Intermediate Stage HCC Research Articles

Capitalizing on Success of Systemic Therapy to Improve Outcomes of Intermediate-Stage HCC.

Capitalizing on Success of Systemic Therapy to Improve Outcomes of Intermediate-Stage HCC.

SY26-3 Systemic chemotherapy for intermediate-stage hepatocellular carcinoma

Currently, 6 regimens are available for systemic chemotherapy for hepatocellular carcinoma. While it is significant that treatment options for advanced-stage HCC have expanded, it is also significant that the treatment strategy of the intermediate-stage (BCLC stage B) HCC which targets TACE has been changed. In particular, it is no exaggeration to say that lenvatinib has significantly changed the treatment strategy for the Intermediate stage. BCLC stage B is defined as follows; Child-Pugh A-B liver function and intrahepatic multiple tumors without vascular invasion or extrahepatic spread. Conventionally, TACE has been recommended for treatment of this stage. However, it has long been pointed out that this BCLC stage B is a heterogeneous tumor status that includes various tumor conditions, such as liver function (Child-Pugh score 5-7) and tumor burden (Up to 7 IN/OUT). Subclassification has been attempted using liver function, tumor burden and treatments have been subdivided for each substage. For BCLC stage B1 (Up-to-7 IN and Child-Pugh score 5-7), surgical resection or radiofrequency ablation (RFA) according to BCLC stage A, and super-selective lipiodol-TACE for curative intent is recommended. On the other hand, for BCLC StageB2 (Up-to-7 OUT and Child-Pugh score 5-7), molecular targeted therapy (MTT) is recommended instead of TACE. In particular, lenvatinib can achieve the downstaging by its higher tumor shrinkage effect and convert to curative treatment such as surgical resection, RFA or TACE. Also, lenvatinib is less likely to worsen hepatic reserve than TACE. The treatment strategy for BCLC stage B in which TACE was a standard of care is now changing dramatically by emergence of MTT. It is important to select the optimal treatment according to the tumor status with keeping in mind the preservation of liver function. It is significant that molecular-targeted agents have expanded the range of treatment options for intermediate-stage HCC.

REPLACEMENT trial in progress: Combination therapy with atezolizumab plus bevacizumab for TACE unsuitable patients with beyond up-to-seven criteria in intermediate stage hepatocellular carcinoma: A phase II study.

TPS4162 Background: Transarterial chemoembolization (TACE) had been developed as a standard of care in patients with intermediate-stage HCC at a time when systemic therapy was not available. This stage includes a certain TACE-unsuitable subpopulation, such as beyond up-to-seven criteria. Recently, the American Association for the Study of Liver Diseases and Asia-Pacific Primary Liver Cancer Expert Meeting have recommended systemic therapy for those patients to achieve overall survival (OS) beyond 2 years without impaired liver function in their consensus guideline. However, there is not enough data on systemic therapy for this population. Atezolizumab (Atezo), anti-PD-L1 antibody, plus Bevacizumab (Bev), anti-VEGF antibody, combination therapy has been shown to significantly improve OS, progression-free survival (PFS), and overall response rate (ORR) against sorafenib, which is a standard of care in unresectable HCC according to a phase III randomized controlled trial, IMbrave150. Therefore, we investigate the efficacy and safety of Atezo+Bev combination therapy in patients with HCC beyond up-to-seven criteria in this trial. Methods: REPLACEMENT trial is a multicenter, single-arm phase II study of Atezo+Bev combination therapy. Key eligibility criteria are age ≥20 years, ECOG performance status 0-1, Child-Pugh A, no vascular invasion, no extrahepatic metastasis, beyond up-to-seven criteria, and patients who have received neither systemic therapy nor TACE. Patients will be administrated Atezo 1200 mg/body + Bev 15 mg/kg once every 3 weeks. The primary endpoint is PFS per modified RECIST (mRECIST). The secondary endpoints include PFS, ORR, duration of response (DOR) per mRECIST; PFS, ORR, DOR per RECIST ver.1.1; OS and safety including change of liver function based on albumin-bilirubin (ALBI) score until disease progression. A total of 60 events are necessary to investigate the hypothesis that a target point estimation of PFS rate at 6 months (null population: 55%, alternative population: 73%). The estimated sample size is, therefore, 70 patients. In addition, the results of the Atezo+Bev therapy in this arm will be compared with those in approximately 600 TACE treated consecutive patients with intermediate-stage HCC, using the propensity score matching method, as an exploratory analysis of a possible replacement of TACE by the Atezo+Bev therapy. Patients’ enrollment had already started in December 2020, and 12 patients were enrolled as of 16th February ’21. Clinical trial information: jRCTs071200051.

