Locoregional Therapy For Hepatocellular Carcinoma Research Articles

Histological Changes in Hepatocellular Carcinoma Post-locoregional Therapy

Locoregional therapies are widely practiced in treatment of primary hepatocellular carcinoma and metastatic carcinoma to the liver as they provide a more targeted treatment with lesser side effects. Transarterial chemo-embolisation and selective internal radiotherapy (SIRT) are a few examples. However, histopathological findings after locoregional therapy of hepatocellular carcinoma are rarely reported. We reported a case of a 61-year-old man with underlying Hepatitis B and subsequent hepatocellular carcinoma who was treated with SIRT followed by wedge liver resection. Macroscopically, the specimen showed a well-defined mass with areas of fibrosis and haemorrhage. Microscopic examination showed 70% tumour necrosis with numerous microspheres surrounded by multinucleated giant cells with histiocytes and chronic inflammatory cells. Currently, the patient is well with regular follow-up. The latest ultrasound findings showed no residual liver lesion in the background of liver cirrhosis. Although assessment of treatment response following locoregional therapy based on histopathological findings are not widely practiced, recognising histopathological changes such as tumour necrosis, provide valuable insight to a patient’s prognosis. Minimal to absent tumour necrosis implies poor response, limiting further locoregional therapy option. Findings of numerous microspheres might pose a diagnostic challenge as they mimic fungal organisms. Hence, histological examination with aid of special stains like periodic acid Schiff (PAS) and Grocott’s methenamine silver stain may be useful.

Locoregional therapies for hepatocellular carcinoma: Thecurrent status and future perspectives.

Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of cancer-related mortality. Locoregional therapies (LRTs) play a crucial role in HCC management and are selectively adopted in real-world practice across various stages. Choosing the best form of LRTs depends on technical aspects, patient clinical status and tumour characteristics. Previous studies have consistently highlighted the efficacy of combining LRTs with molecular targeted agents in HCC treatment. Recent studies propose that integrating LRTs with immune checkpoint inhibitors and molecular targeted agents could provide substantial therapeutic benefits, a notion underpinned by both basic and clinical evidence. This review summarised the current landscape of LRTs in HCC and discussed the anticipated outcomes of combinations with immunotherapy regimens.

New insights into mechanisms and interventions of locoregional therapies for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is responsible for a significant number of cancer-related deaths worldwide and its incidence is increasing. Locoregional treatments, which are precision procedures guided by imaging to specifically target liver tumors, play a critical role in the management of a substantial portion of HCC cases. These therapies have become an essential element of the HCC treatment landscape, with transarterial chemoembolization (TACE) being the treatment of choice for patients with intermediate to advanced stages of the disease. Other locoregional therapies, like radiofrequency ablation, are highly effective for small, early-stage HCC. Nevertheless, the advent of targeted immunotherapy has challenged these established treatments. Tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) have shown remarkable efficacy in clinical settings. However, their specific uses and the development of resistance in subsequent treatments have led clinicians to reevaluate the future direction of HCC therapy. This review concentrates on the distinct features of both systemic and novel locoregional therapies. We investigate their effects on the tumor microenvironment at the molecular level and discuss how targeted immunotherapy can be effectively integrated with locoregional therapies. We also examine research findings from retrospective studies and randomized controlled trials on various combined treatment regimens, assessing their validity to determine the future evolution of locoregional therapies within the framework of personalized, comprehensive treatment.

Erratum: Differential expression of hepatic cancer stemness and hypoxia markers in residual cancer after locoregional therapies for hepatocellular carcinoma.

Erratum: Differential expression of hepatic cancer stemness and hypoxia markers in residual cancer after locoregional therapies for hepatocellular carcinoma.

