Locoregional Treatment For Hepatocellular Carcinoma Research Articles

Clinical Results of Holmium-166 Radioembolization with Personalized Dosimetry for the Treatment of Hepatocellular Carcinoma

Transarterial radioembolization (TARE) with 166Ho-loaded microspheres is an established locoregional treatment for hepatocellular carcinoma (HCC), introduced in 2010. This study evaluates the clinical outcome of patients with HCC who underwent 166Ho-TARE with personalized dosimetry. Twenty-seven patients with 36 TARE procedures were analyzed. Treatment planning, execution, and evaluation was possible without complications in all cases. At the 3-month follow-up, disease control in the treated liver was achieved in 81.8% of patients (complete remission, partial remission, and stable disease in 36.4%, 31.8%, and 13.6%, respectively). The median overall survival (OS) was 17.2 months, and progression-free survival (PFS) in the treated liver was 11 months. Statistically significant positive correlations were observed between the achieved radiation dose for the tumor and both PFS (r = 0.62, p < 0.05) and OS (r = 0.48, p < 0.05), suggesting a direct dose–response relationship. The calculated achieved dose was 8.25 Gy lower than the planned dose, with relevant variance between planned and achieved doses in individual cases. These results confirm the efficacy of the 166Ho-TARE holmium platform and underscore the potential of voxel-based, personalized dosimetry to improve clinical outcomes.

Integrating Navigation-Assisted Ablation in the Locoregional Treatment of Hepatocellular Carcinoma

With the increasing prevalence of hepatocellular carcinoma (HCC), ablative therapy is a critical treatment option to achieve a cancer-free state. The anatomic location of the tumor can be a challenge, and select hepatic locations of a tumor require laparoscopic-assisted strategies to safely reach and treat the lesion. To assess the association of real-time ultrasonography-augmented navigation for HCC ablation with patient survival, operative time, and rate of incomplete ablations. This retrospective case-control study was conducted among a prospectively collected database of more than 750 patients with HCC who were treated with ablation therapy with and without the use of navigation at a single quaternary medical center from June 2011 to January 2021. Data were analyzed from October 2022 through June 2023. Real-time ultrasonography-augmented navigation. The primary outcome was rate of incomplete ablations in patients undergoing HCC ablation with vs without navigation. Secondary outcomes included overall survival (OS), progression-free survival (PFS), and operative time. The analytic cohort included 467 patients (mean [SD] age, 62.4 [7.8] years; 355 male [76.0%]; 21 Hispanic [4.5%], 67 non-Hispanic Black [14.5%], and 347 Non-Hispanic White [75.0%] among 463 patients with race and ethnicity data). The most common etiology of liver disease was hepatitis C infection (187 patients with etiology data [40.0%]), and 348 of 458 patients with TMN staging data (76.0%) had TNM stage 1 disease. There were 187 individuals treated with navigation and 280 individuals treated without navigation. Patients who underwent navigation-assisted ablation were more likely to have stage 2 disease based on TNM staging (62 of 183 patients [33.9%] vs 47 of 275 patients [17.1%] with TMN data; P < .002) and had a higher mean (SD) number of lesions (1.3 [0.5] vs 1.2 [0.5] lesions; P = .002) and a longer mean (SD) operation time (113.2 [29.4] vs 109.6 [32.3] minutes; P = .04). Patients who underwent navigation were also more likely to have tumors in segment 8 (59 patients [32.1%] vs 53 of 275 patients with segment data [19.3%] with segment data; P = .005) and less likely to have tumors in segment 4 (20 patients [10.9%] vs 54 patients with segment data [19.6%]; P = .005). Overall mean (SD) time to recurrence after treatment was 10.0 (12.5) months, with similar rates for patients with navigation vs no navigation. There were no differences in incomplete ablation rate (10 patients [9.2%] vs 10 patients [10.5%]; P = .32), OS, or PFS between patients undergoing ablation with and without navigation. In this study, use of navigation was associated with comparable outcomes to undergoing ablation without navigation, although patients with navigation had more locally advanced disease. These findings suggest that use of real-time navigation in laparoscopic-assisted ablation of liver cancer should be considered as a useful tool for treating challenging tumors.

Neoadjuvant and Adjuvant Systemic Therapies in Loco-Regional Treatments for Hepatocellular Carcinoma: Are We at the Dawn of a New Era?