Abstract No. 117 A phase 3, double-blind, randomized study of nivolumab and Ipilimumab), nivolumab monotherapy, or placebo plus transarterial chemoembolization in patients with intermediate-stage hepatocellular carcinoma

TACE is the most widely used locoregional therapy recommended for patients with intermediate-stage HCC (Barcelona Clinic Liver Cancer stage B). Despite the significant tumor responses that can be achieved with TACE, tumors commonly recur, progress, or are refractory. Clinical trials have explored the combination of TACE with tyrosine kinase inhibitors; however, these have not reported improved outcomes. HCC possesses a unique immunosuppressive microenvironment, which makes it an attractive target for immunotherapies, particularly immune checkpoint inhibitors.

Prospective, multicenter study of apatinib combine with TACE in treating intermediate to advanced stage HCC patients: A real-world study from China.

282 Background: Combination of transcatheter arterial chemoembolization (TACE) with apatinib are emerging as an effective treatment for patients with intermediate to advanced stage HCC. However, the data of HCC treated by apatinib in the real-world setting are not reported. In this real-world study, we aimed to explore the efficacy and safety of HCC pts which underwent TACE combine with apatinib. Methods: This was a prospective, multicenter observational study in a real-world setting and this study was approved by our Ethics Committee. Pts aged ≥18 years with well diagnosed intermediate or advanced stage HCC were included. The pts received apatinib plus TACE treatment as the first-line therapy. TACE treatment was performed on demand, the dose of apatinib was selected by the investigator. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival rate (OS), objective response rate (ORR), disease control rate (DCR) and safety profile. All of the objective response was assessed by independent central review per mRECIST criteria. Results: From Jun 2019 to Feb 2020, a total of 98 well diagnosed HCC pts with age from 31 to 86 were enrolled in this study. As of August 2020, the median follow-up was 9.5 months. The mPFS of 98 pts was 7 months. The ORR, DCR and 6 months OS rate was 35.7%, 76.5% and 82.6%, respectively.The PFS was 7.5 months in intermediate stage and 6.4 months in advanced stage. The ORR was 46.3% in intermediate stage (41 cases) and 28% in advanced stage (57 cases) HCC. And the 6 months OS rate was 90.2% in intermediate stage and 77.1% in advanced stage HCC. Overall, 17 (17.3%) pts had grade≥3 treatment-related AEs. All of the safety adverse effects can be tolerated or reduced after symptomatic treatment and no unexpected adverse events were observed. Conclusions: In this real-world study, apatinib showed a favorable efficacy and safety profile in pts with intermediate and advanced stage cancer. Apatinib combination TACE therapy might lead to better survival benefit in first-line treatment for HCC pts. Clinical trial information: ChiCTR1900024030.

P-241 First- and second-line treatment with tyrosine kinase inhibitors after chemoembolization in intermediate-stage hepatocellular carcinoma patients

The benefits of sorafenib as first-line treatment and regorafenib as second-line treatment for HCC patients after recurrence to TACE is not yet adequately studied. Aim: To estimate the efficacy of sorafenib as first-line treatment and regorafenib as second-line treatment in patients with intermediate-stage HCC after recurrence to previous TACE treatment. Retrospectively, we estimated the efficacy of sorafenib and regorafenib administration (overall survival [OS] and time to disease progression [TTDP]) in 12 patients (Group A) with intermediate-stage HCC after recurrence to treatment with TACE (1-3 TACEs; median, 2). The results were compared with those of a similar historical group of 15 HCC patients treated only with TACE (Group B). There were no significant differences in disease characteristics between the two studied groups. The index of disease control for group A was 67.2% and the mean TTDP was 4.2 months during sorafenib administration. Regorafenib was administered when progression of HCC was observed. The OS was 31.2 months. For Group B, the index of disease control was 30.6% (P = .001), the mean TTDP was 2.3 months (hazard ratio, 0.44; Ρ < .01), and the OS was 13.4 months (hazard ratio, 0.57; Ρ < .001). The multivariate analysis revealed that the addition of sorafenib and regorafenib was the most important factor for OS and the prolongation of the TTDP. The administration of sorafenib and regorafenib seems to be an attractive therapeutic approach for patients with intermediate-stage HCC after recurrence to previous TACE treatment.