Locoregional Therapies for Hepatocellular Carcinoma prior to Liver Transplant: Comparative Pathologic Necrosis, Radiologic Response, and Recurrence

PurposeTo compare pathologic tumor necrosis rates after locoregional therapies (LRTs) for hepatocellular carcinoma (HCC) prior to liver transplantation and evaluate radiologic-pathologic correlation along with posttransplant HCC recurrence. Materials and MethodsConsecutive patients with solitary HCC bridged or downstaged with LRT from 2010 to 2022 were included. LRTs were transarterial chemoembolization (TACE), radioembolization (yttrium-90 [90Y]), ablation, and stereotactic body radiotherapy (SBRT). Upfront combination therapy options were TACE/ablation and TACE/SBRT. Subsequent therapy crossover due to local recurrence was allowed. Posttreatment imaging closest to the time of transplant, explant histopathologic necrosis, and tumor recurrence after transplant were reviewed. ResultsSeventy-three patients met inclusion criteria, of whom 5 (7%) required downstaging. 90Y alone (n = 36) and multimodal therapy (pooled upfront combination and crossover therapy, n = 23) resulted in significantly greater pathologic necrosis compared with TACE alone (n = 14; P = .01). High dose 90Y radiation segmentectomy (≥190 Gy; n = 27) and TACE/ablation (n = 7) showed highest rates of complete pathologic necrosis (CPN)—63% (n = 17) and 71% (n = 5), respectively. Patients with CPN had a mean lesion size of 2.5 cm, compared with 3.2 cm without CPN (P = .04), irrespective of LRT modality. HCC recurrence was more common in patients without CPN (16%, 6/37) than in those with CPN (3%, 1/36; P = .11). Using Liver Imaging Reporting and Data System (LI-RADS), a nonviable imaging response was 75% sensitive and 57% specific for CPN. ConclusionsRadiation segmentectomy and multimodal therapy significantly improved CPN rates compared with TACE alone. A LI-RADS treatment response of nonviable did not confidently predict CPN.

Combination Therapy of Immune Checkpoint Inhibitors with Locoregional Therapy for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is estimated to be the fourth leading cause of cancer-related deaths globally, and its overall prognosis is dismal because most cases are diagnosed at a late stage and are unamenable to curative treatment. The emergence of immune checkpoint inhibitors (ICIs) has dramatically improved the therapeutic efficacy for advanced hepatocellular carcinoma; however, their response rates remain unsatisfactory, partly because >50% of HCC exhibit an ICI-nonresponsive tumor microenvironment characterized by a paucity of cytotoxic T cells (immune-cold), as well as difficulty in their infiltration into tumor sites (immune excluded). To overcome this limitation, combination therapies with locoregional therapies, including ablation, transarterial embolization, and radiotherapy, which are usually used for early stage HCCs, have been actively explored to enhance ICI efficacy by promoting the release of tumor-associated antigens and cytokines, and eventually accelerating the so-called cancer-immunity cycle. Various combination therapies have been investigated in early- to late-phase clinical trials, and some have shown promising results. This comprehensive article provides an overview of the immune landscape for HCC to understand ICI efficacy and its limitations and, subsequently, reviews the status of combinatorial therapies of ICIs with locoregional therapy for HCC.

Repeated loco-regional therapies for hepatocellular carcinoma is associated with inferior outcome after living donor liver transplantation in cirrhotic patients: Erratum.

Repeated loco-regional therapies for hepatocellular carcinoma is associated with inferior outcome after living donor liver transplantation in cirrhotic patients: Erratum.

S3877 Hepatic Abscess Development Following Locoregional Therapy for Hepatocellular Carcinoma in Patients With Decompensated Cirrhosis & Prior Biliary Manipulation: A Case Series

S3877 Hepatic Abscess Development Following Locoregional Therapy for Hepatocellular Carcinoma in Patients With Decompensated Cirrhosis & Prior Biliary Manipulation: A Case Series

Role of Stereotactic Body Radiation Therapy in Portal Vein Tumor Thrombosis in Hepatocellular Carcinoma: A Prospective Single Institute Experience

