Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality in Taiwan. The Taiwan Liver Cancer Association and the Gastroenterological Society of Taiwan had established a management ...consensus guideline in 2016. The current recommendations focus on updating critical issues regarding the management of HCC, including surveillance, diagnosis, and systemic treatment. For surveillance, the updated guideline suggests the role of dynamic computed tomography or magnetic resonance imaging and contrast-enhanced ultrasound (CEUS) in selected patients. For diagnosis, this update incorporates CEUS and recognizes the role of gadoxetic acid–enhanced magnetic resonance imaging. For systemic therapy, the updated guideline summarizes the multiple choices of targeted therapy, immune checkpoint inhibitors, and the combination of both. Through this update of the management consensus guideline, patients with HCC can benefit from receiving optimal diagnostic and therapeutic modalities.
The first edition of the guidelines for the use of ultrasound contrast agents was published in 2004, dealing with liver applications. The second edition of the guidelines in 2008 reflected changes in ...the available contrast agents and updated the guidelines for the liver, as well as implementing some nonliver applications. The third edition of the contrast-enhanced ultrasound (CEUS) guidelines was the joint World Federation for Ultrasound in Medicine and Biology-European Federation of Societies for Ultrasound in Medicine and Biology (WFUMB-EFSUMB) venture in conjunction with other regional US societies such as Asian Federation of Societies for Ultrasound in Medicine and Biology, resulting in a simultaneous duplicate on liver CEUS in the official journals of both WFUMB and EFSUMB in 2013. However, no guidelines were described mainly for Sonazoid due to limited clinical experience only in Japan and Korea. The new proposed consensus statements and recommendations provide general advice on the use of Sonazoid and are intended to create standard protocols for the use and administration of Sonazoid in hepatic and pancreatobiliary applications in Asian patients and to improve patient management.
OBP-301 is an oncolytic adenovirus modified to replicate within cancer cells and lyse them. This open-label, non-comparative, phase I dose-escalation trial aimed to assess its safety and optimal ...dosage in 20 patients with advanced hepatocellular carcinoma. Good tolerance was shown with a maximum tolerated dose of 6 × 1012 viral particles. The most common treatment-emergent adverse events were influenza-like illness, pyrexia, fatigue, decreased platelet count, abdominal distension, and anemia. Cohorts 4 and 5 had approximately 50% higher levels of CD8+ T cells in the peripheral blood after injection. The best target response occurred in 14 patients, 4 of whom had progressive disease. Multiple intratumoral injections of OBP-301 were well tolerated in patients with advanced hepatocellular carcinoma. The stable disease rate for the injected tumors was greater than the overall response rate, even with no obvious tumor response. OBP-301 might have a greater impact on local response as histological examination revealed that the presence of OBP-301 was consistent with the necrotic area at the injection site. Increased infiltration of CD8+ T cells and <1% PD-L1 expression were observed in tumors after injection. Improved antitumor efficacy might be achieved in future studies via viral injection with volume adjustment and in combination with other immuno-therapeutics.
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Heo and colleagues find that the stable disease rate for injected tumors was greater than overall response rate, and OBP-301 was well tolerated. OBP-301 injection modulates the tumor microenvironment. Despite multiple prior HCC therapies, patients had acceptable ECOG performance statuses and liver function.
Sarcopenia is an adverse prognostic factor in patients with liver cirrhosis and hepatocellular carcinoma (HCC). Image-based sarcopenia assessment allows a standardized method to assess abdominal ...skeletal muscle. However, which is an index muscle for sarcopenia remains unclear. Therefore, we investigated whether sarcopenia defined according to different muscle groups with computed tomography (CT) scans can predict the prognosis of HCC after radioembolization.
In this retrospective study, we analyzed patients who underwent radioembolization for unresectable HCC between January 2010 and December 2019. Before treatment, the total abdominal muscle (TAM), psoas muscle (PM), and paraspinal muscle (PS) areas were evaluated using a single CT slice at the third lumbar vertebra. In previous studies, sarcopenia was determined using the TAM, PM, and PS after stratifying by sex. Finally, we investigated each muscle-defined sarcopenia to decide whether or not it can serve as a prognostic factor for overall survival (OS).
