Transarterial Chemoembolization Response Research Articles

Enhanced interactions within microenvironment accelerates dismal prognosis in HBV-related HCC after TACE.

Transarterial chemoembolization (TACE) is the first-line treatment for patients with advanced HCC, but there are limited studies on the microenvironment alterations caused by TACE. Six fresh HBV-related HCC specimens with or without TACE intervention were used to perform single-cell RNA sequencing. The 757 bulk samples from 3 large-scale multicenter cohorts were applied for comprehensive analysis. The biological functions of the biomarkers were further validated by phenotypic experiments. Using single-cell RNA sequencing analysis, we delineated the global cell atlas of post-TACE and demonstrated elevated tumor heterogeneity and an enhanced proinflammatory microenvironment induced by TACE. Cell-cell communication analysis revealed that markedly elevated interactions between NABP1+ malignant hepatocytes, neutrophils, and CD8+ T cells after TACE might accelerate the shift from CD8+ effector memory T cells to CD8+ effector T cells. This result was substantiated by the developmental trajectory between the 2 and dramatically decreased resident scores along the pseudotemporal trajectory. Integrating bulk data, we further found that the increased estimated proportion of NABP1+ malignant hepatocytes was related to poor TACE response and dismal prognosis, and its biomarker role could be replaced by NABP1. In vitro, multiple biological experiments consistently verified that NABP1 knockdown significantly inhibited the proliferation and migration of HCC cells. Based on our depicted global map of post-TACE, we confirmed that the enhanced interactions within the microenvironment after TACE may be the culprits for postoperative progression. NABP1 may become an attractive tool for the early identification of patients sensitive to first-line TACE in clinical practice.

Defining a radiomics feature selection method for predicting response to transarterial chemoembolization in hepatocellular carcinoma patients

AimTo assess the utility of different radiomics feature selection methods in predicting transarterial chemoembolization (TACE) response in hepatocellular carcinoma (HCC) patients. Materials and methodsThis study employed a dataset of 136 paired MR T1-weighted contrast-enhanced abdominal images with liver tumor masks before and after TACE. TACE response for each image pair was classified by European Association for the Study of the Liver (EASL) and modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines. 100D feature vectors were generated for the paired tumor areas. Eighteen existing feature selection methods were employed to select the top-k features to train and test a non-linear support vector machine (SVM) with a Gaussian kernel. Five-cross validation was performed to identify the highest performing feature selection methods. ResultsFor all benchmarks, a L0-based method selecting the top-5 or top-10 features achieved the highest performance. For images classified with EASL criteria that were analyzed with the L0-based method, the accuracy (ACC), area under curve (AUC), and balanced F score (F1-score) were 0.75 ​± ​0.06, 0.75 ​± ​0.09, and 0.80 ​± ​0.05, respectively. For images classified with mRECIST criteria that were analyzed with the L0-based method, the ACC, AUC, and F1-score were 0.75 ​± ​0.07, 0.71 ​± ​0.16, and 0.82 ​± ​0.04, respectively. ConclusionA L0-based method that selected the top-5/10 most important features predicted TACE response in HCC patients with the highest accuracy under both EASL and mRECIST criteria. This proof-of-concept investigation represents a step forward in the development of a reliable clinical decision-making tool for management of intermediate HCC patients undergoing TACE.

An Oxidative Stress-Related Prognostic Signature Predicts Treatment Response and Outcomes for Hepatocellular Carcinoma After Transarterial Chemoembolization.