Patients diagnosed with Hepatocellular carcinoma (HCC) complicated with portal vein tumor thrombosis (PVTT) have a limited number of treatment options available and are associated with an overall poor prognosis. With the recent developments in the field of radiation therapy, the role of radiotherapy particularly Stereotactic Body radiotherapy (SBRT) has increased as a loco-regional therapy for HCC. This study was planned to evaluate the role of SBRT in Locally advanced HCC complicated with PVTT and its role as loco-regional therapy. We conducted a prospective study that included patients diagnosed with HCC complicated with PVTT Child-Turcotte Pugh (CTP) Class A/B with a maximum score of 7, diagnosed on triple phase Contrast-Enhanced - MRI unsuitable for other ablative procedures. Patients with Bilirubin levels > 4 mg/dl, active Hepatitis, CTP score >7, normal liver volume <700cc or history of prior radiotherapy were excluded from the study. Patients underwent a contrast enhanced 4D-CT simulation with abdominal compression and were planned for SBRT using VMAT technique. Patients were followed-up as per Institute protocol. CECT or MRI for a radiological response was done for response assessment using mRECIST criteria version 1.1. A baseline MRI was done at one-month post-SBRT to understand any RT changes in the liver and to differentiate from tumor progression during the response assessment at three months. A total of 22 patients with HCC were recruited and received SBRT to PVTT, with a dosage between 30-42 Gy over 6 fractions treated on alternate days. Patients were assessed post-treatment with triphasic CE-MRI every 3 months as per institute protocol. Five patients had achieved Complete response in form of Portal vein recanalization. Three patients had Partial response to the treatment. Seven patients maintained stable disease status whereas six patients had disease progression during the entire course of treatment. The response rate (CR+PR) to treatment was 36.3% at the time of analysis. The Overall Response rate (CR+PR+SD) was 69%. No grade 3 or 4 toxicities were observed and treatment was tolerated well by patients. Kaplan-Meier method was applied to calculate the survival probability at various follow-up intervals. The median time for overall survival was 25 months ((95% CI: 15-35). Out of the 22 subjects included in the study, 6 patients died. There was a 78% survival probability at 12 months and a 68% survival probability at 18 months of follow-up. This prospective single-arm study demonstrated the vital role of SBRT in the treatment of Hepatocellular carcinoma with Portal vein tumor thrombosis and its efficacy in terms of achieving excellent local control with relatively lesser toxicities compared with existing treatment modalities. Patients have shown benefit post-treatment in terms of thrombus reduction and restoration of Portal vein flow making them suitable for further treatment like Resection or TACE.

Cancer Immunology: Impact of Radioembolization of Hepatocellular Carcinoma on Immune Response Modulation.

Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer and the fourth most common cause of cancer mortality. The tumor microenvironment is increasingly recognized as having a central role in HCC carcinogenesis; factors such as tumor and immune cell interactions, cytokines, and extracellular matrix have key roles. Transarterial radioembolization (TARE) is a locoregional therapy for HCC that not only has a direct tumoricidal effect but also induces an immune response against tumor cells with subsequent immunogenic cell death. This TARE-induced tumor immunogenicity occurs through enhancement of tumor-associated antigen expression and recruitment and diversification of tumor-infiltrating lymphocytes. In addition, immunologic biomarkers, including neutrophil-to-lymphocyte ratio, lymphocyte count, and cytokine levels, may be useful for predicting outcomes after TARE. Early data are promising regarding the potential synergistic benefit of treatment algorithms that combine TARE and immunotherapies, and interest is growing in the clinical application of such combinations. The purpose of this article is to provide an overview of cancer immunology, summarize the available data on the biologic effects of TARE on local and systemic immune responses, and explore the potential role of the combination of TARE and immunotherapy for HCC.

