Major Portal Vein Research Articles

Additional Hepatic Arterial Infusion Chemotherapy to Sorafenib Was Cost-Effective for Hepatocellular Carcinoma with Major Portal Vein Tumor Thrombosis.

The combination of sorafenib and hepatic arterial infusion chemotherapy (SoHAIC) has shown to enhance overall survival rates in patients with advanced hepatocellular carcinoma and major portal vein tumor thrombosis (HCC-Vp3-4) compared to sorafenib alone. Our objective was to evaluate the cost-effectiveness of SoHAIC versus sorafenib for the treatment of HCC-Vp3-4, taking into account the viewpoint of Chinese healthcare payers. This pharmacoeconomic study employed a Markov model to assess the cost-effectiveness of treating HCC-Vp3-4 with SoHAIC in comparison to sorafenib. The patient characteristics were drawn from individuals from the trial conducted between June 2017 and November 2019, with cost and health value data sourced from published literature. The primary outcome measure in this research was the incremental cost-effectiveness ratio (ICER), which indicates the additional cost per quality-adjusted life year (QALY). The willingness-to-pay (WTP) threshold per QALY was set at $30,492.00. Furthermore, 1-way sensitivity and probabilistic sensitivity analyses were carried out to validate the consistency of the results. In the baseline scenario, sorafenib resulted in 0.42 QALY at a cost of $10,507.89, while SoHAIC generated 1.66 QALY at a cost of $32,971.56. When comparing SoHAIC to sorafenib, the ICER was $18,237.20 per QALY, which was below the WTP threshold per QALY. Furthermore, the 1-way sensitivity analysis demonstrated that the ICER remained within the WTP threshold despite fluctuations in variables. In the probabilistic sensitivity analysis, SoHAIC had a 98.8% probability of being cost-effective at the WTP threshold, considering a wide range of parameters. In this cost-effectiveness evaluation, SoHAIC demonstrated cost-effectiveness over sorafenib for HCC with major portal vein tumor thrombosis, as observed from the perspective of a Chinese payer.

Lenvatinib plus drug-eluting bead transarterial chemoembolization with/without hepatic arterial infusion chemotherapy for hepatocellular carcinoma larger than 7 cm with major portal vein tumor thrombosis: a multicenter retrospective cohort study.

The management of hepatocellular carcinoma (HCC) with high tumor burden and major portal vein tumor thrombosis (PVTT) remains a great challenge. We aimed to investigate the efficacy and safety of lenvatinib plus drug-eluting bead transarterial chemoembolization (DEB-TACE) and hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, fluorouracil and leucovorin (Len+DEB-TACE+HAIC) versus lenvatinib plus DEB-TACE (Len+DEB-TACE) for HCC > 7.0cm accompanied with major PVTT. This multicenter retrospective cohort study evaluated consecutive patients with HCC (> 7.0cm) and major PVTT who received Len+DEB-TACE+HAIC (Len+DEB-TACE+HAIC group) or Len+DEB-TACE (Len+DEB-TACE group) between July 2019 and June 2021 from eight institutions in China. Objective response rate (ORR), time to progression (TTP), overall survival (OS), and treatment-related adverse events (TRAEs) were compared between the two groups by propensity score-matching (PSM). A total of 205 patients were included. After PSM, 85-paired patients remained in the study cohorts. Patients in the Len+DEB-TACE+HAIC group had higher ORR (61.2% vs. 34.1%, P < 0.001), longer TTP (median, 9.8 vs. 5.9 months, P < 0.001), and prolonged OS (median, 16.7 vs. 12.5 months, P < 0.001) than those in the Len+DEB-TACE group. The ORR and TTP of both intrahepatic tumor (ORR: 64.7% vs. 36.5%, P < 0.001; median TTP: 10.7 vs. 7.0 months, P < 0.001) and PVTT (ORR: 74.1% vs. 47.1%, P < 0.001; median TTP: 17.4 vs. 7.6 months, P < 0.001) were better in the Len+DEB-TACE+HAIC group than the Len+DEB-TACE group. The frequency of grade 3-4 TRAEs in the Len+DEB-TACE+HAIC group were comparable to those in the Len+DEB-TACE group (38.8% vs. 34.1%, P = 0.524). The addition of HAIC to Len+DEB-TACE significantly improved ORR, TTP, and OS over Len+DEB-TACE with an acceptable safety profile for large HCC with major PVTT.