Despite maximizing techniques and patient selection, liver resection and ablation for HCC are still associated with high rates of recurrence. To date, HCC is the only cancer with no proven adjuvant or neoadjuvant therapy used in association to potentially curative treatment. Perioperative combination treatments are urgently needed to reduce recurrence rates and improve overall survival. Immunotherapy has demonstrated encouraging results in the setting of adjuvant and neoadjuvant treatments for non-hepatic malignancies. Conclusive data are not yet available in the context of liver neoplasms. However, growing evidence suggests that immunotherapy, and in particular immune checkpoint inhibitors, could represent the cornerstone of an epochal change in the treatment of HCC, improving recurrence rates and overall survival through combination treatments. Furthermore, the identification of predictive biomarkers of treatment response could drive the management of HCC into the era of a precision medicine. The purpose of this review is to analyze the state of the art in the setting of adjuvant and neoadjuvant therapies for HCC in association with loco-regional treatments in patients not eligible for liver transplantation and to hypothesize future scenarios.

The Role of Branched-Chain Amino Acid Supplementation in Combination with Locoregional Treatments for Hepatocellular Carcinoma: Systematic Review and Meta-Analysis.

Branched-chain amino acid (BCAA) supplementation has been linked with favorable outcomes in patients undergoing surgical or palliative treatments for hepatocellular carcinoma (HCC). To date, there has been no systematic review investigating the value of BCAA supplementation in HCC patients undergoing locoregional therapies. A systematic search of the literature was performed across five databases/registries using a detailed search algorithm according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. The search was conducted on March 23, 2022. Sixteen studies with a total of 1594 patients were analyzed. Most patients were male (64.6%) with a mean age of 68.2 ± 4.1 years, Child-Pugh score A (67.9%) and stage II disease (40.0%). Locoregional therapy consisted of radiofrequency ablation, transarterial chemoembolization or hepatic artery infusion chemotherapy. BCAA supplementation was in the form of BCAA granules or BCAA-enriched nutrient. Most studies reported improved albumin levels, non-protein respiratory quotient and quality of life in the BCAA group. Results pertaining to other outcomes including overall survival, recurrence rate, and Child-Pugh score were variable. Meta-analysis showed significantly higher levels of post-treatment serum albumin in the BCAA group (SMD = 0.54, 95% CI 0.20-0.87) but no significant differences in mortality rate (RR = 0.81, 95% CI: 0.65-1.02) and AST (SMD = -0.13, 95% CI: -0.43-0.18). BCAA supplementation is associated with higher post-treatment albumin levels. There are currently not sufficient data to support additional benefits. Further studies are needed to elucidate their value.

Proton Beam Therapy versus Radiofrequency Ablation for Patients with Treatment-Naïve Single Hepatocellular Carcinoma: A Propensity Score Analysis

Introduction: Proton beam therapy (PBT) is known to be an effective locoregional treatment for hepatocellular carcinoma (HCC). However, few comparative studies in treatment-naïve cases have been reported. The aim of this study was to compare the survival outcomes of PBT with those of radiofrequency ablation (RFA) in patients with treatment-naïve solitary HCC. Methods: Ninety-five consecutive patients with treatment-naïve HCC, a single nodule measuring ≤5 cm in diameter, and a Child-Pugh score of ≤8 who were treated with PBT at the University of Tsukuba Hospital between 2001 and 2013 were enrolled in the study. In addition, 836 patients with treatment-naïve HCC treated by RFA at the University of Tokyo Hospital during the same period were analyzed as controls. Recurrence-free survival (RFS) and overall survival (OS) were compared in 83 patient pairs after propensity score matching. Results: The 1-year, 3-year, and 5-year RFS rates were 86.6%, 49.5%, and 35.5%, respectively, in the PBT group and 59.5%, 34.0%, and 20.9% in the RFA group (p = 0.058); the respective OS rates were 97.6%, 77.8%, and 57.1% in the PBT group and 95.1%, 81.7%, and 67.7% in the RFA group (p = 0.16). Regarding adverse effects, no grade 3 or higher adverse events were noted in the PBT; however, two grade 3 adverse events occurred within 30 days of RFA in the RFA group: one hemoperitoneum and one hemothorax. Discussion: After propensity score matching, PBT showed no significant difference in RFS and OS compared to RFA. PBT can be an alternative for patients with solitary treatment-naïve HCC.