Abstract 5465: Immune cell dynamics of patients and mice with hepatocellular carcinoma treated with anti-PD-L1 plus anti-CTLA-4 combination therapy

Abstract Background: Hepatocellular carcinoma (HCC) is one of the major causes for cancer-related death. Single agent immunotherapy or combined immunotherapy have become the standard of care in advanced HCC. Recently, the combination of durvalumab (dur) plus a single dose of 300 mg tremelimumab (trem) (STRIDE regimen) have received FDA approval based on results from the HIMALAYA trial. However, immune responses have not been studied in detail. We tested the combination of 4 × 75 mg trem plus dur and locoregional therapies in HCC at and conducted correlative studies. Methods: We enrolled 28 patients with biopsy proven advanced HCC in an open-labeled phase 2 trial using dur and trem combined with ablative therapies (NCT02821754). Patients received four doses of 75mg trem every 4 weeks and 1500mg dur every 4 weeks until progression. Patients underwent an interventional radiologic procedure (RFA/TACE) on day 36. Peripheral blood mononuclear cells (PBMC) and serum from patients enrolled were collected at baseline and after 1 cycle (day 28). PBMC was analyzed by multicolor spectral cytometry using a 17 antibody pan immune cell panel and a 25 antibody T cell panel. Serum samples from patients were collected at baseline and on day 28. Serum samples were analyzed with a 34-plex cytokine/chemokine array. Mice with orthotopically injected HCC (RIL-175 and Hep55.1C) were treated with anti-PD-L1 plus anti-CTLA4 and followed for tumor responses. Hepatic lymphocytes, tumor infiltrating lymphocytes (TILs), and splenocytes were analyzed by spectral cytometry from mice treated with immune checkpoint inhibitors. Results: 28 patients with advanced HCC were enrolled in this study. The best clinical response for treatment was the following, partial response (PR, n=5), stable disease (SD, n=12), progressive disease (PD, n=8), and not evaluable (n=3). Median PFS and OS were 4.5 and 20.8 months respectively. Patient PBMC analysis demonstrated an increase of regulatory T cells 1.65 times from baseline after 28 days in all patients. The frequency of Tbet+CD4+ T cells showed a non-significant increase in patients demonstrating a PR. Serum cytokine analysis revealed the levels of IL-18, IL-10, CCL-2, and VEGF-a increased in responders after treatment. in contrast, an increase of IL-6 and TNF-alpha after treatment was found only in patients with PD. In animal experiments, the size of liver tumors treated with anti-PDL1 and anti-CTLA4 were significantly smaller than that with isotype controls. The lymphocytes in the adjacent livers and tumor-infiltrating lymphocytes (TILs) were analyzed. PD1+CD8+ T cells and Tbet+CD4+ T cells in the liver and TILs increased with combination treatment. Conclusion: Anti-PD-L1 and anti-CTLA4 combination therapy have an anti-tumor effect on HCC. We observed an expansion of PD1+ CD8+ T cells and Tbet+ CD4+ T cells. Citation Format: Yuta Myojin, Benjamin Ruf, Mohamed-Reda Benmebarek, Kylynda Bauer, Rajiv Trehan, Kelley Coffman, Chi Ma, Cecilia B. Monge, Changqing Xie, Tim Greten. Immune cell dynamics of patients and mice with hepatocellular carcinoma treated with anti-PD-L1 plus anti-CTLA-4 combination therapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5465.

Evaluating treatment response following locoregional therapy for hepatocellular carcinoma: A review of the available serological and radiological tools for assessment

Hepatocellular carcinoma (HCC) is an aggressive primary malignancy of the liver and is the third most common cause of cancer-related global mortality. There has been a steady increase in treatment options for HCC in recent years, including innovations in both curative and non-curative therapies. These advances have brought new challenges and necessary improvements in strategies of disease monitoring, to allow early detection of HCC recurrence. Current serological and radiological strategies for post-treatment monitoring and prognostication and their limitations will be discussed and evaluated in this review.