Oxidative stress plays a critical role in promoting tumor resistance to hypoxia and chemotherapeutic drugs. However, the prognostic role of oxidative stress-related genes (OSRGs) in hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) has not been fully explored. We used transcriptome data from the GSE104580 cohort containing patients marked as responders or nonresponders to TACE therapy to identify differentially expressed OSRGs associated with TACE response (TR-OSRGs). We created a TR-OSRG prognostic signature based on TR-OSRGs using least absolute shrinkage and selection operator Cox and stepwise Cox regression analyses in a training cohort of patients with HCC (TCGA-LIHC). We verified this prognostic signature in two external cohorts of patients who received TACE for HCC (GSE14520-TACE and ZS-TACE-37). Finally, we constructed a prognostic nomogram model for predicting survival probability of patients with HCC based on Cox regression analysis. The TR-OSRG prognostic signature was created and shown to be a robust independent prognostic factor for treatment response and outcomes for HCC after TACE therapy. Risk scores based on this signature correlated with tumor stage and grade. Tumor samples from patients with higher risk scores exhibited more infiltration of immune cells and significantly increased expression of immune checkpoint genes. We also developed a nomogram for patients with HCC based on the TR-OSRG prognostic signature and clinical parameters; this nomogram was a useful quantitative analysis tool for predicting patient survival. The TR-OSRGs signature exhibited good performance in predicting treatment response and outcomes in patients with HCC treated with TACE.

The Role of GNMT and MMP12 Expression in Determining TACE Efficacy: Validation at Transcription and Protein Levels.

Transarterial chemoembolization (TACE) represents a significant therapeutic modality for hepatocellular carcinoma (HCC). We aimed to develop a gene signature to accurately predict patient TACE response and explore the underlying mechanisms. Three independent datasets were utilized, including GSE104580, GSE14520 and external validation from the Cancer Hospital Chinese Academy of Medical Sciences. GSE104580 was randomly partitioned into a training set and a validation set, whereas GSE14520 was categorized into a resection group and a TACE group. Logistic regression was used to develop a TACE effectiveness model. Immunohistochemistry is utilized to confirm the protein expression trends of the signature genes. Immune infiltration and functional enrichment analyses were conducted to investigate the potential underlying mechanisms. A 2-gene signature consisting of glycine N-methyltransferase (GNMT) and matrix metalloproteinase-12 (MMP12) was constructed, and based on this, all the patients were assigned TACE effectiveness scores and categorized into high effectiveness (HE) and low effectiveness (LE) groups. The HE group exhibited a better prognosis than the LE group in the various cohorts (p < 0.05). In the external validation set, immunohistochemistry confirmed the expression of the signature genes exhibiting an upregulated trend of GNMT in the HE group and MMP12 in the LE group, the LE group also exhibited a poorer prognosis [for overall survival (OS), HE group: 881 days vs LE group: 273 days (p < 0.05), and for progression-free survival (PFS), HE group: 458 days vs LE group: 136 days (p < 0.05)]. Multivariate analysis in all the datasets identified LE status as an independent risk factor for OS, disease-free survival (DFS) and PFS. The infiltration level of M0 macrophages and activated mast cells in the LE group was significantly higher than in the HE group. The hypoxia signaling pathway and glycolysis pathway were significantly enriched in the LE group. The loss of GNMT and the overexpression of MMP12 may be critical factors influencing TACE efficacy.

Multifocal hepatocellular carcinoma: a narrative review assessing treatment options from the interventional radiologist’s perspective.

It is estimated that 35-40% of hepatocellular carcinoma (HCC) patients present with multiple nodules at the time of diagnosis. Treating multifocal disease is difficult given patient population heterogeneity. Multiple interventional radiological (IR) options, including ablation, transarterial chemoembolization (TACE), and transarterial radioembolization (TARE), are available, each with its own merits and limitations. Our aim is to explore the current state of the literature to identify where each of these options is best applied to multifocal HCC management. A narrative literature review of 107 papers was performed in PubMed. Articles from 2010 and newer were used for clinical data and for classification/scoring system details. The majority of the keywords for searches include the treatment modality name alongside terms such as "HCC", "multifocal", or "multinodular". Ablation is a curative option for Barcelona Clinic Liver Cancer (BCLC) A disease and is appropriate when liver transplantation (LT) is impractical. It is ideal in disease with ?3 nodules (each <3 cm) preferably confined to one segment. TACE [conventional TACE (cTACE), drug-eluting bead TACE (DEB-TACE), balloon-occluded TACE (B-TACE), and less so hepatic arterial infusion chemotherapy (HAIC)] is the major workhorse for multifocal BCLC B disease, in pre-transplant downstaging, and in advanced disease palliation. The Kinki BCLC B subclassification can guide TACE subtype selection. TACE response can be assessed over 2-3 sessions per modified Response Evaluation Criteria in Solid Tumors (mRECIST) and patient session tolerance. TARE is an option for BCLC C disease, with BCLC A/B applications limited by radiation induced liver disease (RILD). Pseudo-ablative techniques like sub-selective TARE (sTARE) are promising but are unproven and less useful in multinodular disease. Finally, combination therapies [TACE + ablation, liver resection (LR) + ablation/TACE] are an exciting option but warrant further study. Multifocal HCC remains challenging to manage. While BCLC is a useful starting point, the patient's tumor imaging characteristics and clinical circumstances must be considered when selecting the appropriate treatment modality.

