Hepatocellular Carcinoma In Terms Research Articles

Applications of Yttrium-90 (90Y) in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, affecting millions of people worldwide. Due to the lack of systemic radiation therapy in hepatocellular carcinoma, researchers have been investigating the use of yttrium-90 (90Y) radioembolization for local-regional tumor control since the 1960s. With the development of glass and resin 90Y microspheres and the durable local control, good long-term efficacy, and equivalent tumor responsiveness and tolerability of 90Y-selective internal irradiation compared with alternative therapies such as transarterial chemoembolization (TACE) and sorafenib, 90Y radioembolization has gradually been applied in the treatment of hepatocellular carcinoma of all stages. In this article, we summarize the latest progress of 90Y in the treatment of hepatocellular carcinoma in terms of its principle, advantages, indications, contraindications, efficacy and adverse effects.

Evaluation of doxorubicin administrations in hepatocellular carcinoma in terms of genetic polymorphism, case study: Egypt

PurposeThis scientific article aims to evaluate the efficacy of the drug Doxorubicin for treating hepatocellular carcinoma (HCC) in Egypt. The study analyzes data from patients referred to a multi-disciplinary consultation at the National Cancer Institute, Cairo University. The study includes 40 intermediate-stage HCC patients who underwent treatment with either Doxorubicin-Lipiodol or Doxorubicin-loaded drug-eluting beads-trans-arterial chemoembolization (DEB-TACE).Design/methodology/approachPatients referred to a multi-disciplinary consultation at the National Cancer Institute, Cairo University with a possible diagnosis of HCC in the intermediate stage were eligible for the study.FindingsThe study finds that the plasma peak concentration of Doxorubicin is significantly higher in patients treated with Lipiodol compared to those treated with DEB-TACE. The median plasma peak concentration of patients treated with Lipiodol was significantly higher 424 (202.5–731) than the peak level of patients treated with beads 84.95 (26.6–156.5) with p-value = 0.036. However, there is no significant difference in other pharmacokinetic parameters between the two treatment groups. The research article also investigates the genetic polymorphisms in HCC patients treated with Doxorubicin-Lipiodol and Doxorubicin-loaded DEB-TACE. It identifies a significant association between the ABCB1 gene (C3435T) and the concentration of Doxorubicin in plasma. Patients with the CCand computed tomography (CT) genotypes of ABCB1 have higher concentrations of Doxorubicin compared to those with the TT genotype. Furthermore, the study examines the progression-free survival rates and tumour response in the two treatment groups. It demonstrates that DEB-TACE patients have a higher progression-free survival rate compared to cTACE patients. DEB-TACE also leads to better tumour regression.Originality/valueThe current study helps to increase the understanding of the genetic factors that may contribute to HCC susceptibility in the Egyptian population. However, it is essential to consider that genetic polymorphism is just one aspect of HCC risk, and other factors such as environment, lifestyle and viral infections also play crucial roles. Further research is needed to elucidate the complex interactions between genetic and environmental factors in HCC development among Egyptians.

Potential involvement of oncostatinM in the immunosuppressive tumor immune microenvironment in hepatocellular carcinoma with vessels encapsulating tumor clusters.

Vessels encapsulating tumor clusters (VETC) represents an adverse prognostic morphological feature of hepatocellular carcinoma (HCC), which is associated with an immunosuppressive tumor immune microenvironment (TIM). However, the underlying factors characterizing the TIM in HCC with a VETC pattern (VETC-positive HCC) remain uncertain. OncostatinM (OSM), a pleiotropic cytokine of the interleukin-6 family, regulates various biological processes, including inflammation, proliferation, and invasiveness of tumor cells. We aimed to test a hypothesis that OSM is associated with the immunosuppressive TIM of VETC-positive HCC. A total of 397 consecutive HCC patients with curative-intent hepatectomy were included. OSM-positive cells and inflammatory cells including CD4-, CD8-, CD163-, and FOXP3-positive cells were immunohistochemically evaluated. We compared VETC-positive and VETC-negative HCCs in terms of the number of these cells. We found the VETC pattern in 62 patients (15.6%). Our analysis revealed a significant decrease in the expression of arginase-1, a marker associated with mature hepatocyte differentiation, in VETC-positive HCC (p=0.046). The number of tumor-infiltrating OSM-positive cells was significantly low in VETC-positive HCC (p=0.0057). Notably, in VETC-positive HCC, the number of OSM-positive cells was not associated with vascular invasion, whereas in VETC-negative HCC, an increase in the number of OSM-positive cells was associated with vascular invasion (p=0.042). We identified an association between a decrease in OSM-positive cells and the VETC pattern. Additionally, our findings indicate that VETC-positive HCC is characterized by low hepatocyte differentiation and OSM-independent vascular invasion. These findings highlight the potential interaction between VETC-positive HCC cells and their TIM through the reduction of OSM-expressing cells.