Image-guided percutaneous locoregional therapies for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the 3rd leading cause of cancer death worldwide. Treatment options include surgical resection, liver transplantation, imageguided percutaneous locoregional options, external beam radiation therapy (EBRT) and systemic therapies. Treatment choice depends on the stage of the disease and patient's characteristics including performance status and liver function. Barcelona Clinic Liver Cancer (BCLC) staging system, with its recent 2022 update, is one of the most widely endorsed staging system. Locoregional therapies (LRT) are recommended for very early stage (BCLC-0), early stage (BCLC-A), and the two first subgroups of intermediate stage (BCLC-B). Image-guided percutaneous locoregional therapies include ablation, mainly thermal ablation with radiofrequency (RFA), microwave ablations (MWA) and cryoablation, transarterial embolization (TAE, also known as bland embolization), transarterial chemoembolization (TACE), drug-eluding beadstransarterial chemoembolization (DEB-TACE), combination of ablation with embolization, transarterial radioembolization (TARE) also known as selective internal radioembolization therapy, and hepatic artery infusion (HAI). While ablation is recognized as a curative therapy, all intra-arterial therapies are considered non-curative options. There is growing evidence that TARE, through radiation segmentectomy, can be considered a curative intent treatment in appropriate selective patients. In this article, we will review indications, complications, and outcomes of locoregional therapies for HCC.

The locoregional therapy for hepatocellular carcinoma

The locoregional therapy for hepatocellular carcinoma

Differential expression of hepatic cancer stemness and hypoxia markers in residual cancer after locoregional therapies for hepatocellular carcinoma.

Transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) treatment to hepatocellular carcinoma (HCC) are effective tools to control tumor growth, prolong survival, palliate symptoms, and improve quality of life for patients with intermediate‐stage HCC. Nevertheless, there is high variability of local HCC responses to locoregional therapies; therefore, better and personalized prediction of tumor response to TACE is necessary for management of patients with HCC, especially when these modalities of treatment are used to bridge patients for liver transplant. Here, we investigated differential expression of hepatic cancer stem cell and hypoxia in residual HCC after TACE treatment in comparison with TARE. A publicly available gene data set was screened for differentially expressed genes (DEGs) in TACE_Response compared with TACE_Non‐response HCC. Analysis of the GSE104580 data set displayed a total of 406 DEGs, including 196 down‐regulated and 210 up‐regulated DEGs. Of the 196 down‐regulated DEGs, three hepatic cancer stem cell (CSC) markers and 11 hypoxia‐related genes were identified. Immunohistochemical staining of hepatic CSC and hypoxia markers on explant liver tissues exhibited more intense positive staining of hepatic CSC markers (CD24, EpCAM) and hypoxia marker carbonic anhydrase 9 (CA9) in residual tumor nodule from patients with HCC treated with TACE compared with nontreated patients. Furthermore, Pearson's correlation analysis revealed the significant correlation between hepatic CSC markers and hypoxia marker, CA9. Conclusion: Hepatic CSC and hypoxia markers predict nonresponse to TACE and are differentially expressed in residual tumor after TACE compared with TARE. In the long term, TACE‐induced hypoxia may select an aggressive HCC phenotype.

Abstract CT546: A phase 2, multicenter study to evaluate the efficacy and safety of TACE sequential tislelizumab as adjuvant therapy in patients with HCC at high risk of recurrence after curative resection

