Impact of Sarcopenia and Serum Creatinine on Clinical Outcomes after Tace in Hepatocellular Carcinoma.

Transarterial Radioembolization for Hepatocellular Carcinoma: Who, When… and Y(90)?

Chemoembolization and Radioembolization for Hepatocellular Carcinoma

To elucidate the role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) imaging as an independent prognostic factor in hepatocellular carcinoma (HCC). A total of 104 patients with newly diagnosed HCC who underwent 18F-FDG-PET/CT imaging from 2009 to 2014 were reviewed retrospectively. The ratio of the maximal tumor standardized uptake value (SUV) to the mean mediastinum SUV (TSUVmax/MSUVmean) was evaluated as the predictive factor. A high TSUVmax/MSUVmean ratio (≥3.1) was significantly associated with tumor burden indices, including α-fetoprotein (p<0.001), amino transaminase (AST) (p=0.007), tumor size (p=0.043), Tumor, Node, and Metastasis (TNM) stage (p<0.001), and Barcelona Clinic Liver Cancer (BCLC) staging (p<0.001). The mortality rate was higher (48.1% vs. 23.1%, p<0.001) in patients with a high TSUVmax/MSUVmean ratio (≥3.1). Among the 47 patients who underwent transarterial chemoembolization (TACE), patients with a high TSUVmax/MSUVmean ratio (≥3.1) were more likely to have recurrence following TACE (18/19 vs. 18/28, p=0.016). A high TSUVmax/MSUVmean ratio on 18F-FDG-PET/CT imaging can serve as an independent prognostic factor in HCC and may predict tumor recurrence after TACE.

New Developments in the Treatment of Hepatocellular Carcinoma: The Concept of Adjuvant and Neoadjuvant Chemotherapy

e15639 Background: Tyrosine kinase inhibitors (TKI) are important treatment options for unresectable hepatocellular carcinoma (HCC). The survival benefit of sorafernib was demonstrated not only in advanced stage but also for BCLC-B intermediate stage who are refractory to transcatheter arterial chemoembolization by OPTIMIS study. Skeletal muscle mass depletion (Myopenia) is a poor prognostic factor in HCC treated by resection or loco-reginal ablation, but its effect on survival in TKI treated patients, especially in those within BCLC-B stage remains unclear. The aim of the present study is to elucidate the impact of myopenia on survival among HCC treated with sorafenib, especially in BCLC-B stage. Methods: In 213 patients who started treatment with sorafenib between 2009 and 2016, myopenia at baseline was determined by using skeletal muscle index calculated from CT images of the third lumber vertebra level. The impact of myopenia on survival was analyzed in whole patients, after stratification by BCLC stage, and after matching for backgrounds within BCLC-B patients. Results: The median survival in whole, BCLC-C, and –B was 13.7, 8.7 and 15.2 months, respectively. Myopenia was not a significant prognostic factor in whole patients and in BCLC-C stage. However, among BCLC-B patients (n = 104), survival was significantly better in patients with no myopenia (p = 0.05). Among them, 85 patients who continued sorafenib for more than 8 weeks were extracted and those with or without myopenia were matched for backgrounds by propensity score. Backgrounds including etiology, Child-Pugh score, BMI, AFP and PIVKA-Ⅱwas not different between myopenia (n = 30) and no myopenia group (n = 30) after matching. The overall survival at 6-, 12-, and 24-months was 96%, 74%, and 62% in no myopenia group which was significantly better compared to 89%, 64%, and 28% in myopenia group (p = 0.019). The hazard ratio was 2.12 (95% CI 1.11-4.03). Conclusions: Absence of myopenia predicts favorable outcome in sorafenib treated HCC patients within BCLC-B intermediate stage.

Background Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) serves as a tumor suppressor in hepatocellular carcinoma (HCC), but the correlation between the expression of LHPP and the clinical parameters of oncogenic progression is still not well defined. This study is to reveal the correlation between the expression of LHPP in HCC and their clinical parameters. Methods Immunohistochemical analysis was used to assess the correlation between the expression of LHPP and the clinical parameters of HCC. Expressions of LHPP in HCC tissues and cultured HCC cells were detected by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). LHPP, gamma-glutamyl transferase (GGT), and α-fetoprotein (AFP) expression levels in blood or HCC tissues were detected by enzyme-linked immunosorbent assay (ELISA). The Spearman rank correlation coefficient was used to evaluate the correlation of the expression of LHPP and the clinical index of HCC. Correlation of survival and expression of LHPP were analyzed using the Kaplan-Meier method and the log-rank test. Results Expressions of LHPP in HCC tissues were significantly downregulated than their paired adjacent normal tissues. A significant positive correlation was found between the cytoplasm and nuclear expression of LHPP in both HCC and their paired adjacent normal tissues. The expression of LHPP negatively correlated with the levels of GGT in the cytoplasm of adjacent tissues and with the AFP level in the nucleus of HCC cells. Relative levels of LHPP in HCC tissues were markedly lower than those of the paired adjacent normal tissues. Relative levels of LHPP in LO-2 cells were higher than those of HepG2, BEL-7404, and SMMC-7721 cell lines. The overall survival and DSF survival of patients with the high expression of LHPP were much higher than those with the low expression of LHPP in paired adjacent normal tissue. Conclusions LHPP is associated with the AFP level and acts as a good prognostic factor in HCC.