Impact of Trans-Arterial Chemo-Embolization on Tumor Response in Hepatocellular Carcinoma Patients: A Retrospective Study

Trans-arterial Chemo-embolization is a treatment done for hepatic metastatic tumors caused by Chronic Liver Disease to reduce the tumor load on the liver. Objective: To assess the treatment response of TACE (Trans-Arterial Chemo-Embolization) in patients with HCC (Hepatocellular Carcinoma) based on the m-RECIST criteria. Methods: The retrospective study was conducted for a duration of one year; from December 2021 to December 2022. The Data were collected from Allied Hospital Faisalabad. TACE was done on a total of 80 patients with Hepatocellular Carcinoma ages between 31 to 80 years and the response was evaluated by m-RECIST criteria on a CT Triphasic scan. The chi-square test was used to find the association between gender and tumor response. Results: A total of 80 TACE-treated patients of Hepatocellular Carcinoma, (n=56) 70% were males and (n=24) 30% were females. Tumor response was evaluated as CR in (n=45) 56% of patients, (n=26) 32% showed PR, (n=6) 8% had SD, while (n=3) 4% had PD. Most of the patients showed significant tumor necrosis, 70-90% tumor necrosis was seen in 52% of the patients. An association between gender (male participants; n=56) and tumor response to TACE (71 responded out of which 56 were males) was found to be significant. Conclusions: TACE is a better treatment option for unresectable and larger HCC if proper care, management, and continuation of disease assessment are done after the treatment, as it results in tumor burden reduction and improved chances of qualifying for liver transplant in suitable cases.

TACE responser NDRG1 acts as a guardian against ferroptosis to drive tumorgenesis and metastasis in HCC

BackgroundThe treatment efficacy of transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) varies widely between individuals. The aim of this study was to identify subtype landscapes and responser related to TACE, and further clarify the regulatory effect and corresponding mechanism of NDRG1 on HCC tumorgenesis and metastasis.MethodsThe principal component analysis (PCA) algorithm was used to construct a TACE response scoring (TRscore) system. The random forest algorithm was applied to identify the TACE response-related core gene NDRG1 of HCC, and its role in the prognosis of HCC was explored. The role of NDRG1 in the progression and metastasis of HCC and functional mechanism were confirmed using several experimental methods.ResultsBased on the GSE14520 and GSE104580 cohorts, we identified 2 TACE response-related molecular subtypes for HCC with significant differences in clinical features, and the TACE prognosis of Cluster A was significantly better than that of Cluster B (p < 0.0001). We then established the TRscore system and found that the low TRscore group showed a higher probability of survival and a lower rate of recurrence than the high TRscore group (p < 0.05) in both the HCC and TACE-treated HCC cohorts within the GSE14520 cohort. NDRG1 was determined to be the the hub gene associated with the TACE response of HCC and its high expression suggested a poor prognosis. Furthermore, The suppression of NDRG1 konckdown in tumorgenesis and metastasis of HCC was clarified in both vivo and vitro, which was importantly achieved through inducing ferroptosis in HCC cells, especially contributing to RLS3-induced ferroptosis.ConclusionThe constructed TACE response-related molecular subtypes and TRscores can specifically and accurately predict TACE prognosis for HCC. In addition, the TACE response-related hub gene NDRG1 may act as a guardian against ferroptosis to drive tumorgenesis and metastasis in HCC, which laid a new foundation for the development of new potential targeted therapy strategies to improve disease prognosis in HCC patients.