Expression Patterns of Tumor Markers in Liver Transplant Recipients Showing Complete Pathological Response of Hepatocellular Carcinoma.

Complete pathological response (CPR) is achieved with various pretransplant locoregional treatments for hepatocellular carcinoma (HCC). This study aimed to investigate pretransplant expression of HCC tumor markers in liver transplantation (LT) recipients showing CPR. For the CPR group, 166 patients were selected from a single-institution LT database. Two control groups of 332 patients without HCC and 184 patients with partial pathological response (PPR) were also selected. The model for end-stage liver disease score in the CPR group was 11.5 ± 7.7. The number of transcatheter arterial chemoembolization sessions before LT was one in 68 patients (14.0%), two in 38 patients (22.9%), and three or more in 60 patients (36.1%). A solitary non-viable tumor was identified in 120 (86.4%) of the explant livers and the largest tumor size was 2.4 ± 1.3 cm. Living-donor and deceased-donor LTs were performed in 152 (91.6%) and 14 (8.4%) patients, respectively. The median levels of α-fetoprotein (AFP) and protein induced by Vitamin K absence or antagonist-II (PIVKA-II) measured within two weeks before LT were 4.2 ng/mL and 20 mAU/mL, respectively. These tumor marker levels were comparable to those in the no-HCC control group, but much lower than those in the PPR group (p < 0.001). Receiver operating characteristic curve analysis of AFP and PIVKA-II showed no definite cutoff values for CPR in the cohort of CPR and no-HCC patients, but significant cutoffs of 6.5 ng/mL for AFP and 29 mAU/mL for PIVKA-II were obtained in the cohort of CPR and PPR patients. The 1-, 3- and 5-year HCC recurrence and overall patient survival rates of the CPR group were 5.1% and 93.3%, 7.6% and 89.6%, and 7.6% and 89.6%, respectively. These tumor recurrence rates were much lower than those in the PPR group (p < 0.001). In conclusion, the present study results suggest that normalizing AFP and PIVKA-II after locoregional treatment is indicative of CPR. However, some CPR patients showed high expression of tumor markers; thus, pretransplant values of HCC tumor markers should be interpreted with caution.

Impact and the delivery of loco-regional treatment for hepatocellular carcinoma during the COVID-19 pandemic

Hepatocellular carcinoma (HCC) is the second most lethal tumour, with therapies broadly divided into curative and palliative intent. Unfortunately, the majority of HCCs were found to be unresectable at diagnosis. Advances in novel loco-regional therapies have given patients with unresectable HCC a vital chance for disease control and survival. However, the COVID-19 pandemic has greatly shaped and impacted treatment protocols and delivery for HCC patients. This review article aims to describe the impact of the COVID-19 pandemic on the delivery of loco-regional treatment modalities for HCC and compare treatment trends between the pre -pandemic and pandemic eras. Treatment of HCC involves complex collaboration between clinical professionals within their local and global healthcare institutions. The COVID-19 pandemic has had a profound impact on the treatment of HCC. The delivery of loco-regional treatment for HCC will need to adapt to each healthcare system's unique structure.

S3546 Transcatheter Arterial Radioembolization (TARE)-Induced Gastric Ulcer in an Excluded Stomach After Roux-en-Y Gastric Bypass