Complex Therapeutic Strategies for Hepatocellular Carcinoma: Expanding Criteria.

e15635 Background: Transarterial chemoembolization (TACE) is currently the first-line treatment for patients with intermediate (BCLC stage B) hepatocellular carcinoma (HCC). However, the prognosis of patients with intermediate HCC remains unsatisfactory, because TACE was limited by its lack of ability to achieve complete tumor necrosis. In this study, we retrospectively compare the outcome of TACE with or without microwave ablation (MWA) in the treatment of intermediate HCC. Methods: Included in this study were 140 patients with intermediate stage HCC who underwent initial TACE and were potentially amendable for MWA (the sum of the size of the largest tumor in centimeters and the number of tumors should be no more than nine; and a total tumor diameter ≤11 cm) between January 2005 and February 2015. 75 patients were treated with following MWA (TACE-MWA), and the remaining 65 patients were treated with TACE alone. Cumulative overall survival (OS) and progression-free survival (PFS) rates were compared. Results: The respective 1-, 3-, and 5-year OS rates were 80%, 30%, and 20% in the TACE group; and 96%, 69%, and 48% in the TACE-MWA group (Fig. 2). The OS was statistically significantly better in the TACE-MWA group compared with the TACE group (P &lt; 0.001). The respective 1-, 3-, and 5-year PFS rates were 53%, 13%, and 0% in the TACE group; and 59%, 27%, and 17% in the TACE-MWA group (Fig. 3B). PFS rates between the two groups did not differ significantly (P = 0.069). Conclusions: MWA following initial TACE prolongs OS and PFS of patients with potentially amendable intermediate HCC.

We conducted a prospective study to evaluate the significance of simultaneous measurement of 3 currently used tumor markers in the evaluation of tumor progression and prognosis of patients with hepatocellular carcinoma (HCC). Three tumor markers for HCC, alpha-fetoprotein (AFP), Lens culinaris agglutinin A-reactive fraction of AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP), were measured in the same serum samples obtained from 685 patients at the time of initial diagnosis of HCC. Positivity for AFP >20 ng/dL, AFP-L3 >10% of total AFP, and/or DCP >40 mAU/mL was determined. In addition, tumor markers were measured after treatment of HCC. Of the 685 patients, 337 (55.8%) were positive for AFP, 206 (34.1%) were positive for AFP-L3, and 371 (54.2%) were positive for DCP. In a comparison of patients positive for only 1 tumor marker, patients positive for AFP-L3 alone had a greater number of tumors, whereas patients positive for DCP alone had larger tumors and a higher prevalence of portal vein invasion. When patients were compared according to the number of tumor markers present, the number of markers present clearly reflected the extent of HCC and patient outcomes. The number of markers present significantly decreased after treatment. Tumor markers AFP-L3 and DCP appear to represent different features of tumor progression in patients with HCC. The number of tumor markers present could be useful for the evaluation of tumor progression, prediction of patient outcome, and treatment efficacy.

BACKGROUNDMicrovascular invasion (MVI) is an important prognostic factor in hepatocellular carcinoma (HCC), but its preoperative prediction remains challenging.AIMTo develop and validate a 2.5-dimensional (2.5D) deep learning-based multi-instance learning (MIL) model (MIL signature) for predicting MVI in HCC, evaluate and compare its performance against the radiomics signature and clinical signature, and assess its prognostic predictive value in both surgical resection and transcatheter arterial chemoembolization (TACE) cohorts.METHODSA retrospective cohort consisting of 192 patients with pathologically confirmed HCC was included, of whom 68 were MVI-positive and 124 were MVI-negative. The patients were randomly assigned to a training set (134 patients) and a validation set (58 patients) in a 7:3 ratio. An additional 45 HCC patients undergoing TACE treatment were included in the TACE validation cohort. A modeling strategy based on computed tomography arterial phase images was implemented, utilizing 2.5D deep learning in combination with a MIL framework for the prediction of MVI in HCC. Moreover, this method was compared with the radiomics signature and clinical signatures, and the predictive performance of the various models was evaluated using receiver operating characteristic curves and decision curve analysis (DCA), with DeLong’s test applied to compare the area under the curve (AUC) between models. Kaplan-Meier curves were utilized to analyze differences in recurrence-free survival (RFS) or progression-free survival (PFS) among different HCC treatment cohorts stratified by MIL signature risk.RESULTSMIL signature demonstrated superior performance in the validation set (AUC = 0.877), significantly surpassing the radiomics signature (AUC = 0.727, P = 0.047) and clinical signature (AUC = 0.631, P = 0.004). DCA curves indicated that the MIL signature provided a greater clinical net benefit across the full spectrum of risk thresholds. In the prognostic analysis, high- and low-risk groups stratified by the MIL signature exhibited significant differences in RFS within the surgical resection cohort (training set P = 0.0058, validation set P = 0.031) and PFS within the TACE treatment cohort (P = 0.045).CONCLUSIONMIL signature demonstrates more accurate MVI prediction in HCC, surpassing radiomics signature and clinical signature, and offers precise prognostic stratification, thereby providing new technical support for personalized HCC treatment strategies.