Assessment of Transarterial Chemoembolization Using Super-resolution Ultrasound Imaging and a Rat Model of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a highly prevalent form of liver cancer diagnosed annually in 600,000 people worldwide. A common treatment is transarterial chemoembolization (TACE), which interrupts the blood supply of oxygen and nutrients to the tumor mass. The need for repeat TACE treatments may be assessed in the weeks after therapy with contrast-enhanced ultrasound (CEUS) imaging. Although the spatial resolution of traditional CEUS has been restricted by the diffraction limit of ultrasound (US), this physical barrier has been overcome by a recent innovation known as super-resolution US (SRUS) imaging. In short, SRUS enhances the visible details of smaller microvascular structures on the 10 to 100 µm scale, which unlocks a host of new clinical opportunities for US. In this study, a rat model of orthotopic HCC is introduced and TACE treatment response (to a doxorubicin-lipiodol emulsion) is assessed using longitudinal SRUS and magnetic resonance imaging (MRI) performed at 0, 7 and 14 d. Animals were euthanized at 14 d for histological analysis of excised tumor tissue and determination of TACE response, that is, control, partial response or complete response. CEUS imaging was performed using a pre-clinical US system (Vevo 3100, FUJIFILM VisualSonics Inc.) equipped with an MX201 linear array transducer. After administration of a microbubble contrast agent (Definity, Lantheus Medical Imaging), a series of CEUS images were collected at each tissue cross-section as the transducer was mechanically stepped at 100 μm increments. SRUS images were formed at each spatial position, and a microvascular density metric was calculated. Microscale computed tomography (microCT, OI/CT, MILabs) was used to confirm TACE procedure success, and tumor size was monitored using a small animal MRI system (BioSpec 3T, Bruker Corp.). Although there were no differences at baseline (p > 0.15), both microvascular density levels and tumor size measures from the complete responder cases at 14 d were considerably lower and smaller, respectively, than those in the partial responder or control group animals. Histological analysis revealed tumor-to-necrosis levels of 8.4%, 51.1% and 100%, for the control, partial responder and complete responder groups, respectively (p < 0.005). SRUS imaging is a promising modality for assessing early changes in microvascular networks in response to tissue perfusion-altering interventions such as TACE treatment of HCC.

Association of myosteatosis with treatment response and survival in patients with hepatocellular carcinoma undergoing chemoembolization: a retrospective cohort study

Patients with hepatocellular carcinoma (HCC) have poor prognosis and have frequent treatment-related toxicities resulting in cancer-associated cachexia. This study aimed to determine the association of myosteatosis and sarcopenia on mortality in patients with HCC treated with transarterial chemoembolization (TACE). Six hundred and eleven patients diagnosed with HCC and underwent TACE at a tertiary care center between 2008 and 2019 were included. Body composition was assessed using axial CT slices at level L3 to calculate the skeletal muscle density for myosteatosis and skeletal muscle index for sarcopenia. The primary outcome was overall survival while the secondary outcome was TACE response. Patients with myosteatosis had a poorer TACE response than patients without myosteatosis (56.12% vs. 68.72%, adjusted odds ratio [OR] 0.49, 95% confidence interval [CI] 0.34–0.72). The rate of TACE response in patients with sarcopenia was not different from those without sarcopenia (60.91% vs. 65.22%, adjusted OR 0.79, 95% CI 0.55–1.13). Patients with myosteatosis had shorter overall survival than without myosteatosis (15.9 vs. 27.1 months, P < 0.001). In the multivariable Cox regression analysis, patients with myosteatosis or sarcopenia had higher risk of all-cause mortality than their counterparts (adjusted hazard ratio [HR] for myosteatosis versus no myosteatosis 1.66, 95% CI 1.37–2.01, adjusted HR for sarcopenia versus no sarcopenia 1.26, 95% CI 1.04–1.52). Patients with both myosteatosis and sarcopenia had the highest 7 year mortality rate at 94.45%, while patients with neither condition had the lowest mortality rate at 83.31%. The presence of myosteatosis was significantly associated with poor TACE response and reduced survival. Identifying patients with myosteatosis prior to TACE could allow for early interventions to preserve muscle quality and might improve prognosis in HCC patients.