Proton Beam Therapy for Treating Patients with Hepatocellular Carcinoma with Major Portal Vein Tumor Invasion: A Single Center Retrospective Study.

Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) has a poor prognosis and is generally not indicated for surgery. Proton beam therapy (PBT) may offer an alternative treatment. In this study, long-term outcomes were examined in 116 patients (median age 66 years, 100 males) with HCC with advanced PVTT (Vp3 or Vp4) who received PBT from April 2008 to March 2018. Of these patients, 63 received PBT as definitive treatment and 53 as palliative treatment. The representative dose was 72.6 Gy (RBE) in 22 fractions. Eight patients died in follow-up, including 72 due to tumor progression. The 5-year overall survival (OS) rate was 18.0% (95% CI 9.8-26.2%) and the 5-year local control (LC) rate was 86.1% (74.9-97.3%). In multivariate analyses, performance status and treatment strategy were significantly associated with OS. The median follow-up period for survivors with definitive treatment was 33.5 (2-129) months, and the 5-year OS rate was 25.1% (12.9-37.3%) in these cases. The median survival time after definitive irradiation was >20 months. The 5-year OS rate was 9.1% (0-19.7%) for palliative irradiation. These results compare favorably with those of other therapies and suggest that PBT is a useful option for cases of HCC with advanced PVTT that cannot undergo surgery, with an expected survival benefit and good local control. Determining the optimal indication for this treatment is a future challenge.

Hepatic arterial infusion chemotherapy, lenvatinib plus programmed cell death protein-1 inhibitors: A promising treatment approach for high-burden hepatocellular carcinoma.

Hepatic arterial infusion chemotherapy (HAIC) has demonstrated remarkable local therapeutic efficacy in treating patients with large unresectable hepatocellular carcinoma (HCC). Additionally, the combination of lenvatinib and programmed cell death protein-1 (PD-1) inhibitors has demonstrated promising antitumor effects in unresectable HCC. Therefore, we conducted a retrospective analysis to evaluate the efficacy and safety of combining HAIC with lenvatinib and PD-1 inhibitors as a first-line therapeutic approach in high-burden HCC patients. We conducted a retrospective analysis on patients diagnosed with high-burden HCC who had major portal vein tumor thrombosis (Vp3 and Vp4) or tumor occupancy exceeding 50% of the liver. These patients received a first-line treatment consisting of HAIC with a combination of 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX), along with lenvatinib and PD-1 inhibitors between November 2020 and June 2023. The primary endpoints of this study included progression-free survival (PFS) and overall survival (OS), while the secondary endpoints were objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs). Ninety-one patients were enrolled in this study, with a median PFS of 8.8 months (95% confidence interval [CI]: 5.75-11.78) and a median OS of 14.3 months (95% CI: 11.23-17.31). According to RECIST 1.1 criteria, the ORR was 52.7%, and DCR was 95.6%. According to the mRECIST criteria, the ORR was 72.5%, and the DCR was 96.5%. Among all patients, 86 (94.5%) experienced TRAEs, and there were no instances of treatment-related deaths. The combination of HAIC-FOLFOX with lenvatinib and PD-1 inhibitors as a first-line therapy has exhibited notable therapeutic efficacy and well-tolerated adverse events among patients with high-burden HCC.