Introduction: Transcatheter arterial radioembolization (TARE) is a commonly utilized locoregional treatment for hepatocellular carcinoma (HCC) and confers lower risk of hepatic ischemia owing to the safety profile of Yttrium-90 glass microspheres used in TARE. However, peptic ulcer disease occurs in 1-5% of TARE treatments. Here we describe a unique case of a TARE-induced gastric ulcer in an excluded stomach after Roux-en-Y gastric bypass (RYGB). Case Description/Methods: 70-year-old male with RYGB in 2012 and hepatitis C/nonalcoholic steatohepatitis cirrhosis complicated by HCC treated with TARE and liver transplant six months earlier was evaluated for melena. Esophagogastroduodenoscopy, colonoscopy, and an antegrade double balloon-assisted enteroscopy (DBE) found no obvious source. The excluded stomach could not be reached during DBE. Due to continued melena and transfusion dependence, he underwent a laparoscopic assisted gastroduodenoscopy (GD) to evaluate the excluded stomach. This revealed a 3 cm gastric ulcer in the pre-pylorus with biopsies showing radiation induced ulcer without evidence of malignancy, viral infection, or helicobacter pylori (Figure 1a). Gastrostomy tube (G-tube) access was maintained in the excluded stomach to administer twice daily liquid proton pump inhibitor (PPI) via the G-tube. Repeat GD after eight weeks of treatment showed a well-healing gastric ulcer (Figure 1b). Patient’s hemoglobin also stabilized and had no further transfusion requirement. Discussion: Gastric ulcers in the excluded stomach after RYGB are rare, especially 10 years after surgery. To our knowledge, this is the first reported incident of radiation induced ulcer in an excluded stomach. For treatment, G-tube access was maintained to the excluded stomach for administration of liquid PPI with excellent ulcer healing and resolution of melena and anemia. This treatment approach was selected based on previous data demonstrating benefit of open capsule PPI to treat marginal ulcers following RYGB1. Open capsule PPI administration is thought to enhance healing in these cases as this bypasses the need for capsular breakdown in the stomach for absorption, but it is unclear if a similar mechanism is true for an excluded stomach and warrants further studies to better understand its pharmacokinetics. This case highlights a unique case of a TARE-induced gastric ulcer in the RYGB excluded stomach that was successfully treated with liquid PPI.Figure 1.: (a) High power view of the ulcer slough shows fibrosis with prominent atypical fibroblasts consistent with radiation enteritis (H&E, 400×) (b) Repeat gastroduodenoscopy showing healing ulcer.

Combination approaches in hepatocellular carcinoma: How systemic treatment can benefit candidates to locoregional modalities.

The management of hepatocellular carcinoma (HCC) is challenging because most patients have underlying cirrhosis, and the treatment provides, historically, a limited impact on the natural history of patients with advanced-stage disease. Additionally, recurrence rates are high for those patients who receive local and locoregional modalities, such as surgical (resection and transplantation) or image-guided (ablation and intra-arterial) therapies. Translational research has led to new concepts that are reshaping the current clinical practice. Substantial advancements were achieved in the understanding of the hallmarks that drive hepatocarcinogenesis. This has primed a successful incorporation of novel agents with different targets, such as anti-angiogenic drugs, targeted-therapies, and immune-checkpoint inhibitors. Although clinical trials have proven efficacy of systemic agents in advanced stage disease, there is no conclusive evidence to support their use in combination with loco-regional therapy. While novel local modalities are being incorporated (e.g., radioembolization, microwave ablation, and irreversible electroporation), emerging data indicate that locoregional treatments may induce tumor microenvironment changes, such as hyperexpression of growth factors, release of tumor antigens, infiltration of cytotoxic lymphocytes, and modulation of adaptative and innate immune response. Past trials that evaluated the use of antiangiogenic drugs in the adjuvant setting after ablation or chemoembolization fail to demonstrate a substantial improvement. Current efforts are directed to investigate the role of immunotherapy-based regimens in this context. The present review aims to describe the current landscape of systemic and locoregional treatments for HCC, present evidence to support combination approaches, and address future perspectives.

Enhanced Tumoricidal Immune Responses by Transarterial Chemotherapy Using Novel Nanocomplexes in a Rat Liver Cancer Model.

Locoregional treatments for hepatocellular carcinoma (HCC) induce immunogenic cell death and a tumor-specific immune response, but infiltration and activation of immune cells in the liver have not been clearly described. Transarterial chemoembolization (TACE) or transarterial chemotherapy (TAC) without embolization have been used to treat intermediate or advanced stage HCC patients. The identification of intrahepatic immune cell changes after locoregional therapy provides a theoretical basis for the combination with immune checkpoint inhibitors (ICIs) in HCC. This study aimed to determine the anticancer effect and changes in the liver immune cell population and function after direct injection of polymerized phenylboronic acid-conjugated doxorubicin (pPBA-Dox) nanocomplexes into the liver through TAC. pPBA-Dox nanocomplexes were delivered directly to the liver cancer in a rat model by transarterial methods. Anticancer effect was confirmed by magnetic resonance imaging (MRI), and the immune cell population and functional changes were confirmed by flow cytometry (FACS). We first established a rat liver cancer model by implanting McA-RH7777 into rats and confirmed the formation of liver cancer through MRI, pathological examinations, and biochemical tests. Transarterial injection of pPBA-Dox nanocomplexes had a stronger anticancer effect than conventional Dox alone. Higher numbers of CD8+ and CD4+ T cells with activated phenotypes were infiltrated into the tumor microenvironment after transarterial pPBA-Dox treatments than after Dox alone treatment, suggesting the induction of stronger local immune responses by pPBA-Dox than Dox alone. This study provides a theoretical basis for TAC combined with ICIs and insight into novel targeted therapies using nanocomplexes for the treatment of HCC.