Multi-algorithms analysis for pre-treatment prediction of response to transarterial chemoembolization in hepatocellular carcinoma on multiphase MRI

ObjectivesThis study compared the accuracy of predicting transarterial chemoembolization (TACE) outcomes for hepatocellular carcinoma (HCC) patients in the four different classifiers, and comprehensive models were constructed to improve predictive performance.MethodsThe subjects recruited for this study were HCC patients who had received TACE treatment from April 2016 to June 2021. All participants underwent enhanced MRI scans before and after intervention, and pertinent clinical information was collected. Registry data for the 144 patients were randomly assigned to training and test datasets. The robustness of the trained models was verified by another independent external validation set of 28 HCC patients. The following classifiers were employed in the radiomics experiment: machine learning classifiers k-nearest neighbor (KNN), support vector machine (SVM), the least absolute shrinkage and selection operator (Lasso), and deep learning classifier deep neural network (DNN).ResultsDNN and Lasso models were comparable in the training set, while DNN performed better in the test set and the external validation set. The CD model (Clinical & DNN merged model) achieved an AUC of 0.974 (95% CI: 0.951–0.998) in the training set, superior to other models whose AUCs varied from 0.637 to 0.943 (p < 0.05). The CD model generalized well on the test set (AUC = 0.831) and external validation set (AUC = 0.735).ConclusionsDNN model performs better than other classifiers in predicting TACE response. Integrating with clinically significant factors, the CD model may be valuable in pre-treatment counseling of HCC patients who may benefit the most from TACE intervention.

Recommendation of mHAP and ABCR scoring systems for the decision-making of the first and subsequent TACE session in HCC patients.

Due to the high heterogeneity among hepatocellular carcinoma (HCC) patients receiving transarterial chemoembolization (TACE), the prognosis of patients varies significantly. Various predictive scoring systems have been developed to identify the patients who could benefit from TACE. However, there is no consensus on which is better. This study aims to validate and compare the predictive capabilities of scoring systems for first and subsequent TACE. A total of 524 HCC patients were treated with TACE, and 222 patients who met the inclusion criteria were included. Log-rank test was used to verify the predictive value of six scoring systems for the first TACE and four TACE retreatment scoring systems. Harrell's concordance (C)-index, likelihood ratio and integrated Brier score (IBS) were used to compare the predictive performance. For the scoring systems of TACE, the overall survival (OS) of candidates screened by Hepatoma Arterial-embolization Prognostic (HAP), modified HAP (mHAP), mHAP3, alpha-fetoprotein, Barcelona Clinic Liver Cancer, Child-Pugh and Response (ABCR), albumin-bilirubin grade (ALBI), tumor size, alpha-fetoprotein, first TACE response and pre-/post-TACE was significantly longer than that of the noncandidates (all P < 0.05), whereas the mHAP2 and assessment for retreatment with TACE did not distinguish the candidates from noncandidates (P = 0.206, 0.115, respectively). The predictive and calibration performances of mHAP and ABCR were the highest for the first TACE and TACE retreatment, respectively. mHAP identifies the patients who could benefit from the first TACE, whereas ABCR distinguishes patients who could benefit from subsequent TACE sessions.

CT-radiomics and clinical risk scores for response and overall survival prognostication in TACE HCC patients