We included 92 patients (74 men and 18 women). TAM, PM, and PS areas were significantly higher in the men than in the women (all
< 0.05). The patients with sarcopenia defined using PM, but not TAM and PS, exhibited significantly poorer OS than those without sarcopenia (median 15.3 vs. 23.8 months,
= 0.034, 0.821, and 0.341, respectively). After adjustment for clinical variables, such as body mass index, liver function, alpha-fetoprotein level, clinical staging, treatment response, and posttreatment curative therapy, PM-defined sarcopenia (hazard ratio: 1.899, 95% confidence interval: 1.087-3.315) remained an independent predictor for the poor OS.
CT-assessed sarcopenia defined using PM was an independent prognostic factor for the poorer prognosis of unresectable HCC after radioembolization.
Immune checkpoint inhibitors are groundbreaking resources for cancer therapy. However, only a few patients with hepatocellular carcinoma (HCC) have shown positive responses to anti-PD-1 therapy. ...Neoantigens are sequence-altered proteins resulting from somatic mutations in cancer. This study identified the neoantigens of Hep-55.1C and Dt81 Hepa1-6 HCCs by comparing their whole exome sequences with those of a normal C57BL/6 mouse liver. Immunogenic long peptides were pooled as peptide vaccines. The vaccination elicited tumor-reactive immune responses in C57BL/6 mice, as demonstrated by IFN-γ ELISPOT and an in vitro killing assay of splenocytes. In the treatment of three mouse HCC models, combined neoantigen vaccination and anti-PD-1 resulted in more significant tumor regression than monotherapies. Flow cytometry of the tumor-infiltrating lymphocytes showed decreased Treg cells and monocytic myeloid-derived suppressor cells, increased CD8+ T cells, enhanced granzyme B expression, and reduced exhaustion-related markers PD-1 and Lag-3 on CD8+ T cells in the combination group. These findings provide a strong rationale for conducting clinical studies of using neoantigen vaccination in combination with anti-PD-1 to treat patients with HCC.
•Neoantigen vaccination can notably enhance the antitumor effects of anti-PD-1 on mouse HCC.•Combination of neoantigen vaccination and anti-PD-1 elicits the most potent antitumor response and leads to better survival.•Combination treatment dramatically reshaped the tumor microenvironment than anti-PD-1 monotherapy group.•The results indicate that this combination therapy can be applied to treat patients with hepatocellular carcinoma.
The core needle biopsy (CNB), fine needle aspiration cytology (FNAC) and touch imprint cytology (TIC) are commonly used tools for the diagnosis of hepatic malignancies. However, little is known about ...the benefits and criteria for selecting appropriate technique among them in clinical practice. We aimed to compare the sensitivity of ultrasound-guided CNB, FNAC, TIC as well as combinations for the diagnosis of hepatic malignancies, and to determine the factors associated with better sensitivity in each technique.
From January 2018 to December 2019, a total of 634 consecutive patients who received ultrasound-guided liver biopsies at the National Taiwan University Hospital was collected, of whom 235 with confirmed malignant hepatic lesions receiving CNB, FNAC and TIC simultaneously were enrolled for analysis. The clinical and procedural data were compared.
The sensitivity of CNB, FNAC and TIC for the diagnosis of malignant hepatic lesions were 93.6%, 71.9%, and 85.1%, respectively. Add-on use of FNAC or TIC to CNB provided additional sensitivity of 2.1% and 0.4%, respectively. FNAC exhibited a significantly higher diagnostic rate in the metastatic cancers (P=0.011), hyperechoic lesions on ultrasound (P=0.028), and those with depth less than 4.5 cm from the site of needle insertion (P=0.036).