Abstract Background: Surgical resection is one of the most important radical treatment in hepatocellular carcinoma (HCC). However, the 5-year recurrence rate of HCC after surgery is up to 70%, hampering further improvement in the prognosis of HCC patients. Risk factors for recurrence include microvascular invasion (MVI), multiple lesion and solitary tumor ≥ 5 cm, etc. Postoperative adjuvant treatment with transarterial chemoembolization (TACE) can reduce the recurrence rate and improve overall survival (OS) for patients with high risk of recurrence to some extent. TACE treatment promotes the release of tumor related antigen and the recruitment of immune cells by killing tumor cells, thereby promoting the anti-tumor immune response; it may have a potential synergistic effect with PD-1 blockade. Currently, there is no ongoing study on TACE combined with immunotherapy as postoperative adjuvant therapy for HCC. This is an open-label, multicenter, phase II study to evaluate the efficacy and safety of TACE sequential tislelizumab as adjuvant therapy in HCC patients with high risk of recurrence after curative resection (NCT04981665). Trial design: Eligible patients are ≥18 y, ECOG PS 0 or 1, Child-Pugh class A, diagnosed with HCC confirmed by histopathology or cytology, with no prior systematic treatment and locoregional therapy for HCC, and have received a curative resection with high risk of recurrence fulfilling one of the following criteria: (1) a solitary tumor &amp;gt; 5 cm, (2) solitary tumor &amp;gt; 2 cm and ≤ 5 cm with MVI, (3) 2-3 lesions. 50 pts will receive TACE treatment once (4±1 w) after curative resection, then followed by tislelizumab 200 mg IV Q3W (5±2 d). Tislelizumab will be administered until disease recurrence, intolerable toxicity, death, withdrawal of consent or completion of a maximum of 17 cycles of tislelizumab. Primary endpoint is 2-year recurrence-free survival rate (2-year RFS rate). Secondary endpoints include RFS, time to recurrence, OS, 1-year RFS rate, 1-year and 2-year OS rate, and safety. Exploratory endpoints include biomarkers related to the response and prognosis of adjuvant TACE sequential tislelizumab therapy. Citation Format: Tingbo Liang, Zongli Zhang, Jinfang Zheng, Yijun Wang, Jialin Zhang, Bo Li, Tao Ma, Yunfei Xu, Changxiong Wu, Quan Sun, Yiman Meng, Xiaoli Yang. A phase 2, multicenter study to evaluate the efficacy and safety of TACE sequential tislelizumab as adjuvant therapy in patients with HCC at high risk of recurrence after curative resection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT546.

Optimization of the BCLC Staging System for Locoregional Therapy for Hepatocellular Carcinoma by Using Quantitative Tumor Burden Imaging Biomarkers at MRI.

Background Patients with intermediate- and advanced-stage hepatocellular carcinoma (HCC) represent a highly heterogeneous patient collective with substantial differences in overall survival. Purpose To evaluate enhancing tumor volume (ETV) and enhancing tumor burden (ETB) as new criteria within the Barcelona Clinic Liver Cancer (BCLC) staging system for optimized allocation of patients with intermediate- and advanced-stage HCC to undergo transarterial chemoembolization (TACE). Materials and Methods In this retrospective study, 682 patients with HCC who underwent conventional TACE or TACE with drug-eluting beads from January 2000 to December 2014 were evaluated. Quantitative three-dimensional analysis of contrast-enhanced MRI was performed to determine thresholds of ETV and ETB (ratio of ETV to normal liver volume). Patients with ETV below 65 cm3 or ETB below 4% were reassigned to BCLC Bn, whereas patients with ETV or ETB above the determined cutoffs were restratified or remained in BCLC Cn by means of stepwise verification of the median overall survival (mOS). Results This study included 494 patients (median age, 62 years [IQR, 56-71 years]; 401 men). Originally, 123 patients were classified as BCLC B with mOS of 24.3 months (95% CI: 21.4, 32.9) and 371 patients as BCLC C with mOS of 11.9 months (95% CI: 10.5, 14.8). The mOS of all included patients (including the BCLC B and C groups) was 15 months (95% CI: 12.3, 17.2). A total of 152 patients with BCLC C tumors were restratified into a new BCLC Bn class, in which the mOS was then 25.1 months (95% CI: 21.8, 29.7; P < .001). The mOS of the remaining patients (ie, BCLC Cn group) (n = 222; ETV ≥65 cm3 or ETB ≥4%) was 8.4 months (95% CI: 6.1, 11.2). Conclusion Substratification of patients with intermediate- and advanced-stage hepatocellular carcinoma according to three-dimensional quantitative tumor burden identified patients with a survival benefit from transarterial chemoembolization before therapy. © RSNA, 2022 Online supplemental material is available for this article.