A Novel Method Using Gadolinium-Ethoxybenzyl Diethylenetriamine Pentaacetate Acid-Enhanced Magnetic Resonance Imaging for Predicting Post-Hepatectomy Liver Failure in Hepatocellular Carcinoma Patients with a Major Portal Vein Tumor Thrombus

Introduction: The usefulness of gadolinium-ethoxybenzyl diethylenetriamine pentaacetate acid-enhanced magnetic resonance imaging (EOB-MRI) in assessing the functional future remnant liver volume (fFRLV) to predict post-hepatectomy liver failure (PHLF) has been previously reported. Herein, we evaluated the efficacy of this technique in patients with hepatocellular carcinoma (HCC) with a major portal vein tumor thrombus (PVTT). Methods: This study included 21 patients with PVTT in the ipsilateral first-order branch (Vp3) and 30 patients with PVTT in the main trunk/contralateral branch (Vp4). To evaluate fFRLV, the signal intensity (SI) of the remnant liver was determined on T1-weighted images, using both conventional and newly developed methods. The fFRLV was calculated using the SI of the remnant liver and muscle, remnant liver volume, and body surface area. Preoperative factors predicting PHLF (≥grade B) in HCC patients with Vp3/4 PVTT were evaluated. Results: In the Vp3 group, we found fFRLV area under the receiver-operating characteristic curves (AUCs) above 0.70 (AUC = 0.875, 0.750) using EOB-MRI results calculated using either the plot or whole method. None of the parameters in the Vp4 group had an AUC greater than 0.70. Conclusion: The fFRLV calculated by EOB-MRI using the whole method can be as useful as the conventional method in predicting PHLF (≥grade B) for HCC patients with Vp3 PVTT.

Assessment of liver function by gadoxetic acid avidity in MRI in a model of rapid liver regeneration in rats

BackgroundThis animal study investigates the hypothesis of an immature liver growth following ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) by measuring liver volume and function using gadoxetic acid avidity in magnetic resonance imaging (MRI) in models of ALPPS, major liver resection (LR) and portal vein ligation (PVL). MethodsWistar rats were randomly allocated to ALPPS, LR or PVL. In contrast-enhanced MRI scans with gadoxetic acid (Primovist®), liver volume and function of the right median lobe (=future liver remnant, FLR) and the deportalized lobes (DPL) were assessed until post-operative day (POD) 5. Liver functionFLR/DPL was defined as the inverse value of time from injection of gadoxetic acid to the blood pool-corrected maximum signal intensityFLR/DPL multiplied by the volumeFLR/DPL. ResultsIn ALPPS (n = 6), LR (n = 6) and PVL (n = 6), volumeFLR and functionFLR increased proportionally, except on POD 1. Thereafter, functionFLR exceeded volumeFLR increase in LR and ALPPS, but not in PVL. Total liver function was significantly reduced after LR until POD 3, but never undercuts 60% of its pre-operative value following ALPPS and PVL. DiscussionThis study shows for the first time that functional increase is proportional to volume increase in ALPPS using gadoxetic acid avidity in MRI.

Advanced hepatocellular carcinoma with major portal vein invasion: Therapeutic outcomes of hepatic arterial infusion chemotherapy vs concurrent radiotherapy.

Hepatocellular carcinoma (HCC) with major portal vein invasion (MPVI) presents very poor outcomes. Hepatic artery infusion chemotherapy (HAIC) and radiation therapy (RT) have both been found to be effective for advanced HCC. In this retrospective study, we compared the therapeutic outcomes of our "new" HAIC regimen with and without concurrent RT, before and after propensity score matching (PSM) in treating HCC patients with MPVI. One hundred forty patients with MPVI received HAIC alone and 35 patients underwent concurrent HAIC and RT during a 16-year period. The left subclavian artery was adopted as the entry site for a temporary catheter placement for a 5-day chemoinfusion. The Modified Response Evaluation Criteria in Solid Tumors (mRECIST) was adopted to assess the objective response rate (ORR). The Kaplan-Meier curve was used to calculate progression-free survival (PFS) and overall survival (OS) between the two groups. Univariate and multivariate analyses by Cox regression model were used to assess hazard ratios. Of the 140 patients with Child-Pugh A liver function, the median OS was 17.0 months. In the initial cohort, higher ORR and PFS were found in the concurrent RT group than in the HAIC alone group (80% vs 66.4% and 9 vs 8 months, respectively) but shorter OS (10.5 vs 14.5 months, p = 0.039) was observed. After PSM, the OS was 10 and 15 months ( p = 0.012), respectively. Multivariable Cox regression analysis revealed that the significant factors for adjusting hazard ratios for OS were Child-Pugh classification, alpha fetal protein (AFP) level, and hepatic vein invasion. HAIC is an effective treatment for advanced HCC patients with MPVI. Concurrent HAIC and full-dose RT were associated with worse clinical outcomes.