Incidence trend and prognosis of intrahepatic cholangiocarcinoma: a study based on the SEER database.

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer after hepatocellular carcinoma (HCC). ICC and HCC have different cellular origins; therefore, ICC is significantly different from HCC in terms of aetiology, mechanism, tumour biological behaviour, treatment methods, and prognosis. The objective of this study was to investigate the current incidence trend and prognosis of ICC and deepen the understanding of ICC. A large sample of ICC and HCC patient data was obtained from the Surveillance, Epidemiology and End Results (SEER) database of the National Cancer Institute (NCI), USA. The incidence trend, prognosis, and the effect of surgery and lymph node dissection on the prognosis of ICC patients were analysed. In recent years, the incidence of ICC has increased. The treatment effect of ICC patients has been significantly improved. But the prognosis of ICC patients is significantly worse than that of HCC patients. Surgery can benefit all stages of ICC, and lymph node dissection is beneficial for the prognosis of patients with positive lymph nodes (N1). In recent years, the incidence of ICC has been increasing, and its prognosis remains poor, which is a cause for concern. We need to understand the epidemiological and pathophysiological characteristics of ICC and explore more effective treatment methods to improve the efficacy of treatment for ICC patients and prolong their survival.

Discovering pathway biomarkers of hepatocellular carcinoma occurrence and development by dynamic network entropy analysis

ObjectiveGene expression profiling techniques measure the transcription of thousands of genes in a parallel manner. With more and more hepatocellular carcinoma (HCC) transcriptomic data becoming available, the high-throughput data provides an unprecedented opportunity to discover HCC diagnostic biomarkers. In this work, we propose a bioinformatics method based on dynamic network entropy analysis, called DNEA, to identify potential pathway biomarkers for HCC occurrence and development by integrating transcriptome and interactome. MethodsWe firstly collect the pathways documented in different knowledge-bases and then impose the genome-wide human transcriptomic data of multistage cancerous tissues during the development and progression of HCC. After linking the gene sets of pathways into individual connected networks, we map the corresponding gene expression information onto these pathways. The dynamic network entropy of individual pathways is calculated to evaluate its activities and dysfunctionalities during the disease occurrence and development. We use the overall significant difference in the entropic dynamics during the time course to prioritize distinctive pathways during disease progression. Then machine learning classification methods are employed to screen out pathway biomarkers with the classification ability to distinguish different-stage samples of HCC progression. ResultsPathway biomarkers discovered based on DNEA demonstrate good classification performance in measuring HCC progression. The classification accuracy is as follows: DNA replication pathway (mean AUC = 0.82, 20 genes) from KEGG, FMLP pathway (mean AUC = 0.84, 14 genes) from BioCarta, and downstream signaling of activated FGFR pathway (mean AUC = 0.80, 15 genes) from Reactome. At the same time, previous studies have shown that these genes and pathways screened are closely related to the occurrence and development of HCC in terms of oncogenesis dysfunctions. ConclusionsOur method for cancer biomarker discovery based on dynamic network entropy analysis is effective and efficient in identifying pathway biomarkers related to the progression of complex diseases.