Repeated loco-regional therapies for hepatocellular carcinoma is associated with inferior outcome after living donor liver transplantation in cirrhotic patients.

Liver transplantation is the definitive treatment for defined stage hepatocellular carcinoma (HCC) in cirrhotic patients. Loco-regional therapy (LRT) may be considered before transplantation to prevent the disease progression and the patient from dropping out of the waiting list. This study aims to evaluate the impact of repeated pretransplant LRTs on the long-term outcomes in HCC liver transplant recipients. Between 2004 and 2019, living donor liver transplantation (LDLT) recipients with viable HCC on the explant livers were enrolled. Uni- and multivariate analysis was performed with the Cox regression model to stratify the risk factors associated with HCC recurrence and patent survival after LDLT. A total of 124 patients were enrolled, in which 65.3% (n = 81) were Barcelona Clinic Liver Cancer classification stage B or D and 89% (n = 110) had advanced fibrosis or cirrhosis on the explanted livers. After a median follow-up of 41 months (IQR: 24-86.5), there were 18 cases (13.7%) of HCC recurrence. Univariate analysis showed that the model of end-stage liver disease and Child-Turcotte-Pugh score, pretransplant alpha-fetoprotein value (>500 ng/ml), repeated pretransplant LRTs (N > 4), increased tumor numbers and maximal size, presence of microvascular invasion, and the histological grading of the tumors are risk factors of inferior outcomes. In multivariate analysis, only repeated pretransplant LRTs (N > 4) had a significant impact on both the overall- and recurrence-free survival. The impact of pretransplant LRT was consistently significant among subgroups based on their LRT episodes (N = 0, 1-4, >4 respectively). Repeated LRT for HCC can be associated with the risk of tumor recurrence and inferior patient survival after LDLT in cirrhotic patients. Early referral of those eligible for transplantation may improve the treatment outcomes in these patients.

Multiple Light-Activated Photodynamic Therapy of Tetraphenylethylene Derivative with AIE Characteristics for Hepatocellular Carcinoma via Dual-Organelles Targeting.

Photodynamic therapy (PDT) has emerged as a promising locoregional therapy of hepatocellular carcinoma (HCC). The utilization of luminogens with aggregation-induced emission (AIE) characteristics provides a new opportunity to design functional photosensitizers (PS). PSs targeting the critical organelles that are susceptible to reactive oxygen species damage is a promising strategy to enhance the effectiveness of PDT. In this paper, a new PS, 1-[2-hydroxyethyl]-4-[4-(1,2,2-triphenylvinyl)styryl]pyridinium bromide (TPE-Py-OH) of tetraphenylethylene derivative with AIE feature was designed and synthesized for PDT. The TPE-Py-OH can not only simultaneously target lipid droplets and mitochondria, but also stay in cells for a long period (more than 7 days). Taking advantage of the long retention ability of TPE-Py-OH in tumor, the PDT effect of TPE-Py-OH can be activated through multiple irradiations after one injection, which provides a specific multiple light-activated PDT effect. We believe that this AIE-active PS will be promising for the tracking and photodynamic ablation of HCC with sustained effectiveness.

Hepatocellular carcinoma locoregional therapies: Outcomes and future horizons.

Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver and has an overall five-year survival rate of less than twenty percent. For patients with unresectable disease, evolving liver-directed locoregional therapies provide efficacious treatment across the spectrum of disease stages and via a variety of catheter-directed and percutaneous techniques. Goals of locoregional therapies in HCC may include curative intent in early-stage disease, bridging or downstaging to surgical resection or transplantation for early or intermediate-stage disease, and local disease control and palliation in advanced-stage disease. This review explores the outcomes of chemoembolization, bland embolization, radioembolization, and percutaneous ablative therapies. Attention is also given to prognostic factors related to each of the respective techniques, as well as future directions of locoregional therapies for HCC.