Evaluation of Pretreatment Albumin-Bilirubin Grade as a Better Prognostic Factor than Child-Pugh Classification in Hepatocellular Carcinoma Patients Administered Transarterial Chemoembolization Combined with Radiotherapy

Hepatocellular carcinoma (HCC) is an aggressive malignant neoplasm that requires liver transplantation (LT). Despite patients with HCC being prioritized by most organ allocation systems worldwide, they still have to wait for long periods. Locoregional therapies (LRTs) are employed as bridging therapies in patients with HCC awaiting LT. Although largely used in the past, transarterial embolization (TAE) has been replaced by transarterial chemoembolization (TACE). However, the superiority of TACE over TAE has not been consistently shown in the literature. To compare the outcomes of TACE and TAE in patients with HCC awaiting LT. All consecutive patients with HCC awaiting LT between 2011 and 2020 at a single center were included. All patients underwent LRT with either TACE or TAE. Some patients also underwent percutaneous ethanol injection (PEI), concomitantly or in different treatment sessions. The choice of LRT for each HCC nodule was determined by a multidisciplinary consensus. The primary outcome was waitlist dropout due to tumor progression, and the secondary outcome was the occurrence of adverse events. In the subset of patients who underwent LT, complete pathological response and post-transplant recurrence-free survival were also assessed. Twelve (18.5%) patients in the TACE group (only TACE and TACE + PEI; n = 65) and 3 (7.9%) patients in the TAE group (only TAE and TAE + PEI; n = 38) dropped out of the waitlist due to tumor progression (P log-rank test = 0.29). Adverse events occurred in 8 (12.3%) and 2 (5.3%) patients in the TACE and TAE groups, respectively (P = 0.316). Forty-eight (73.8%) of the 65 patients in the TACE group and 29 (76.3%) of the 38 patients in the TAE group underwent LT (P = 0.818). Among these patients, complete pathological response was detected in 7 (14.6%) and 9 (31%) patients in the TACE and TAE groups, respectively (P = 0.145). Post-LT, HCC recurred in 9 (18.8%) and 4 (13.8%) patients in the TACE and TAE groups, respectively (P = 0.756). Posttransplant recurrence-free survival was similar between the groups (P log-rank test = 0.71). Dropout rates and posttransplant recurrence-free survival of TAE were similar to those of TACE in patients with HCC. Our study reinforces the hypothesis that TACE is not superior to TAE as a bridging therapy to LT in patients with HCC.

The emerging questionable benefit of sorafenib as a neo-adjuvant in HCC patients treated with Y-90 radioembolization pending liver transplantation

MicroRNAs as effective prognostic biomarkers in transarterial chemoembolization procedure for hepatocellular carcinoma patients – Correspondence

Transarterial chemoembolization (TACE) is recommended as the first-line treatment in intermediate-stage patients with hepatocellular carcinoma (HCC) or as a palliative treatment modality in advanced patients. However, tumor control usually requires multiple TACE interventions due to the presence of residual and recurrent lesions. Elastography can provide information about tumor stiffness (TS) to predict tumor residual or recurrence. In this study, we aimed to analyze the effects of TACE on HCC stiffness using ultrasound elastography (US-E). We investigated whether quantifying TS using US-E could predict the recurrence of HCC. This retrospective cohort study included 116 patients undergoing TACE to treat HCC. US-E was performed to measure the tumor's elastic modulus within 3 days before TACE, in the 2 days after the intervention, and at the 1-month follow-up. The known prognostic factors of HCC were also analyzed. The average TS before TACE was 40.1±14.36 kPa, and the average TS 1 month after TACE was 19.3±9.80 kPa. The mean progression-free survival (PFS) was 39.129 months, and the 1-, 3-, and 5-year PFS rates were 81.0%, 56.9%, and 37.9%, respectively. The mean overall survival (OS) was 48.552 months, and the 1-, 3-, and 5-year OS rates of patients with malignant hepatic tumors were 95.7%, 75.0%, and 49.1%, respectively. Tumor number, tumor location, TS before TACE, and TS 1 month after TACE were significant predictive factors for OS (P=0.02, P=0.03, P<0.001, and P<0.001, respectively). Rank correlation analysis and linear regression revealed that a higher TS before or 1 month after TACE was negatively associated with PFS. The reduction ratio in TS before and 1 month after therapy was positively associated with PFS. The optimal cutoff TS value was set at 46 and 24.5 kPa before and 1 month after TACE according to the optimal Youden index. Kaplan-Meier survival analyses demonstrated that the 2 groups had significant differences in OS and PFS and that a higher TS was positively correlated with OS and PFS. Our results verify that US-E provides additional information to characterize the tumoral stiffness of HCC. These findings indicate that US-E is a valuable tool for evaluating the tumor response after TACE therapy in patients. TS can also be an independent prognostic factor. Patients with a high TS had a higher risk of recurrence and a worse survival time.