Efficacy and safety of frontline systemic therapy for advanced HCC: A network meta-analysis of landmark phase III trials

Direct comparisons across first-line regimens for advanced hepatocellular carcinoma are not available. We performed a network metanalysis of phase III of trials to compare first-line systemic treatments for hepatocellular carcinoma in terms of overall survival (OS), progression-free survival (PFS), objective response rate, disease control rate, and incidence of adverse events (AEs). After performing a literature review from January 2008 to September 2022, we screened 6,329 studies and reviewed 3,009 studies, leading to identification of 15 phase III trials for analysis. We extracted odds ratios for objective response rate and disease control rate, relative risks for AEs, and hazard ratios (HRs) with 95% CIs for OS and PFS, and used a frequentist network metanalysis, with fixed-effect multivariable meta-regression models to estimate the indirect pooled HRs, odds ratios, relative risks, and corresponding 95% CIs, considering sorafenib as reference. Of 10,820 included patients, 10,444 received active treatment and 376 placebo. Sintilimab+ IBI350, camrelizumab+ rivoceranib, and atezolizumab+ bevacizumab provided the greatest reduction in the risk of death compared with sorafenib, with HRs of 0.57 (95% CI 0.43-0.75), 0.62 (95% CI 0.49-0.79), and 0.66 (95% CI 0.52-0.84), respectively. Considering PFS, camrelizumab+ rivoceranib and pembrolizumab+ lenvatinib were associated with the greatest reduction in the risk of PFS events compared with sorafenib, with HRs of 0.52 (95% CI 0.41-0.65) and 0.52 (95% CI 0.35-0.77), respectively. Immune checkpoint inhibitor (ICI) monotherapies carried the lowest risk for all-grade and grade ≥3 AEs. The combinations of ICI+ anti-vascular endothelial growth factor, and double ICIs lead to the greatest OS benefit compared with sorafenib, whereas ICI+ kinase inhibitor regimens are associated with greater PFS benefit at the cost of higher toxicity rates. In the last few years, many different therapies have been studied for patients with primary liver cancer that cannot be treated with surgery. In these cases, anticancer drugs (alone or in combination) are given with the intent to keep the cancer at bay and, ultimately, to prolong survival. Among all the therapies that have been investigated, the combination of immunotherapy (drugs that boost the immune system against the cancer) and anti-angiogenic agents (drugs that act on tumoural vessels) has appeared the best to improve survival. Similarly, the combination of two types of immunotherapies that activate the immune system at different levels has also shown positive results. PROSPERO CRD42022366330.

Analysis on Efficacy of Hepatic Artery Infusion Chemotherapy with or without Lenvatinib for Unresectable Hepatocellular Carcinoma

Introduction: For patients with advanced hepatocellular carcinoma (HCC), hepatic artery infusion chemotherapy (HAIC) is a common and mature treatment, but the safety and efficacy of HAIC combined with lenvatinib for advanced HCC patient treatment remains unclear. Therefore, this study compared the safety and efficacy of HAIC with or without lenvatinib in unresectable HCC patients. Methods: We retrospectively analyzed 13 unresectable advanced HCC patients who received HAIC monotherapy or combination therapy of HAIC and lenvatinib. Overall survival (OS), disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), incidence of adverse events (AEs), and changes in liver function were compared between the two groups. We applied a Cox regression analysis to evaluate the independent risk factors affecting survival outcomes. Results: The ORR in the HAIC+lenvatinib group was markedly increased compared to the HAIC group (p < 0.05), while the DCR in the HAIC group was higher (p > 0.05). No notable difference was found between the two groups in median OS and PFS (p > 0.05). Compared to the HAIC+lenvatinib group, more patients had improved liver function in the HAIC group after treatment, but the difference was not dramatical (p > 0.05). The AEs incidence was 100.00% in both groups, which was relieved with corresponding treatment. Besides, Cox regression analysis did not identify independent risk factors related to OS and PFS. Conclusion: Combination therapy of HAIC and lenvatinib notably performed better than the HAIC monotherapy in patients with unresectable HCC in terms of ORR and was well tolerated, which deserves further investigation with large-scale clinical trials.

Macrophage GSK3β-deficiency inhibits the progression of hepatocellular carcinoma and enhances the sensitivity of anti-PD1 immunotherapy

BackgroundGlycogen synthase kinase 3β (GSK3β) was originally discovered to regulate glycogen synthesis and show a relationship to tumors. However, the biological functions of GSK3β in tumor-associated macrophages (TAMs) in cancers...