Gamma knife radiosurgery versus transcatheter arterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombus: a propensity score matching study

BackgroundThe optimal locoregional treatment for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) is unclear. This study aimed to investigate the efficacy of Gamma knife radiosurgery (GKR) versus transcatheter arterial chemoembolization (TACE) in HCC patients with PVTT.MethodsThis retrospective study included 544 HCC patients with PVTT (GKR, 202; TACE, 342). Propensity score matching (PSM) analysis identified 171 matched pairs of patients. The primary endpoint was overall survival (OS).ResultsBefore PSM, the GKR group exhibited longer median OS (mOS) than the TACE group (17.2 vs. 8.0 months, p < 0.001). We followed the Cheng’s classification for PVTT. In the subgroup analysis, GKR was associated with significantly longer mOS for patients with PVTT II-IV (17.5 vs. 8.7 months, p < 0.001; 17.2 vs. 7.8 months, p = 0.001; 14.5 vs. 6.5 months, p = 0.001, respectively) and comparable OS for patients with PVTT I. After PSM, the GKR group had also a longer mOS than the TACE group (15.8 vs. 10.4 months, p < 0.001). In the subgroup analysis, the GKR group demonstrated superior mOS for patients with PVTT II-IV (all p < 0.05) and comparable OS for patients with PVTT I.ConclusionsGKR was associated better OS than TACE in HCC patients with PVTT, especially for patients with PVTT II-IV.Clinical Trials RegistrationThe study was registered in the Chinese Clinical Trials Registry under the registration number ChiCTR2100051057.

MRI features of treated hepatocellular carcinoma following locoregional therapy: a pictorial review.

Hepatocellular carcinoma (HCC) is a leading cause of cancerdeath worldwide and within the United States. Liver transplant or partial liver resection is the definitive treatment of choice for HCC; however, the majority of cases are detected in advanced stages due to its early-stage asymptomatic nature, often precluding surgical treatment. Locoregional therapy plays an essential role in HCC management, including curative intent, as a bridge to transplant, or in some cases palliative therapy. Radiologists play a critical role in assessing tumor response following treatment to guide further management that may potentially impact transplantation eligibility; therefore, it is important for radiologists to have an understanding of different locoregional therapies and the variations of imaging response to different therapies. In this review article, we outline the imaging response to ablative therapy (AT), transarterial chemoembolization (TACE), selective internal radiation therapy (SIRT), and stereotactic body radiation therapy (SBRT). We will also briefly discuss the basic concepts of these locoregional therapies. This review focuses on the imaging features following locoregional treatment for hepatocellular carcinoma following AT, TACE, SIRT, and SBRT.

Loco-regional treatment of hepatocellular carcinoma: Role of contrast-enhanced ultrasonography.

Hepatocellular carcinoma (HCC) is one of the few cancers for which locoregional treatments (LRTs) are included in international guidelines and are considered as a valid alternative to conventional surgery. According to Barcelona Clinic Liver Cancer classification, percutaneous treatments such as percutaneous ethanol injection, radiofrequency ablation and microwave ablation are the therapy of choice among curative treatments in patients categorized as very early and early stage, while transcatheter arterial chemoembolization is considered the better option for intermediate stage HCC. A precise assessment of treatment efficacy and surveillance is essential to optimize survival rate, whereas residual tumor requires additional treatment. Imaging modalities play a key role in this task. Currently, contrast-enhanced computed tomography/magnetic resonance imaging are considered the standard imaging modalities for this purpose. Contrast enhanced ultrasound (CEUS), using second generation contrast agents, plays an increasingly important role in detecting residual disease after LRTs. CEUS is a straightforward to perform, repeatable and cost-effective imaging modality for patients with renal failure or iodine allergies. Due to the ability to focus on single regions, CEUS can also provide high temporal resolution. Moreover, several studies have reported the same or better diagnostic accuracy as contrast-enhanced computed tomography for assessing tumor vascularity 1 mo after LRTs, and recently three-dimensional (3D)-CEUS has been reported as a promising technique to improve the evaluation of tumor response to therapy. Furthermore, CEUS could be used early after procedures in monitoring HCC treatments, but nowadays this indication is still debated, and data from literature are conflicting, especially after transcatheter arterial chemoembolization procedure.