Nonsurgical management of advanced hepatocellular carcinoma: a clinical practice guideline.

Practice guidelines based on a systematic review of the literature regarding the nonsurgical management of hepatocellular carcinoma (hcc) in North America are lacking. Resection and transplantation are the foundations for cure of hcc; however, most patients are diagnosed at an advanced stage, precluding those curative treatments. A number of local or regional therapies are used and are followed by systemic therapy for advanced or progressive disease. Other treatments are available, but their efficacy, compared with those standards, is not well known. First, systematic review questions were developed. Literature searches of the medline, embase, and Cochrane library databases (January 2000 to July 2018 or January 2005 to July 2018 depending on the question) were conducted; in addition, abstracts from the 2018 annual meeting of the American Society of Clinical Oncology were reviewed. A practice guideline was drafted that was then scrutinized by internal and external reviewers. Seventy-seven studies were included in the guideline: no guidelines, two systematic reviews, and seventy-five primary studies published in full (including one pooled analysis). Five recommendations were developed. There is no evidence for or against the use of local or regional interventions other than transarterial chemoembolization for the treatment of intermediate- or advanced-stage hcc. Furthermore, there is no evidence to support the addition of sorafenib to any local or regional therapy. Sorafenib or lenvatinib are recommended for first-line systemic treatment of intermediate-stage hcc. Regorafenib or cabozantinib provide survival benefits when given as second-line treatment. Antiviral treatment is recommended in individuals with advanced hcc who are positive for the hepatitis B surface antigen.

Nivolumab in Combination With TACE for Patients With Intermediate Stage HCC

Nivolumab in Combination With TACE for Patients With Intermediate Stage HCC

Initial lenvatinib therapy with no prior TACE in patients with intermediate-stage hepatocellular carcinoma beyond up-to-seven criteria and Child-Pugh A liver function: A proof-of-concept study.

522 Background: Intermediate-stage HCC is a heterogenous population with subgroups of patients that do not benefit from TACE. Hence, we conducted a matched cohort study to compare the efficacy of lenvatinib to TACE in intermediate-stage HCC patients with large or multinodular tumours exceeding the up-to-7 criteria. Methods: This study first identified 642 consecutive patients with HCC initially treated with lenvatinib or conventional TACE (cTACE) between January 2006 and December 2018. Of these patients, 176 who received lenvatinib or cTACE as an initial treatment and met the eligibility criteria [unresectable, beyond the up-to-7 criteria, without prior TACE/systemic therapy, no vascular invasion, no extrahepatic spread and Child-Pugh A liver function] were selected. Propensity score matching was used to adjust for patients’ demographics. Results: After propensity-score matching, outcome of 30 patients prospectively treated with lenvatinib (14 in clinical trials [1 Phase II and 13 Phase III REFLECT trial], 1 in early access program and 15 in real world setting) and 60 patients treated with cTACE as the initial treatment was compared. The lenvatinib group showed a higher objective response rate (73.3% vs. 33.3%; p &lt; 0.001) and longer median progression-free survival than the cTACE group (16.0 vs. 3.0 months; p &lt; 0.001). Median overall survival was also significantly longer in the lenvatinib group than in the cTACE group (37.9 vs. 21.3 months; hazard ratio: 0.48, p &lt; 0.01). The change of ALBI score from baseline to the end of treatment were -2.61 to -2.61 for 30 patients in lenvatinib group (p = 0.254) and -2.66 to -2.09 in cTACE group (p &lt; 0.01), respectively. Conclusions: In patients with large or multinodular intermediate-stage HCC exceeding the up-to-7 criteria with Child-Pugh A liver function, who usually do not benefit from TACE, lenvatinib is associated with better outcome than TACE. In particular, leventinib is associated with preservation of hepatic function during treatment while TACE is associated with deterioration of hepatic function.

The efficacy and safety of lenvatinib in patients with intermediate-stage hepatocellular carcinoma: A nationwide multicenter study in Japan.