Nanobubbles containing PD-L1 Ab and miR-424 mediated PD-L1 blockade, and its expression inhibition to enable and potentiate hepatocellular carcinoma immunotherapy in mice

Immune checkpoint inhibitors (ICI) therapy is the main type of immunotherapy for cancer. Current clinical trials are focused on enhancing anti-tumor effects through combinations of multiple ICIs with agents that cause tumor cell death and release tumor antigens. In this study, weprepared nanobubbles (NBs) to load programmed death-ligand 1 (PD-L1) antibody andmiR-424gene to evaluate the combined anti-tumor activity of the targeted NBs.The miR-424 gene was chosen to be an anti-tumor gene, which can target PD-L1 and Bcl-2, through bioinformatics analysis and target gene verification. Then, PD-L1 Ab/miR-424-NBs were prepared by thin-film hydration. The optimal shape, size, and character of the NBs were determined by scanning electron microscopy and Zeta potential study. In addition, the antibody binding rate and gene loading of the targeted NBs were studied by agarose gel electrophoresis and flow cytometry, respectively. The synergistic immunotherapeutic effect of anti-PD-L1 antibody andmiR-424in vivo and their mechanism were evaluated using an H22 hepatoma transplanted tumor model in mice,whichproved that the targeted NBs mediated the PD-L1 antibody toblock the PD-1/PD-L1 signaling pathway and the transfected miR-424gene to downregulate the PD-L1 expression of tumor cells, both of which enhanced the antitumor immune effect mediated by T cells. It was also found that the targeted NBs activated T cells, which released a large number of cytokines, such as IFN-γ and IL-2, to recruit and activate macrophages and NK cells. It is suggested that ultrasound-mediated PD-L1 antibody NBs delivering miR-424 can inhibit the growth of subcutaneously transplanted hepatocellular carcinoma in terms of apoptosis and immunity. Therefore, ultrasound-mediated targeted NBs are a potential effective carrier for liver cancer, and PD-L1 antibody and miR-424 have a synergistic anti-tumor immunotherapy effect.

Evaluating the best treatment for multifocal hepatocellular carcinoma: A propensity score-matched analysis.

BACKGROUNDHepatocellular carcinoma (HCC) is a common tumour often diagnosed with a multifocal presentation. Patients with multifocal HCC represent a heterogeneous group. Although Trans-Arterial ChemoEmbolization (TACE) is the most frequently employed treatment for these patients, previous data suggested that liver resection (LR) could be a safe and effective procedure.AIMTo compare LR and TACE in patients with multifocal HCC in terms of procedure-related morbidity and oncologic outcomes.METHODSAll patients with multifocal HCC who underwent LR or TACE as the first procedure between May 2011 and March 2021 were enrolled. The decision to perform surgery or TACE was made after a multidisciplinary team evaluation. Only patients in Child-Pugh class A or B7 and stage B (according to the Barcelona Clinic Liver Cancer staging system, without severe portal hypertension, vascular invasion, or extrahepatic spread) were included in the final analysis. Propensity score matching was used to adjust the baseline differences between patients undergoing LR and the TACE group [number and diameter of lesions, presence of cirrhosis, alpha-fetoprotein (AFP) levels, and Model for End-Stage Liver Disease score]. The Kaplan-Meier method was used to estimate overall survival (OS) and disease-free survival (DFS). The outcomes of LR and TACE were compared using the log-rank test.RESULTSAfter matching, 30 patients were eligible for the final analysis, 15 in each group. Morbidity rates were 42.9% and 40% for LR and TACE, respectively (P = 0.876). Median OS was not different in the LR and TACE groups (53 mo vs 18 mo, P = 0.312), while DFS was significantly longer with LR (19 mo vs 0 mo, P = 0.0001). Subgroup analysis showed that patients in the Italian Liver Cancer (ITA.LI.CA) B2 stage, with AFP levels lower than 400 ng/mL, less than 3 lesions, and lesions bigger than 41 mm, benefited more from LR in terms of DFS. Patients classified as ITA.LI.CA B3, with AFP levels higher than 400 ng/mL and with more than 3 lesions, appeared to receive more benefit from TACE in terms of OS.CONCLUSIONIn a small cohort of patients with multifocal HCC, LR confers longer DFS compared with TACE, with similar OS and post-procedural morbidity.