Simple Scoring System for Esophagogastric Varices Prediction in Hepatocellular Carcinoma Patients without Liver Stiffness Evaluation

Introduction: For predicting esophagogastric varices (EGVs), the Virtual Baveno VII Consensus Workshop has proposed a combination of liver stiffness determination and platelet count measurement using a FibroScan^®. However, FibroScan^® is not available at all institutions. The present study aimed to develop a simple method to predict development of EGV using only general blood examination results. Materials and Methods: A total of 1,090 hepatocellular carcinoma patients were enrolled, after excluding 956 with major portal vein tumor thrombus (Vp3/Vp4) or without upper gastrointestinal endoscopy examination results available. Those with EGV (≥ grade F2) or a history of treatment for the condition were defined as positive for significant EGV, and then clinical factors were retrospectively evaluated to determine indicators of occurrence. Results: Logistic multivariate analysis showed platelet count (≤12 × 10⁴/μL) (odds ratio [OR] 3.79, p < 0.001), mALBI grade 2a (OR 1.52, p = 0.036), and mALBI 2b or 3 (OR 3.46, p < 0.001) as significant predictive factors. Based on the OR values, platelet count (≤12 × 10⁴/μL) and mALBI grade 2b/3 were each assigned 2 points and mALBI 2a was given 1 point, with the result termed recommendation for EGV screening (REGS) score. Significant EGV occurrence was noted in 2.9% (9/311) of the patients with a REGS score 0, 11.0% (13/118) with a score 1, 19.3% (53/274) with a score 2, 29.5% (39/132) with a score 3, and 38.0% (97/255) with a score 4 (p < 0.001). Conclusion: The findings indicate that REGS score can provide useful predictive information for development of significant EGV without the need for special equipment such as a FibroScan^®.

Liver-Directed Combined Radiotherapy for Downstaging of the Milan Advanced Hepatocellular Carcinoma Converting to Liver Transplantation

Recent success of combined immunotherapy sheds a light to the future of advanced hepatocellular carcinoma patients but still remains as a palliative setting. The best oncologic outcome for HCC can be obtained by curative surgery either by resection or liver transplantation (LT). Efficacy of liver-directed combined radiotherapy (LD-CRT) for downstaging and subsequent surgical resection in locally advanced HCC had been reported earlier by our team. In this study, we investigated the role of LD-CRT as a downstaging strategy for converting advanced hepatocellular carcinoma to LT. We reviewed 55 hepatocellular carcinoma patients who had undergone downstaging LD-CRT and subsequent liver transplantation from January 2009 to February 2022. Patients within Milan criteria at the time of receiving radiotherapy were excluded and clinical characteristics and histopathology of explant liver were evaluated. The overall survival and disease-free survival were assessed using the Kaplan-Meier method RESULTS: The median follow-up period was 48.6 months (range 6.9 - 151.7 months). Of 55 patients, 24 (43.6%) were treatment naïve. At the time of RT, 36 patients presented large tumor (tumor diameter >5 cm) or multiple lesions (>3 lesions), 37 with major vessel involvement or portal vein tumor thrombosis, and 7 with extrahepatic lesion. LD-CRT was given as localized concurrent chemoradiation (CCRT) for 41 patients (74.5%) and transarterial chemoembolization (TACE) plus RT for 10 patents (18.2%). Substantial downstaging has been achieved in 38 (69%) patients with initially over the Milan to within Milan. Specifically, 29 of 37 patients initially with major vessel invasion or with tumor thrombosis were successfully converted to microscopic vessel invasion or tumor thrombus-free status in explant liver. 5-year overall survival was 68.1% and 2-year disease-free survival was 51%, respectively. Recurrence after transplantation was observed in 18 patients (4 intrahepatic recurrence and 14 extrahepatic metastasis) and the majority (14/18) occurred within 2 years. Liver-directed combined radiotherapy as a downstaging strategy for liver transplantation achieved favorable oncologic outcomes in advanced hepatocellular carcinoma patients. This study suggests that active adoption of radiotherapy needs full consideration for locally advanced HCC patients, opening a chance for curative LT.