548 Background: Lenvatinib (LEN) has been used in patients with unresectable hepatocellular carcinoma (u-HCC) since Mar 2018 in Japan. We conducted a nationwide multicenter study and especially focused on the efficacy and safety in the patients with intermediate-stage u-HCC. Methods: A total of 240 patients received LEN from March 2018 at 15 sites in Japan was enrolled. Tumour assessments in accordance with modified RECIST were done using dynamic CT or MRI within 4-8 weeks and every 6-8 weeks thereafter. Results: In this study, 88 of 240 (36.7%) patients were BCLC stage B. Among them 76 (86.3%) patients received TACE before LEN and the median number of TACE was 2 (1-10). Only 4 patients were TKI experienced and other 84 (95.5%) patients received LEN as a 1st line therapy. The median pretreatment ALBI score was -2.35 and 75 (85.2%) patients were Child-Pugh A. In this cohort, 73 (83.0%) patients were beyond up-to-seven criteria and the median pretreatment AFP was 38.2 (2-12870) ng/mL. The median observation time was 8.5 months and 16 patients died. The median progression free survival was 8.7 months, and the median overall survival (OS) was not reached. Objective response rate (ORR) and disease control rate (DCR) were 48.5% and 80.3%. AFP decrease ( &gt; 20%) after 1 month was observed in 52 (59.0%) patients. Child-Pugh B patients (n = 13) had significantly shorter OS than Child-Pugh A (p = 0.02) and median OS in Child-Pugh B patients was 8.8 months. The patients received &gt; 6 times TACE before LEN had significantly shorter OS than patients received ≤ 6 times TACE (p = 0.02). Additional TACE was performed in 8 patients and The median time of restarting LEN was 19 days. The median ALBI score before additional TACE, Day 1 after TACE and Day 28 after TACE were -2.38, -2.07, and -2.36.There was no severe adverse event associated with additional TACE. The median duration of LEN in patients treated with LEN and additional TACE was 8.5 months. Conclusions: The ORR and DCR of LEN in Child-Pugh A patients with intermediate-stage HCC were 46.6% and 79.3%. The therapeutic strategies for intermediate-stage HCC should be discussed based on the liver function, tumor states, and treatment course about TACE.

The Current Landscape of Systemic Therapies for Advanced Hepatocellular Carcinoma

As the global burden of HCC continues to rise, there is an overwhelming need for new systemic therapies for the treatment of advanced-stage HCC. In this review, we explore the current landscape of approved therapies for intermediate-stage HCC after progression with locoregional therapy or in those who present with advanced-stage HCC not amenable to curative options. In the last 10 years, several agents have been studied in the first and second-line treatment of HCC but failed to show clinical benefit. Between 2008 and 2016, sorafenib was the sole agent used in the treatment of advanced-stage HCC. Recent strides have shown success with lenvatinib as an alternative agent for first-line treatment, and regorafenib, cabozantinib, ramucirumab, nivolumab, and pembrolizumab as second- and thrid-line agents in advanced HCC. The next series of HCC trials are appropriately directed at combination therapies—combining targeted therapy with immunomodulators in the hopes of improving overall survival and ultimately getting closer to finding a cure.

PCN510 HEALTHCARE RESOURCE UTILISATION (HCRU) ASSOCIATED WITH TRANSCATHETER ARTERIAL CHEMOEMBOLISATION (TACE) TREATMENT IN INTERMEDIATE STAGE HEPATOCELLULAR CARCINOMA (HCC) PATIENTS IN EUROPE

TACE is the standard-of-care first line treatment for intermediate stage HCC patients. Despite its routine use in this patient population, there is limited evidence regarding the direct HCRU. This study explores the resource impact to healthcare systems of TACE in Europe. A cross-sectional study was conducted in EU5 from January to May 2019. Interventional radiologists and radiation oncologists completed case report forms (CRFs) for patients classified as Stage B2 or B3 based on Barcelona Liver Cancer Clinic (BCLC) and Kinki subclassification criteria. Patients must have received TACE within 30 days of data capture. CRFs captured direct HCRU associated with each TACE. 317 CRFs were collected from 59 physicians. Median patient age was 65 years (range: 36-90), 70% were male, and 23% patients had hepatitis C. At data capture, 72% were Kinki criteria stage B2; 26% were B3. 39% patients had an ECOG score 0 versus 61% score 1; 82% were Child Pugh B class. Most (70%) received TACE as first HCC treatment. During first procedure, 72% patients received conventional TACE (28% DEB-TACE), predominantly as inpatients (81%), with a mean hospital stay of 3.7 days. Following TACE, 15% patients had an unplanned hospitalization, attributed to post-embolization syndrome in 40% of cases. Mean inpatient duration was an additional 3.5 days, with 12% patients admitted to intensive care. 32% patients received TACE as combination therapy. Since first TACE, patients received a mean 11.9 tests, including liver and kidney function tests and scans. Patients consulted HCPs a mean 4.4 times. HCRU burden of TACE therapy is considerable, with most patients requiring multiple days of hospitalization to administer or manage the effects of treatment, and a high demand on additional resources to monitor the clinical impact. There is a clear unmet need for treatments to minimize the disease burden in intermediate stage HCC.