Loco-Regional Treatments for Hepatocellular Carcinoma in People Living with HIV.

Hepatocellular carcinoma (HCC) accounts for approximately 75–90% of primary liver cancers and is the sixth most common cancer and the third leading cause of cancer-related deaths worldwide. In the HIV-positive population, the risk of HCC is approximately four times higher than in the general population, with higher cancer-specific mortality than in HIV-negative patients. In most cases, HCC diagnosis is made in patients younger than the HIV-negative population and in the intermediate-advanced stage, thus limiting the therapeutic possibilities. Treatment choice in HIV-positive patients with HCC is subject to cancer staging, liver function and health status, as for HIV-negative and non-HIV-negative HCC patients. There are relatively few studies on the efficacy and safety in HIV-positive patients to date in loco-regional treatments for HCC. So far, literature shows that curative treatments such as radiofrequency ablation (RFA) have no significant differences in overall survival between HIV-positive and HIV-negative patients, as opposed to palliative treatments such as TACE, where there is a significant difference in overall survival. Although it can be assumed that the most recently discovered loco-regional therapies are applicable to HIV-positive patients with HCC in the same way as HIV-negative patients, further studies are needed to confirm this hypothesis. The purpose of our review is to evaluate these treatments, their efficacy, effectiveness, safety and their applicability to HIV-positive patients.

Molecular Imaging of Tumor Microenvironment to Assess the Effects of Locoregional Treatment for Hepatocellular Carcinoma.

Liver cancer is one of the leading causes of cancer deaths worldwide. Among all primary liver cancers, hepatocellular carcinoma (HCC) is the most common type, representing 75%‐85% of all primary liver cancer cases. Median survival following diagnosis of HCC is approximately 6 to 20 months due to late diagnosis in its course and few effective treatment options. Interventional therapy with minimal invasiveness is recognized as a promising treatment for HCC. However, due to the heterogeneity of HCC and the complexity of the tumor microenvironment, the long‐term efficacy of treatment for HCC remains a challenge in the clinic. Tumor microenvironment, including factors such as hypoxia, angiogenesis, low extracellular pH, interstitial fluid pressure, aerobic glycolysis, and various immune responses, has emerged as a key contributor to tumor residual and progression after locoregional treatment for HCC. New approaches to noninvasively assess the treatment response and assist in the clinical decision‐making process are therefore urgently needed. Molecular imaging tools enabling such an assessment may significantly advance clinical practice by allowing real‐time optimization of treatment protocols for the individual patient. This review discusses recent advances in the application of molecular imaging technologies for noninvasively assessing changes occurring in the microenvironment of HCC after locoregional treatment.

Incorporation of Ancillary MRI Features Into the LI-RADS Treatment Response Algorithm: Impact on Diagnostic Performance After Locoregional Treatment of Hepatocellular Carcinoma.