A Case Report of Fibrolamellar Hepatocellular Carcinoma in a Young Adult

Among the four histopathological variants of hepatocellular carcinoma, Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare variant of hepatocellular carcinoma (HCC). It occurs in less than 1 % cases of hepatocellular carcinoma with distinct features as compared to classical HCC. It differs from typical HCC in terms of epidemiology, etiology, clinical presentation and prognosis. In this case report we are going to present a case of fibrolamellar variety of HCC in a 20-year young male with no history of previous liver disease and no characteristics features on Computed Tomography (CT) scan when compared with typical HCC. After discussing in multidisciplinary meeting, he underwent non anatomical liver resection which remained uneventful. Histopathology of the biopsy sample revealed FLHCC. No neoadjuvant therapy was given. Patient was kept on 1 year follow-up and no recurrence or metastasis occurred.

Suppressors of Cytokine Signaling and Hepatocellular Carcinoma.

Simple SummaryHepatocellular carcinoma (HCC) is a common malignancy worldwide. The HCC generally develops in the liver of patients already suffering from chronic liver disease. There have been significant advances in both the curative and palliative treatment of HCC. Although liver resection is a curative treatment for HCC, its indication is often limited due to an impaired liver function reservoir. There is still a need to understand how to control liver regeneration after resection and find better cancer immunotherapy and anticancer drugs for advanced HCC. Suppressors of cytokine signaling (SOCS) negatively regulate cytokine signaling related to cell proliferation, differentiation, and immune response; therefore, SOCS are thought to play an important role in HCC development and liver regeneration. Cytokines are secreted soluble glycoproteins that regulate cellular growth, proliferation, and differentiation. Suppressors of cytokine signaling (SOCS) proteins negatively regulate cytokine signaling and form a classical negative feedback loop in the signaling pathways. There are eight members of the SOCS family. The SOCS proteins are all comprised of a loosely conserved N-terminal domain, a central Src homology 2 (SH2) domain, and a highly conserved SOCS box at the C-terminus. The role of SOCS proteins has been implicated in the regulation of cytokines and growth factors in liver diseases. The SOCS1 and SOCS3 proteins are involved in immune response and inhibit protective interferon signaling in viral hepatitis. A decreased expression of SOCS3 is associated with advanced stage and poor prognosis of patients with hepatocellular carcinoma (HCC). DNA methylations of SOCS1 and SOCS3 are found in HCC. Precise regulation of liver regeneration is influenced by stimulatory and inhibitory factors after partial hepatectomy (PH), in particular, SOCS2 and SOCS3 are induced at an early time point after PH. Evidence supporting the important role of SOCS signaling during liver regeneration also supports a role of SOCS signaling in HCC. Immuno-oncology drugs are now the first-line therapy for advanced HCC. The SOCS can be potential targets for HCC in terms of cell proliferation, cell differentiation, and immune response. In this literature review, we summarize recent findings of the SOCS family proteins related to HCC and liver diseases.

Surgical Management of Early Hepatocellular Carcinoma

Abstract Background Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy ranking sixth in the world among all malignancies and becoming the third cause of death due to cancer. Incidence has increased all over the world, mainly because of increase in the incidence of chronic hepatitis B (HBV) and hepatitis C (HCV) infections Objective To study hepatocellular carcinoma in terms of pathogenesis, staging and diagnosis as well as discuss its surgical management and follow up afterwards. Patients and Methods Design: Prospective, comparative study. Setting: NHTMRI (national hepatology and tropical medicine research institute). Study duration: Period 3 years from April 2017 - April 2020. Patients: A total of 50 early HCC patients enrolled in the study. Results After applying (Forward method) and entering some predictor variables; the increase in operative time; had an independent effect on increasing ICU stay (p &amp;lt; 0.01). After applying (Forward method) and entering some predictor variables; the increase in age and operative time; had an independent effect on increasing drain removal days (p &amp;lt; 0.05 respectively). Conclusion Laparoscopic liver resection (LLR) is now considered a feasible alternative to open liver resection (OLR) in selected patients. Nevertheless studies comparing LLR and OLR are few and concerns remain about long-term oncological equivalence. LLR has short-term advantages and seemingly equivalent long-term outcomes and can be considered a feasible alternative to open surgery in experienced hands.

Exploring microsatellite instability in patients with advanced hepatocellular carcinoma and its tumor microenvironment.