122O - Should transarterial chemoembolization be continued after non-response to the first two sessions for intermediate-stage hepatocellular carcinoma?

BackgroundCurrent guidelines recommend that two transarterial chemoembolization (TACE) should be performed before switching to another treatment for intermediate-stage HCC, but without robust evidence. Considering the paucity of effective subsequent treatments after TACE-refractoriness, we aimed to evaluate radiologic response of HCC to the third TACE (TACE-3) after nonresponse (stable disease (SD) or progressive disease (PD)) to the first two sessions, and to establish a nomogram to predict responders to TACE-3. MethodsThe study enrolled 1672 intermediate-stage HCC patients with Child-pugh A liver function (training cohort: n = 918; internal validation cohort: n = 460; external validation cohort: n = 294) who did not respond to (based on mRECIST) the first two TACE but underwent ≥3 consecutive TACE from three centers. Radiologic response rate to TACE-3 and its correlation with overall survival (OS) was evaluated. Nomogram predicting responders to TACE-3 was established and validated. ResultsFor patients with SD after the first two TACE, the response rate after TACE-3 was 44.4% in training and internal validation cohorts and 51.5% in external validation cohort. For patients with PD, corresponding rates were 2.7% and 2.2%. Responders to TACE-3 achieved higher 5-year OS rates than non-responders in three cohorts (all P < 0.001). Radiologic response to TACE-3 (HR = 0.151, 95% CI: 0.117-0.195, P < 0.001) was the strongest prognostic factor of OS. The C-index of nomogram, constructed by tumor size, tumor capsule and alpha-fetoprotein, was 0.835 (95% CI: 0.810, 0.861) in training cohort, 0.853 (95% CI: 0.819, 0.887) in internal validation cohort and 0.846 (95% CI: 0.825, 0.892) in external validation cohort. ConclusionsApproximately 50% of patients with SD could respond to TACE-3 with improved survival whereas patients with PD barely could. Our nomogram is effective in predicting responders to TACE-3. Legal entity responsible for the studyThe First Affiliated Hospital of Sun Yat-sen University. FundingThe National Natural Science Foundation of China (No. 81801703), the Guangdong Natural Science Foundation of Guangdong Province (No. 2018A030310282), the National high level talents special support plan--“Ten thousand plan"--Young top-notch talent support program, the National Science Fund for Distinguished Young Scholars (No. 81825013). DisclosureAll authors have declared no conflicts of interest.

Update on transarterial approaches to locoregional treatment in hepatocellular carcinoma.

This review explores current knowledge and recent data about vascular-centered locoregional treatments and proposes alternate algorithms. Hepatocellular carcinoma represents the sixth most common neoplasm worldwide. Currently, the Barcelona Clinic Liver Cancer (BCLC) staging is the most commonly used in Europe for treatment allocation. According to this classification, European Society for Medical Oncology (ESMO) guidelines currently recommend transarterial chemoembolization for intermediate stage HCC and systemic treatments, such as, sorafenib in more advanced stages. However, strong evidences are still lacking to conclude to the superiority of one technique over another, as the optimal treatment choice remains challenging and should take into consideration more clinical, biological and imaging findings than reported in the BCLC staging system, such as patient age or clinical status, tumor characteristics (including distribution and heterogeneity), tumor vascularization and concomitant portal hypertension or biliary anomalies. Many controversies remain, in particular, the relative place of bland embolization versus chemoembolization, the clinical benefit of drug-eluting bead chemoembolization (DEB-TACE) over conventional chemoembolization (cTACE), as well as the real place of radioembolization in general setting as well as innovative applications, such as radiation segmentectomy and radiation lobectomy.