We aimed to identify hepatocellular carcinoma (HCC) patients who will respond to repetitive transarterial chemoembolization (TACE) to improve the treatment algorithm. Retrospectively, 61 patients (mean age, 65.3 years ± 10.0 [SD]; 49 men) with 94 HCC mRECIST target-lesions who had three consecutive TACE between 01/2012 and 01/2020 were included. Robust and non-redundant radiomics features were extracted from the 24 h post-embolization CT. Five different clinical TACE-scores were assessed. Seven different feature selection methods and machine learning models were used. Radiomics, clinical and combined models were built to predict response to TACE on a lesion-wise and patient-wise level as well as its impact on overall-survival prognostication. 29 target-lesions of 19 patients were evaluated in the test set. Response rates were 37.9% (11/29) on the lesion-level and 42.1% (8/19) on the patient-level. Radiomics top lesion-wise response prognostications was AUC 0.55–0.67. Clinical scores revealed top AUCs of 0.65–0.69. The best working model combined the radiomic feature LargeDependenceHighGrayLevelEmphasis and the clinical score mHAP_II_score_group with AUC = 0.70, accuracy = 0.72. We transferred this model on a patient-level to achieve AUC = 0.62, CI = 0.41–0.83. The two radiomics-clinical features revealed overall-survival prognostication of C-index = 0.67. In conclusion, a random forest model using the radiomic feature LargeDependenceHighGrayLevelEmphasis and the clinical mHAP-II-score-group seems promising for TACE response prognostication.

Circulating MiRNA-373 as a Predictor of Response to Super-selective Transarterial Chemoembolization Bridging Therapy in Hepatocellular Carcinoma Patients Awaiting Liver Transplantation.

Super selective transarterial chemoembolization (TACE) has emerged as a bridging therapy for early hepatocellular carcinoma (HCC) patients awaiting liver transplantation. This study aimed at assessing the expression profiles of circulating MiR-210 and MiR-373 as potential predictors of response to TACE bridging therapy in a group of Egyptian HCC cases on top of chronic hepatitis-C infection, awaiting liver transplantation. Fifty-three HCC cases awaiting liver transplantation referred for TACE, were followed up for three months, resulting in forty-five responders and eight non-responders based on modified response evaluation criteria in solid tumors (mRECIST). Circulating pre TACE MiR-210 and MiR-373 expressions were determined using reverse transcription quantitative polymerase chain reaction. Circulating pre TACE MiR-373, but not MiR-210, was significantly higher in non-responders than responders. Receiver operating characteristics (ROC) curve analysis of MiR-373, pre-TACE tumor volume, inflammatory score, and albumin bilirubin (ALBI) grade revealed highest sensitivity for pre-TACE tumor volume (cutoff>11.49 cm3) and highest specificity for pre-TACE MiR-373 (cutoff>1.46-fold change). Multivariate logistic regression revealed pre TACE MiR-373 as a significant independent predictor of TACE response after adjusting for pre TACE tumor volume. Circulating pre-TACE MiR-373 could assist as a noninvasive predictor marker of response to TACE bridging therapy in early HCC patients awaiting liver transplantation.

A Three-Gene Signature for Predicting the Prognosis of Patients Treated with Transarterial Chemoembolization (TACE) and Identification of PD-184352 as a Potential Drug to Reverse Nonresponse to TACE.

Background Transarterial chemoembolization (TACE) is a first-line treatment for patients with unresectable hepatocellular carcinoma (HCC). Owing to differences in its efficacy across individuals, determining the indicators of patient response to TACE and finding approaches to reversing nonresponse thereto are necessary. Methods Transcriptome data were obtained from the GSE104580 dataset, in which patients were marked as having TACE response or nonresponse. We identified differentially expressed genes (DEGs) and performed Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. We screened genes with a prognostic value for TACE in the HIF-1 signaling pathway by univariate regression analysis. By using least absolute shrinkage and selection operator (LASSO) Cox regression, we established a multigene signature in GSE14520, which we verified using a drug sensitivity test. The Connectivity Map (CMap) database was used to find potential drugs to reverse nonresponse to TACE. Results We constructed a prognostic signature consisting of three genes (erythropoietin (EPO), heme oxygenase 1 (HMOX1), and serine protease inhibitor 1 (SERPINE1)) that we validated by drug sensitivity test. After dividing patients treated with TACE into high- and low-risk groups based on this new signature, we showed that overall survival (OS) of the high-risk group was significantly lower than that of the low-risk group and that the risk score was an independent predictor of OS in patients treated with TACE. Based on our CMap findings, we speculated that PD-184352, an inhibitor of mitogen-activated protein kinase (MEK), had potential as a drug treatment to reverse nonresponse to TACE. We confirmed this speculation by using PD-184352 in a cell promotion experiment in a TACE environment. Conclusion We constructed a TACE-specific three-gene signature that could be used to predict HCC patients' responses to and prognosis after TACE treatment. PD-184352 might have potential as a drug to improve TACE efficacy.