Background and AimImmune checkpoint inhibitors and their combination with other agents have recently been available in advanced hepatocellular carcinoma (HCC). Hence, a thorough understanding of the tumor microenvironment based on tumor samples is yet to be achieved. This study aimed to explore the tumor microenvironment in advanced HCC in terms of microsatellite instability‐high (MSI‐H) by using tumor samples from advanced HCC patients eligible for systemic therapy.MethodsMSI‐H was assessed by polymerase chain reaction, and the expression of mismatch repair proteins, PD‐L1, CD8, VEGF, and HLA‐class1 was evaluated by immunohistochemistry. Whole‐exome sequencing was performed for MSI‐H tumor samples.ResultsOf 50 patients, one (2.0%) was confirmed with MSI‐H. In the MSI‐H advanced HCC tumor, a high tumor mutation burden, infiltration of CD8+ lymphocytes, and low expression of VEGF were identified. Although PD‐L1 expression was negative, there was shrinkage of tumor following pembrolizumab. However, another tumor nonresponsive to pembrolizumab was present simultaneously. Checking the Cancer Genome Atlas (TCGA) database, we found a similar case to this patient. The TCGA case had unique gene features of miR‐21 and miR‐155 overexpression and hypermethylation of the MSH2 gene.ConclusionWe identified a very small number of MSI‐H cases in HCC using one tumor biopsy sample for each patient with advanced HCC. In addition, epigenetic aberrations possibly lead to MSI‐H in HCC patients. Since different HCC clones might coexist in the liver, sampling from multiple tumors should be considered to clarify the true proportion of MSI‐H in HCC and to analyze tumor microenvironments.

Experimental Models of Hepatocellular Carcinoma-A Preclinical Perspective.

Simple SummaryHepatocellular carcinoma (HCC) is characterized by a broad molecular and genetic heterogeneity, which makes it a challenging subject in terms of the underlying mechanisms, response and resistance to treatment, and finding novel therapeutic options. Nowadays, new experimental models (3D in vitro models, in vivo mouse and non-mouse models, and computational studies) allow more detailed studies of hepatocellular carcinoma pathogenesis and treatment. Here, we provide insights into the current preclinical models frequently applied for the study of hepatocellular carcinoma.Hepatocellular carcinoma (HCC), the most frequent form of primary liver carcinoma, is a heterogenous and complex tumor type with increased incidence, poor prognosis, and high mortality. The actual therapeutic arsenal is narrow and poorly effective, rendering this disease a global health concern. Although considerable progress has been made in terms of understanding the pathogenesis, molecular mechanisms, genetics, and therapeutical approaches, several facets of human HCC remain undiscovered. A valuable and prompt approach to acquire further knowledge about the unrevealed aspects of HCC and novel therapeutic candidates is represented by the application of experimental models. Experimental models (in vivo and in vitro 2D and 3D models) are considered reliable tools to gather data for clinical usability. This review offers an overview of the currently available preclinical models frequently applied for the study of hepatocellular carcinoma in terms of initiation, development, and progression, as well as for the discovery of efficient treatments, highlighting the advantages and the limitations of each model. Furthermore, we also focus on the role played by computational studies (in silico models and artificial intelligence-based prediction models) as promising novel tools in liver cancer research.

Mechanistic Rationales Guiding Combination Hepatocellular Carcinoma Therapies Involving Immune Checkpoint Inhibitors.

Hepatocellular carcinoma (HCC) is one of the deadliest cancers because of late symptom manifestation leading to delayed diagnosis, which limits patients with HCC in terms of receiving curative surgical treatment. There are only a few therapeutic options for patients with advanced HCC. The emergence of immune checkpoint inhibitors (ICIs) brings HCC treatment to a stage at which nivolumab, an anti-programmed cell death protein 1 monoclonal antibody, achieves a 20% response rate. However, the large proportion of unresponsive patients drives the exploration of therapeutic strategies to improve ICIs' efficacy. Recent preclinical and clinical studies have suggested that ICIs, when used in combinations or when used with other cancer therapies, might elicit synergistic antitumor effects. However, the mechanistic rationales guiding different drug combinations to maximize this synergy remain largely ambiguous. In this review, we discuss different drug combinations used in HCC and the underlying mechanistic rationales, aiming to enhance the understanding of how these treatments can achieve synergy. This knowledge sets the foundation for the development of more effective and promising combination therapies for HCC.