The sensitivity of CNB is superior to that of FNAC and TIC for the diagnosis of hepatic malignancies. Nevertheless, for shallow (depth <4.5 cm) and hyperechoic lesions not typical for primary liver cancers, FNAC alone provides excellent sensitivity.
The efficacy of treatment for advanced hepatocellular carcinoma (HCC) has remained limited. Polyinosinic–polycytidylic acid–poly-L-lysine carboxymethylcellulose (poly-ICLC) is a synthetic ...double-stranded RNA that serves as a viral mimic and induces an immune response. Intratumoral (IT) poly-ICLC injections can induce an autovaccination effect and prime the immune system, whereas intramuscular (IM) injection of poly-ICLC can attract and maintain tumor-specific cytotoxic T lymphocytes in tumors. We found that IT injection of poly-ICLC upregulated the expression of CD83 and CD86 on conventional type 1 dendritic cells in tumors. Combination therapy with IT followed by IM injections of poly-ICLC significantly inhibited tumor growth and increased the tumor-infiltrating CD8+ T cells in two syngeneic mouse models of HCC. Depletion of CD8+ T cells attenuated the antitumor effect. An IFN-γ enzyme-linked immunospot of purified tumoral CD8+ T cells revealed a significant proportion of tumor-specific T cells. Finally, the sequential poly-ICLC therapy induced abscopal effects in two dual-tumor models. This study provides evidence that the sequential poly-ICLC therapy significantly increased infiltration of tumor-specific CD8+ T cells in the tumors and induced CD8+ T cell–dependent inhibition of tumor growth, as well as abscopal effects.
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•Intratumoral injection of poly-ICLC into mouse HCC could activate cDC1 in the tumors.•Sequential poly-ICLC therapy increased infiltration of tumor-specific T cells in the tumors and induced antitumor effects.•The antitumor effects of sequential poly-ICLC therapy were CD8+ T cell-dependent.•Sequential poly-ICLC therapy could induce abscopal effects in two dual tumor models.
Learning Objectives:
After completing this course, the reader will be able to:
List the top 10 ranked symptoms after discharge suffered by patients with hepatocellular carcinoma (HCC) receiving ...transarterial chemoembolization (TACE) treatment.
Identify the significant factors in the associations between quality of life (QOL) and demographic factors and clinical factors over a period of 2 months in patients with HCC receiving TACE.
Design individualized education programs for newly diagnosed and recurrent HCC patients in order to maintain better QOL after treatment.
This article is available for continuing medical education credit at CME.TheOncologist.com
Objective.
To (a) explore changes in physical and psychological distress and quality of life (QOL) and (b) identify the significant pre‐ and postdischarge factors related to changes in physical and mental domains of QOL over a period of 2 months in patients with hepatocellular carcinoma receiving one course of transarterial chemoembolization (TACE) treatment.
Methods.
A longitudinal prospective design was used, with participants recruited from a teaching hospital in Northern Taiwan. Data were collected three times: within 3 days prior to discharge (T0) and at the fourth (T1) and eighth (T2) weeks after discharge. A set of structured questionnaires was used to assess participants' QOL, symptom distress, anxiety, and depression. Changes in QOL and associated factors were examined using generalized estimating equations.
Results.
Eighty‐nine patients were included in this study. Fatigue was reported to be the most distressful symptom after treatment. Overall QOL improved monthly after discharge. Change in physical QOL 2 months after TACE treatment was associated with age, diagnosis status, level of symptom distress, and depression after discharge. Change in mental QOL was significantly associated with gender, diagnosis status, and anxiety and depression after discharge.
Conclusions.
Health care providers should pay special attention to patients of older age, those who are male, and those who have higher levels of depression and anxiety after discharge. Designing personalized education programs before discharge for patients with newly diagnosed cancer versus those who have recurrent disease is suggested to help patients maintain a better QOL after discharge.
Changes in physical and psychological distress and quality of life were explored in patients with hepatocellular carcinoma receiving one course of transarterial chemoembolization treatment, and significant pre‐ and postdischarge factors related to changes in physical and mental domains of quality of life over a period of 2 months were identified.
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