Sa1588 – Retrospective Comparison of the Safety and Efficacy of Selective Internal Radiation Therapy (With Yttrium-90 Microspheres) Versus Transarterial Chemoembolization As First-Line Treatment for Intermediate Stage Hcc

Sa1588 – Retrospective Comparison of the Safety and Efficacy of Selective Internal Radiation Therapy (With Yttrium-90 Microspheres) Versus Transarterial Chemoembolization As First-Line Treatment for Intermediate Stage Hcc

Comparing stereotactic ablative radiotherapy (SABR) versus re-trans-catheter arterial chemoembolization (re-TACE) for hepatocellular carcinoma patients who had incomplete response after initial TACE (TASABR): a randomized controlled trial

BackgroundHepatocellular carcinoma (HCC) accounts for 75–85% of primary liver cancers and is prevalent in the Asia-Pacific region. Till now, trans-arterial chemoembolization (TACE) is still one of common modalities in managing unresectable intermediate-stage HCC. However, post-TACE residual viable HCC is not uncommon, resulting in unsatisfied overall survival after TACE alone. Recently, stereotactic ablative radiotherapy (SABR) has been suggested to manage HCC curatively. However, evidence from phase-III trials is largely lacking.Hence, the present phase III randomized trial is designed to compare clinical outcomes between SABR and re-TACE for unresectable HCC patients who had incomplete response after initial TACE.MethodsThe present study is an open-label, parallel, randomized controlled trial. A total of 120 patients will be included into two study groups, i.e., SABR and re-TACE, with a 1:1 allocation rate. A 3-year allocating period is planned. Patients with incomplete response after initial TACE will be enrolled and randomized. The primary endpoint is 1-year freedom-form-local-progression rate. Secondary endpoints are disease-progression-free survival, overall survival, local control, response rate, toxicity, and duration of response of the treated tumor.DiscussionSABR has been reported as an effective modality in managing intermediate-stage HCC patients, but evidence from phase-III randomized trials is largely lacking. As a result, conducting randomized trials to demarcate the role of SABR in these patients is warranted, especially in the Asia-Pacific region, where HBV- and HCV-related HCCs are prevalent.Trial registrationBefore enrolling participants, the present study was registered prospectively on ClinicalTrials.gov (trial identifier, NCT02921139) on Sep. 29, 2016. This study is ongoing.

03:45 PM Abstract No. 378 Establishment of hepatocellular carcinoma patient-derived xenografts from minimally invasive image-guided percutaneous biopsies

The generation of patient derived xenografts (PDXs) from core needle biopsies of intermediate and advanced stage HCC patients who are not candidates for resection is technically challenging due to the small quantities of tumor tissue obtained. Further complicating PDX generation is the high rate of EBV infection in humans (>90%) and the presence of EBV-transformed B lymphocytes in HCC samples, which grow opportunistically in immunocompromised mice to yield EBV-associated lymphomas at the expense of HCC xenografts. We sought to identify methodological improvements in PDX generation that mitigate the formation of lymphocytic PDXs and improve the efficiency of HCC-xenograftment. As part of an ongoing observational clinical trial of subjects with HCC, ultrasound-guided percutaneous biopsies were obtained from treatment-naïve patients. Entire biopsy samples were subcutaneously engrafted into immunodeficient mice using either basement membrane matrix (Matrigel) or PBS as an inoculation substrate. Tumor growth was monitored and mice were euthanized for necropsy when tumors reached a threshold size. Immunohistochemistry and in-situ hybridization (ISH) was done on explanted xenografts to examine the expression of immune cell (CD3, CD20, CD45), HCC/hepatocholangiocarcinoma (AFP, albumin, CK7, HNF4a), and EBV (EBV-encoded RNA; EBER1)-associated molecular markers. Xenografts arising from biopsies implanted without Matrigel uniformly expressed the immune cell marker CD45, whereas xenografts implanted with Matrigel did not (N=9 biopsies from 5 patients that resulted in xenograft). Further characterization with human-CD3/CD20 co-staining and ISH for EBER1 showed that these tumors were consistent with EBV driven B-cell lymphomas. Only in xenografts implanted with matrigel did we see expression of AFP, albumin, CK7, or HNF4a. These data suggest that minimally invasive percutaneous liver biopsies can be used with relatively high efficiency to generate patient derived xenografts for the two most common primary liver cancer subtypes and that this process may be augmented by the addition of Matrigel during the implantation process.

Immunohistochemistry Detects Increased Expression of Aldo-Keto Reductase Family 1 Member B10 (AKR1B10) in Early-Stage Hepatocellular Carcinoma.