Treatment outcomes of helical tomotherapy for hepatocellular carcinoma in terms of intermediate-dose spillage.

BackgroundAlthough helical tomotherapy (HT) tends to increase intermediate-dose spillage by increasing of low-dose region, this has not been fully determined in the clinical setting. Therefore, we investigated treatment outcomes of HT for hepatocellular carcinoma (HCC) with respect to intermediate-dose spillage.MethodsWe retrospectively reviewed 20 HCC patients, who received high-dose radiotherapy (RT) using HT with radical intent between April 2014 and September 2017. In accordance with the Barcelona Clinic Liver Cancer (BCLC) classification, stage was 0 in 7 patients, A in 3 patients, B in 5 patients, and C in 5 patients. Baseline Child-Pugh class was A in 18 patients and B in 2 patients. The median tumor size was 2.5 cm (range, 1–11 cm). Helical intensity-modulated radiotherapy (IMRT) technique was applied in all patients: among these, 13 patients were treated with stereotactic body radiotherapy (SBRT). The median fraction size was 12 Gy (range, 2–15 Gy), and the median total dose was 50 Gy (range, 44–60 Gy). Intermediate-dose spillage was assessed by the Radiation Therapy Oncology Group recommendation from 22 HT planning data, as follows: R50% means the ratio of the 50% prescription isodose volume to the planning target volume (PTV).ResultsThe median follow-up period after HT was 22 months. The local progression-free survival (LPFS) and progression-free survival (PFS) rates were 89% and 59% at 1 year, and 82% and 30% at 2 years, respectively. The overall survival rate was 100% at 1 year and 85% at 2 years, respectively. In terms of intermediate-dose spillage, minor or major deviations were noted in the R50% of 20 HT plans (91%). However, 1 patient (5%) experienced classic radiation-induced liver disease, and severe toxicity ≥ grade 3 was not reported.ConclusionsAlthough HT for HCC tends to increase intermediate-dose spillage, the treatment results were favorable with that reported in other published studies.

Predicting survival after liver transplantation in patients with hepatocellular carcinoma using the LiTES-HCC score

Liver transplant priority in the US and Europe follows the 'sickest-first' principle. However, for patients with hepatocellular carcinoma (HCC), priority is based on binary tumor criteria to expedite transplant for patients with 'acceptable' post-transplant outcomes. Newer risk scores developed to overcome limitations of these binary criteria are insufficient to be used for waitlist priority as they focus solely on HCC-related pre-transplant variables. We sought to develop a risk score to predict post-transplant survival for patients using HCC- and non-HCC-related variables. We performed a retrospective cohort study using national registry data on adult deceased-donor liver transplant (DDLT) recipients with HCC from 2/27/02-12/31/18. We fit Cox regression models focused on 5- and 10-year survival to estimate beta coefficients for a risk score using manual variable selection. We then calculated absolute predicted survival time and compared it to available risk scores. Among 6,502 adult DDLT recipients with HCC, 11 variables were selected in the final model. The AUCs at 5- and 10-years were: 0.62, 95% CI 0.57-0.67 and 0.65, 95% CI 0.58-0.72, which was not statistically significantly different to the Metroticket and HALT-HCC scores. The LiTES-HCC score was able to discriminate patients based on post-transplant survival among those meeting Milan and UCSF criteria. We developed and validated a risk score to predict post-transplant survival for patients with HCC. By including HCC- and non-HCC-related variables (e.g., age, chronic kidney disease), this score could allow transplant professionals to prioritize patients with HCC in terms of predicted survival. In the future, this score could be integrated into survival benefit-based models to lead to meaningful improvements in life-years at the population level. We created a risk score to predict how long patients with liver cancer will live if they get a liver transplant. In the future, this could be used to decide which waitlisted patients should get the next transplant.

Imaging Changes and Clinical Complications After Drug-Eluting Bead Versus Conventional Transarterial Chemoembolization for Unresectable Hepatocellular Carcinoma: Multicenter Study.