Reference Values for Dimensions of Major Portal and Systemic Intra-abdominal Veins of Children on Computed Tomography

Reference Values for Dimensions of Major Portal and Systemic Intra-abdominal Veins of Children on Computed Tomography

Transarterial interventional therapy combined with tyrosine kinase inhibitors with or without anti-PD-1 antibodies as initial treatment for hepatocellular carcinoma with major portal vein tumor thrombosis: a single-center retrospective study.

Transarterial interventional therapy combined with tyrosine kinase inhibitors (TKIs) and anti-Pd-1 antibodies (triplet regimen) has shown promising results in advanced HCC. However, the clinical utility of the triplet regimen in patients with HCC and major portal vein tumor thrombosis (PVTT) remains unclear. This study compared the efficacy and safety of the triplet regimen versus transarterial interventional therapy combined with TKIs (double regimen) for such patients. Thirty-nine patients treated with the triplet regimen were retrospectively compared with 37 patients treated with the double regimen. The objective response rate (ORR), the response rate of PVTT treatment, and safety were observed; progression-free survival (PFS) and overall survival (OS) were assessed using the Kaplan‒Meier method and log-rank test. Predictors of survival were identified using multivariate analysis. Median OS and median PFS were significantly improved in the Triplet Group compared with the Double Group (482 vs. 310days; 208 vs. 85days). The ORR and the response rate of PVTT were significantly higher in the Triplet Group than in the Double Group (59% vs. 35%; 62% vs. 35%). There was no significant difference in the incidence of grade 3/4 adverse events between the two groups (33% vs. 21%). The most frequent grade 3/4 adverse events were thrombocytopenia (10%) in the Triplet Group and hand-foot syndrome (14%) in the Double Group. Multivariable analysis showed that treatment method and PVTT treatment response were significant predictors of OS. The triplet regimen showed superiority over the doublet regimen in improving OS and PFS and had acceptable safety in patients with HCC and major PVTT.

Expression of Peptidyl Arginine Deiminase 2 Is Closely Associated with Recurrence in Patients with Hepatocellular Carcinoma.

Peptidyl arginine deiminases (PAD) enzymes have been investigated in various cancers. Recently, PAD enzyme, in particular PAD2, has been further implicated in cancers. Although the expression of PAD2 was significantly higher in hepatocellular carcinoma (HCC) tissue, its diagnostic or prognostic role of PAD2 in HCC patients is unknown. This study investigated whether the expression of PAD2 affects recurrence and survival in HCC patients who underwent hepatic resection. One hundred and twenty-two HCC patients after hepatic resection were enrolled. The median follow-up was 41 months (range 1-213 months) in enrolled patients. To investigate an association between PAD2 expression level and the clinical characteristics of enrolled patients, the recurrence of HCC following surgical resection and survival of the patients were examined. Ninety-eight cases (80.3%) of HCC demonstrated a higher expression of PAD2. The expression of PAD2 was correlated with age, hepatitis B virus positivity, hypertension, and higher alpha-fetoprotein level. There was no association between PAD2 expression and sex, diabetes mellitus, Child-Pugh class, major portal vein invasion, HCC size or number. The recurrence rates in patients with lower PAD2 expression were higher than those with higher PAD2 expression. The cumulative survival rates of patients with higher PAD2 expression were better than those of patients with lower PAD2 expression, but it was not statistically significant. In conclusion, PAD2 expression is closely associated with recurrence of HCC patients following surgical resection.