BACKGROUND. The LI-RADS treatment response algorithm may lack sufficient sensitivity for viable tumor after locoregional treatment (LRT) for hepatocellular carcinoma (HCC). OBJECTIVE. The purpose of our study was to evaluate the impact of incorporation of ancillary MRI features on the diagnostic performance of the LI-RADS treatment response algorithm after LRT for HCC. METHODS. This retrospective study included 141 patients (114 men, 27 women; median age, 56 years) who underwent gadoxetic acid-enhanced MRI after LRT for HCC between October 2005 and January 2020 and subsequent liver surgery. Two readers assessed lesions for LI-RADS features of viability for ancillary MRI features (transitional phase [TP] hypointensity, hepatobiliary phase [HBP] hypointensity, DWI hyperintensity or low ADC, and mild-to-moderate T2 hyperintensity). Interobserver agreement was assessed before reaching consensus. Significant ancillary features were identified using random forest analysis. The impact of incorporation of significant ancillary features on diagnostic performance for incomplete pathologic necrosis (IPN; pathologically viable tumor > 0 mm) was assessed using McNemar tests. RESULTS. Complete pathologic necrosis (CPN) was observed in 88 of 181 (48.6%) lesions. Interreader agreement was almost perfect for LI-RADS features of viability (κ = 0.92-0.97) and was substantial to almost perfect for ancillary features (κ = 0.73-0.94). Random forest analysis identified TP hypointensity (present in 8.0%, 25.0%, and 75.3% of lesions with CPN, viable tumor < 10 mm, and viable tumor ≥ 10 mm, respectively) and HBP hypointensity (9.2%, 25.0%, and 74.0%, respectively) as significant ancillary features. For detecting IPN, LR-TR (treatment response) Viable or LR-TR Equivocal had higher sensitivity than LR-TR Viable (71.0% vs 57.0%, respectively; p = .001) but had lower specificity (86.4% vs 94.3%, p = .02). However, LR-TR Viable or LR-TR Equivocal and TP hypointensity showed higher sensitivity than LR-TR Viable (64.5% vs 57.0%, p = .02) without a significantly different specificity (90.9% vs 94.3%, p = .25). LR-TR Viable or LR-TR Equivocal and HBP hypointensity also showed higher sensitivity than LR-TR Viable (65.6% vs 57.0%, p = .01) without a significantly different specificity (90.8% vs 94.3%, p = .25). CONCLUSION. TP hypointensity and HBP hypointensity increase the sensitivity of LI-RADS treatment response algorithm for viable tumor without lowering specificity. CLINICAL IMPACT. The two identified ancillary features may improve tumor viability assessment and planning of additional therapies after LRT for HCC.

Immune Responses Following Locoregional Treatment for Hepatocellular Carcinoma: Possible Roles of Adjuvant Immunotherapy.

Hepatocellular carcinoma (HCC) is a common cause of cancer-related deaths worldwide. Unlike other types of cancer, HCC can be treated with locoregional treatments (LRTs) such as radiofrequency ablation (RFA) or transarterial chemoembolization (TACE). However, recurrences following LRTs are common, and strategies to improve long-term outcomes need to be developed. The exhaustion of anti-tumor immunity in HCC has been well established in many reports and the immunomodulatory effects of LRTs (enhancement of tumor antigen-specific T cell responses after RFA, reduction of effector regulatory T cells after TACE) have also been reported in several previous studies. However, a comprehensive review of previous studies and the possible roles of immunotherapy following LRTs in HCC are not known. In this review, we discuss the immunological evidence of current clinical trials using LRTs and combined immunotherapies, and the possible role of this strategy.

Low serum magnesium concentration is associated with the presence of viable hepatocellular carcinoma tissue in cirrhotic patients

This study aimed to ascertain, for the first time, whether serum magnesium (Mg) concentration is affected by the presence of hepatocellular carcinoma (HCC). We retrospectively enrolled consecutive cirrhotic patients with a diagnosis of HCC (n = 130) or without subsequent evidence of HCC during surveillance (n = 161). Serum levels of Mg were significantly (P < 0.001) lower in patients with HCC than in those without (median [interquartile range]: 1.80 [1.62–1.90] mg/dl vs. 1.90 [1.72–2.08] mg/dl). On multivariate logistic regression, low serum Mg was associated with the presence of HCC (OR 0.047, 95% CI 0.015–0.164; P < 0.0001), independently from factors that can influence magnesaemia and HCC development. In a subset of 94 patients with HCC, a linear mixed effects model adjusted for confounders showed that serum Mg at diagnosis of HCC was lower than before diagnosis of the tumor (β = 0.117, 95% CI 0.039–0.194, P = 0.0035) and compared to after locoregional treatment of HCC (β = 0.079, 95% CI 0.010–0.149, P = 0.0259), with two thirds of patients experiencing these changes of serum Mg over time. We hypothesize that most HCCs, like other cancers, may be avid for Mg and behave like a Mg trap, disturbing the body’s Mg balance and resulting in lowering of serum Mg levels.

Immune changes linked to locoregional treatment of hepatocellular carcinoma

Immune changes linked to locoregional treatment of hepatocellular carcinoma

Abstract No. 571 Circulating cell-free RNA in plasma enables early detection of acute response to ablation and transarterial therapies for hepatocellular carcinoma

To identify circulating molecular signatures in blood samples that reflect an acute response to locoregional treatment of hepatocellular carcinoma (HCC). We hypothesize that the baseline cell-free RNA (cfRNA) profile in plasma will change with treatment and that longitudinal changes will detect tumor response and recurrence earlier than medical imaging.