BACKGROUND. Drug-eluting bead transarterial chemoembolization (DEB-TACE) has emerged as an alternative to conventional TACE (cTACE) for treatment of hepatocellular carcinoma (HCC), although selection between the approaches remains controversial. OBJECTIVE. The purpose of this study was to compare DEB-TACE and cTACE in the treatment of patients with unresectable HCC in terms of hepatobiliary changes on imaging and clinical complications. METHODS. This retrospective study included 1002 patients (871 men, 131 women; mean age, 59 ± 12 years) from three centers who had previously untreated unresectable HCC and underwent DEB-TACE with epirubicin (780 procedures in 394 patients) or cTACE with ethiodized oil mixed with doxorubicin and oxaliplatin (1187 procedures in 608 patients) between May 2016 and November 2018. Among these patients 83.4% had hepatitis B-related liver disease, 57.6% had Barcelona Clinic Liver Cancer (BCLC) stage A or B HCC, and 42.4% had three or more nodules. Mean tumor size was 6.3 ± 4.2 cm. Hepatobiliary changes and tumor response were evaluated with CT or MRI 1 month after TACE. Clinical records were reviewed for adverse events. RESULTS. Bile duct dilatation (p < .001) and portal vein narrowing (p = .006) on imaging and liver failure (p = .03) and grade 3 abdominal pain (p < .001) in clinical follow-up occurred at higher frequency in the DEB-TACE group (15.5%, 4.6%, 2.3%, and 6.1%) than in the cTACE (7.4%, 1.6%, 0.7%, and 2.1%) group. Higher frequency of bile duct dilation in patients who underwent DEB-TACE was observed in subgroup analyses that included patients with BCLC stage A or B HCC (p = .001), with cirrhosis (p < .001), without cirrhosis (p = .04), and without main portal vein tumor thrombus (p = .002). Total bilirubin level 1 month after treatment was 1.5 ± 2.4 mg/dL (95% CI, 1.2-1.8 mg/dL) for DEB-TACE versus 1.3 ± 2.0 mg/dL (95% CI, 1.1-1.5 mg/dL) for cTACE (p = .02). The cTACE and DEB-TACE groups did not differ in other manifestations of postembolization syndrome or systemic toxicity (p > .05). Local tumor disease control rates did not differ between the cTACE and DEB-TACE groups (1 month, 96.7% vs 98.5%, p = .06; 3 months, 81.8% vs 82.4%, p = .87), but overall DCR was significantly higher in the cTACE than in the DEB-TACE group (1 month, 87.5% vs 80.0%, p = .001; 3 months, 78.5% vs 72.1%, p = .02). CONCLUSION. Compared with cTACE, DEB-TACE was associated with greater frequency of hepatobiliary injury and severe abdominal pain. CLINICAL IMPACT. Greater caution and closer follow-up are warranted for patients who undergo DEB-TACE for unresectable HCC than for those who undergo cTACE.

Dietary habits and risk of hepatocellular carcinoma among hepatitis B surface antigen carriers: A prospective cohort study in China.

In this prospective cohort study, we aimed to evaluate the association between dietary habits and the risk of developing hepatocellular carcinoma (HCC) in hepatitis B surface antigen (HBsAg)-positive carriers in Qidong, an hepatitis B virus (HBV)-epidemic area in China. A total of 3199 HBsAg carriers aged 30-70 years in a prospective cohort in Qidong, China from 2007 to 2011 were included in the study. At baseline, all participants self-reported their dietary habits in a questionnaire interview. A follow-up check-up was performed every 6 months to identify HCC cases until November 2017. Cox's regression analysis and an interaction analysis were performed to estimate the relative risks of HCC in terms of baseline diet. Among 3199 HBsAg-positive participants, 270 developed HCC (143.86/100 000 person-years [PYs]). Compared with participants who rarely consume garlic, the risk of HCC in those who consumed it ≥ once per week decreased along with the increase in frequency (HR = 1.00, 0.90 and 0.62 in those who consumed it rarely vs those who consumed it 1-6 times per week and ≥ 7 times per week, respectively). This study found a synergistic effect between garlic and tea consumption on the risk of HCC (P = 0.039 for a multiplicative interaction). HBsAg carriers should improve their diet. Regular consumption of garlic and tea drinking may reduce the HCC incidence in HBsAg carriers.