Liver-directed combined radiotherapy for downstaging of over the Milan advanced hepatocellular carcinoma converting to liver transplantation.

561 Background: Recent success of combined immunotherapy sheds a light to the future of advanced hepatocellular carcinoma patients but still remains as a palliative setting. The best oncologic outcome for HCC can be obtained by curative surgery either by resection or liver transplantation (LT). Efficacy of liver-directed combined radiotherapy (LD-CRT) for downstaging and subsequent surgical resection in locally advanced HCC had been reported earlier by our team. In this study, we investigated the role of LD-CRT as a downstaging strategy for converting advanced hepatocellular carcinoma to LT. Methods: We reviewed 55 hepatocellular carcinoma patients who had undergone downstaging LD-CRT and subsequent liver transplantation from January 2009 to February 2022. Patients within Milan criteria at the time of receiving radiotherapy were excluded and clinical characteristics and histopathology of explant liver were evaluated. The overall survival and disease-free survival were assessed using the Kaplan-Meier method. Results: The median follow-up period was 48.6 months (range 6.9 – 151.7 months). Of 55 patients, 24 (43.6%) were treatment naïve. At the time of RT, 36 patients presented large tumor (tumor diameter &gt;5 cm) or multiple lesions (&gt;3 lesions), 37 with major vessel involvement or portal vein tumor thrombosis, and 7 with extrahepatic lesion. LD-CRT was given as localized concurrent chemoradiation (CCRT) for 41 patients (74.5%) and transarterial chemoembolization (TACE) plus RT for 10 patents (18.2%). Substantial downstaging has been achieved in 38 (69%) patients with initially over the Milan to within Milan. Specifically, 29 of 37 patients initially with major vessel invasion or with tumor thrombosis were successfully converted to microscopic vessel invasion or tumor thrombus-free status in explant liver. 5-year overall survival was 68.1% and 2-year disease-free survival was 51%, respectively. Recurrence after transplantation was observed in 18 patients(4 intrahepatic recurrence and 14 extrahepatic metastasis) and the majority (14/18) occurred within 2 years. Conclusions: Liver-directed combined radiotherapy as a downstaging strategy for liver transplantation achieved favorable oncologic outcomes in advanced hepatocellular carcinoma patients. This study suggests that active adoption of radiotherapy needs full consideration for locally advanced HCC patients, opening a chance for curative LT.

Cirrhotic and non-cirrhotic huge hepatocellular carcinoma (≥ 10cm): a comparative study of surgical management and follow-up treatment in a single institution.

Liver resection (LR) of huge hepatocellular carcinoma (HCC) has increasingly been regarded as a viable option of enhanced efficacy for patients, but most studies have focused on comparing various tumor sizes and the outcomes of surgery. The study aim was to evaluate the clinicopathologic characteristics and surgical outcomes of huge HCC with and without cirrhosis that underwent LR, and to delineate the treatment for recurrence. Sixty-three patients with huge HCC who underwent hepatectomy from 2010 to 2019 were enrolled and reviewed. Clinicopathological findings, surgical outcomes of the entire cohort, and differences between the cirrhotic and non-cirrhotic groups were analyzed. Forty patients (60.3%) had huge HCC with cirrhosis. Clinicopathological findings were not different between the two groups, except tumor size ≥ 15cm (40% in cirrhosis vs 17.4% in non-cirrhosis, p = 0.024) and major portal vein tumor thrombus were detected only in the cirrhosis group (11 patients, p = 0.006). Extended LR was performed in 13 cirrhotic patients (32.5%) and in 1 non-cirrhotic patient (4.4%) (p = 0.010). Operative data, postoperative complications including postoperative liver failure, and pattern of recurrence were not different between the two groups. For the entire cohort, mortality rate was 1.5%. The 1-, 3-, and 5-year overall survival rates (OS) were 81%, 54%, and 39%. Multivariate analysis showed resection margin ≥ 0.1cm was a good prognostic factor for OS (HR 0.247 (p = 0.017)). For tumor recurrence, local ablative treatment for liver recurrence and resection for lung recurrence provided good long-term outcomes. Although huge HCC with cirrhosis has been a more unfavorable tumor, LR still provided long-term survival with acceptable risk morbidity and mortality.