BackgroundHepatocellular carcinoma (HCC) remains difficult to diagnose at an early stage. Aldo-keto reductase family 1 member B10 (AKR1B10) is an oxidoreductase that is upregulated in some chronic liver diseases. The aim of this study was to use immunohistochemistry to evaluate the expression of AKR1B10 in liver tissue from patients with HCC of different stages.Material/MethodsForty-four patients with a tissue diagnosis of HCC (35 males and 9 females) with 37 control samples of liver tissue containing liver cirrhosis were studied using immunohistochemistry for the expression of AKR1B10. Histological examination determined the grade of HCC; the stage of HCC was determined according to the Barcelona Clinic Liver Cancer (BCLC) staging system. Serum alpha-fetoprotein (AFP) levels were measured and compared between the patients with HCC.ResultsImmunohistochemistry showed increased expression of AKR1B10 in moderately-differentiated HCC compared with well-differentiated HCC, poorly-differentiated HCC, and liver cirrhosis (P<0.05). Sensitivity and specificity of AKR1B10 expression in HCC were high at a cutoff integral optical density (IOD) value of 89.5. A significant increase in AKR1B10 expression was found in early-stage HCC (P<0.05). Serum AFP levels were increased in patients with poorly-differentiated HCC, were increased in intermediate-stage HCC, and were significantly increased in advanced-stage HCC (P<0.05).ConclusionsImmunohistochemistry showed that the expression of AKR1B10 was increased in tumor tissue from patients with early-stage HCC. Further studies are needed to determine the role of AKR1B10 in the early detection of HCC.

Surgical resection for BCLC intermediate stage hepatocellular carcinoma: a comparison with early or very early stage hepatocellular carcinoma

Introduction: Despite BCLC guideline, many patients with intermediate stage HCC undergo surgical resection in Japan. Methods: Retrospective single-institutional analysis of was performed in patients who underwent initial radical surgery for HCC between October 1994 and December 2015. They were classified into 4 groups. A: Early or Very early stage (n = 606). B1: Solitary and > 5 cm (n = 198). B2: 2-3 tumors and < 3 cm (n = 158). B3: 4 or more tumors (n = 68). Long term results were analyzed. Results: In group A, 296 Pts (49%) had solitary tumor. In group B1, the median tumor size was 7.2 cm. In group B2, 119/39 Pts had 2/3 tumors. In group B3, 31/11/7/19 Pts had 4/5/6/7- tumors, respectively. 5-year overall survival was 71.7％ in group A, 63.7％ in group B1, 52.4％ in group B2, and 36.8％ in group B3, where statistically significant differences were seen between B1 and B2, B2 and B3, although no significant difference was seen between A and B1 (HR=1.10, 95%CI 0.86-1.42). Multivariate analysis among group B3 patients using Cox proportional hazard model revealed serum AFP value > 50 ng/mL was the only independent prognostic factor (HR = 1.93, 95%CI 1.04-3.56). The 5-year overall survival of group B3 was 47.3% when serum AFP < 50, and 27.6% when serum AFP > 50 (P = 0.033). Conclusion: Among intermediate stage HCC, Group B1 and B2 showed fair prognosis. However, group B3 showed rather poor prognosis unless serum AFP was < 50 ng/mL.

Role of liver resection in treating intermediate and advanced stage adolescent and young adult hepatocellular carcinoma patients: A propensity-matching cohort study

BackgroundHepatocellular carcinoma (HCC) in adolescent and younger adult (AYA) patients is usually diagnosed at an advanced stage such that curative treatments are often not possible. The aimed of this study was to compare the outcome of attempted curative treatment, liver resection (LR) versus transarterial chemoembolization (TACE), in AYA patients presenting with intermediate or advanced HCC defined by the Barcelona Clinic Liver Cancer (BCLC) stage B and C. MethodsAll AYA patients diagnosed with BCLC stage B or C HCC undertaking LR (n = 276) and TACE (n = 136) were included in our study. The prognostic factors of the patients were analyzed and the propensity score-matched patients (120 pairs) were analyzed to adjust for any baseline differences. ResultsThe overall survival rate of the patients undertaking LR was higher than TACE for the both entire and the propensity matched population (p < 0.001). In the multivariate analysis, propensity scoring analyses suggested that HBsAg positivity, macrovascular invasion, tumor size and TACE treatment were the independent prognostic factors associated with a worse survival outcome. ConclusionThe effect of LR was superior to that of TACE for patients with intermediate and advanced stage HCC. The survival outcome was associated with the tumor size, macrovascular invasion, and hepatitis history in AYA HCC patients.