Mathematical modeling of cancer cells and vasculature dynamics with serological and imaging biomarkers suggests synergistic effects of TACE and TKIs in HCC patients

Background and Aims: Transarterial-chemoembolization (TACE) and tyrosine-kinase inhibitors (TKI) represent first-line treatments in intermediate and advanced hepatocellular carcinoma (HCC). Deepening TKI and TACE response mechanisms may provide insights to optimize their combination. We developed a physic-mathematical model to analyze cancer cells and tumor vasculature dynamics in HCC patients (pts) using serum biomarkers combined with tumor digital imaging before and after TACE or TKI treatment.

Prothrombin induced by vitamin K absence or antagonist-II (PIVKA-II) predicts complete responses of transarterial chemoembolization for hepatocellular carcinoma

Prothrombin Induced by Vitamin K Absence or Antagonist-II (PIVKA-II) is a diagnostic marker for hepatocellular carcinoma (HCC). Transarterial chemoembolization (TACE) is the standard management for intermediate stage HCC but lacks effective response predictors. We investigated the utility of PIVKA-II as a predictor of TACE response. This prospective study included consecutive patients with HCC undergoing TACE in Taiwan. Serum PIVKA-II levels were measured before and serially after TACE. Multivariable analyses were conducted to evaluate predictors of mortality, complete responses (CR) to TACE and unTACEable progression. We included 46 patients with HCC (median age: 64 years, men:72%), and Barcelona Clinic Liver Cancer (BCLC) stages A (17%), B (65%), or C (17%). Before TACE, the median PIVKA-II level was 189 mAU/mL. After a median follow-up of 16 months, 27 (59%) patients died. PIVKA-II was positively correlated with tumor burden. Patients with infiltrative HCC or HCC exceeding the up-to-7 criteria had significantly higher baseline PIVKA-II levels than those without. Multivariable analysis indicated the infiltrative HCC independently predicted mortality. In patients BCLC A and B (n=38), low baseline PIVKA-II (<26 mAU/mL) predicted CR to TACE, whereas high PIVKA-II predicted unTACEable tumor progression. Observations from a validation cohort corroborated the initial result that low PIVKA-II predicts CR. Moreover, serial PIVKA-II levels post TACE were significantly lower in patients with a CR to TACE compared with those without. Low baseline PIVKA-II level helps to predict a CR of TACE in patients with HCC.

Volumetric Analysis of Hepatocellular Carcinoma After Transarterial Chemoembolization and its Impact on Overall Survival.

To evaluate the prognostic value of Response Evaluation Criteria In Solid Tumors (RECIST), modified RECIST and volumetric analysis in patients with hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE). This single-center prospective cohort study included a total of 61 patients with HCC treated by transarterial chemoembolization (TACE). The response of TACE was evaluated on preprocedural and postprocedural CT by two radiologists using RECIST/mRECIST and volumetric response to treatment. Each response assessment method was used to classify the response as progressive disease, stable disease, partial response and complete response. Kaplan-Meier analysis with log-rank test was performed for each method to evaluate its ability to help predict overall survival and progression free survival. Interobserver variability and reproducibility was determined by the Pearson and Spearman correlation coefficients. The median overall survival was 17.1 months and the median progression-free survival was 11.1 months. Volumetric assessment was proved to be a prognostic factor for overall survival (p<0.01) and progression-free survival (p<0.001), contrasting with RECIST and mRECIST. All three methods featured very small interobserver variability (p<0.001 for Pearson and Spearman correlation coefficients). The patients classified as having stable disease had a 3.8-fold higher risk of death than the patients classified as having a complete/partial response (HR=3.82; 95% Confidence Interval (CI)=1.32-11.02; p=0.013) and a 4.5-fold higher risk of progression (HR=4.46; 95% CI=1.72-11.61; p=0.002). The prognostic value of volumetric analysis in patients with HCC treated by TACE appears to be superior to RECIST and mRECIST, with a real impact in everyday practice.

