosis of the patients with CR after TACE. The study recruited new diagnosed HCC patients initially treated with TACE from 2010 to 2013. Post TACE response was assessed by scheduled image studies according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Then, pre-TACE factors were compared between patients with and without CR. After the first session of TACE, 22.3% of the 669 TACE treated patients achieved CR. During a median of 26.6 months follow-up, patients with CR had better overall survival than those without (median: 35.8 vs. 24.0 months, P<0.001). By multivariate logistic regression analysis, Child-Turcotte-Pugh class B (OR: 0.419, P=0.005), tumor burden beyond up-to-7 criteria (OR: 0.118, P<0.001), bilobar tumor extent (OR: 0.236, P<0.001), higher alpha-fetoprotein (AFP) level (≥20 ng/ml, OR: 0.614, P=0.039) and higher platelet counts (>150 k/μl, OR: 0.482, P=0.002) were unfavorable predictors for CR after first TACE. In addition, macrovascular invasion (HR: 3.113, P=0.001) and higher AFP levels (≥15 ng/ml, HR: 2.601, P=0.007) were predictors for early HCC recurrence whereas diabetes mellitus (DM) (HR: 2.166, P=0.006) was the only significant predictor for late HCC recurrence in CR patients. In conclusion, more than one-fifth of HCC patients achieved CR after first TACE and these patients had favorable prognosis. Furthermore, tailored post-TACE follow-up strategies shall be considered in patients with different risk factors of early or late recurrence after CR.

Dataset Information

Prediction of Survival Among Patients Receiving Transarterial Chemoembolization for Hepatocellular Carcinoma: A Response-Based Approach.

Publications

Prediction of Survival Among Patients Receiving Transarterial Chemoembolization for Hepatocellular Carcinoma: A Response-Based Approach.

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