Artificial Intelligent Multi-Modal Point-of-Care System for Predicting Response of Transarterial Chemoembolization in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) ranks the second most lethal tumor globally and is the fourth leading cause of cancer-related death worldwide. Unfortunately, HCC is commonly at intermediate tumor stage or advanced tumor stage, in which only some palliative treatment can be used to offer a limited overall survival. Due to the high heterogeneity of the genetic, molecular, and histological levels, HCC makes the prediction of preoperative transarterial chemoembolization (TACE) efficacy and the development of personalized regimens challenging. In this study, a new multi-modal point-of-care system is employed to predict the response of TACE in HCC by a concept of integrating multi-modal large-scale data of clinical index and computed tomography (CT) images. This multi-modal point-of-care predicting system opens new possibilities for predicting the response of TACE treatment and can help clinicians select the optimal patients with HCC who can benefit from the interventional therapy.

Systemic Inflammation Response Index is a Prognostic Risk Factor in Patients with Hepatocellular Carcinoma Undergoing TACE.

BackgroundMounting evidence has shown that systemic inflammation response index (SIRI), a novel prognostic biomarker based on peripheral lymphocyte, neutrophil and monocyte counts, is associated with poor prognosis for several tumors. However, the prognostic value of SIRI in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) is elusive. Herein, we aimed to evaluate the correlation between SIRI and clinical outcomes in these patients.MethodsA total of 194 consecutive patients who underwent TACE were included in this study. Patients were stratified into high and low SIRI groups based on the cut-off value using receiver operating characteristic (ROC) analysis. Independent risk factors for tumor response were analyzed using forward stepwise logistic regression. A one-to-one propensity score matching (PSM) was conducted to compare progression-free survival (PFS) and overall survival (OS) between low and high SIRI patients. The discriminatory power of the combination of number of tumors and SIRI in predicting initial TACE response was evaluated by ROC analysis.ResultsPatients were divided into high SIRI (> 0.88) and low SIRI (≤ 0.88) groups. High SIRI (p = 0.003) and more than three tumors (p = 0.002) were significantly related to poorer tumor response. Moreover, the low SIRI group had longer PFS and OS than the high SIRI group (both P < 0.05) before and after PSM. Combination of SIRI and number of tumors can improve the predictive ability to predict initial TACE response with an area under the curve (AUC) of 0.678.ConclusionPretreatment peripheral blood SIRI was found to be an independent predictor of tumor response and clinical outcomes in patients with HCC undergoing TACE. Patients with high SIRI may have a poor prognosis.

Effects of transarterial chemoembolization on the immunological function of patients with hepatocellular carcinoma.

The present study aimed to investigate the effects of transarterial chemoembolization (TACE) on the immune function of patients with hepatocellular carcinoma (HCC). A total of 114 patients with HCC were selected and their peripheral blood was collected before and 1 month after TACE treatment. Flow cytometry and reverse transcription-quantitative PCR were performed to analyze the changes in immune function in patients before and after treatment. Kaplan-Meier curves were plotted for survival analysis. The programmed cell death ligand 1 (PD-L1) and programmed cell death protein 1 (PD1) expression before TACE treatment were significantly higher in patients with poor TACE response compared with those patients with well response. Higher PD-L1 mRNA expression in the peripheral blood mononuclear cells after TACE predicted a superior prognosis. After TACE treatment, the proportion of CD4+/CD8+ cells were decreased while the expression levels of programmed cell death protein 1 (PD1) were significantly increased. To conclude, TACE could reduce the proportion of CD4+/CD8+ cells and improve the mRNA expression levels of PD1 in patients with HCC. The expression levels of PD1 and PD-L1 were closely related to the therapeutic effect of TACE and the prognosis of patients with HCC. TACE combined with immunotherapy may have potential clinical value for patients with HCC.