The Clinical Impact of Hepatic Arterial Infusion Chemotherapy New-FP for Hepatocellular Carcinoma with Preserved Liver Function.

Simple SummaryNew-FP is a regimen of hepatic arterial infusion chemotherapy for hepatocellular carcinoma (HCC). In the study, the regimen significantly prolonged the survival of patients with major portal vein tumor thrombus-HCC.Background: Systemic treatments are recommended for advanced hepatocellular carcinoma (HCC) in preserved liver function. However, their effects are unsatisfactory in some tumor conditions, particularly macrovascular invasion (MVI) including major portal vein tumor thrombus (PVTT). We compared the efficacy of hepatic arterial infusion chemotherapy (HAIC) regimens New-FP and sorafenib for various tumor conditions in preserved liver function. Methods: We retrospectively collected the data of 1709 patients with HCC who were treated with New-FP or sorafenib. Survival was assessed after propensity score matching. Subgroup analyses were conducted: cohort 1 (no MVI or extrahepatic spread (EHS)), cohort 2 (MVI only), cohort 3 (EHS only), cohort 4 (MVI and EHS), and cohort 5 (major PVTT). Results: The New-FP group had a longer median survival time (MST) than the sorafenib in the whole analysis (18 vs. 9 months; p < 0.0001). New-FP demonstrated a longer MST compared with sorafenib in cohort 2 and cohort 4. In cohort 5, the MST of the New-FP group was 16 months, while that of sorafenib was 6 months (p < 0.0001). For major PVTT-HCC, the response rate of New-FP was 73.0%. The MST of patients who achieved complete response with New-FP was 59 months. Conclusions: HAIC using New-FP is promising for patients with MVI- and major PVTT-HCC in preserved liver function.

727TiP A randomised phase III study of tremelimumab (T) plus durvalumab (D) with or without lenvatinib combined with concurrent transarterial chemoembolisation (TACE) versus TACE alone in patients (pts) with locoregional hepatocellular carcinoma (HCC): EMERALD-3

Locoregional therapies such as TACE are the most common treatments for pts with intermediate-stage HCC. Although TACE results in tumour responses, progression and recurrence are common, and median overall survival (OS) is approximately 20 months. TACE may alter the tumour microenvironment and serve as a primer for immunotherapies. The STRIDE regimen of Single Tremelimumab (high, priming 300-mg dose) Regular Interval Durvalumab (1500 mg every 4 weeks) improved OS vs sorafenib in pts with unresectable HCC (Abou-Alfa et al. J Clin Oncol 2022;40(suppl 4). Abs 379). Lenvatinib improved survival outcomes vs TACE in patients with unresectable HCC in a proof of concept study (Kudo et al. Cancers [Basel] 2019;11:1804). EMERALD-3 (NCT05301842) is a phase III, randomised, open-label, sponsor-blind, multicentre study assessing the efficacy and safety of STRIDE, with or without lenvatinib, given concurrently with TACE (either drug-eluting bead TACE or conventional TACE) vs TACE alone in pts with intermediate-stage HCC not amenable to curative therapy. 525 pts will be randomised 1:1:1 to Arm A (STRIDE plus lenvatinib [8 mg or 12 mg] once daily plus TACE), Arm B (STRIDE plus TACE), or Arm C (TACE alone). In Arm A and Arm B, the first TACE procedure will occur no earlier than 7 days following T and the first dose of D (and lenvatinib in Arm A); in Arm C the first TACE procedure will occur within 7 days post-randomisation. Eligible pts must have confirmed HCC (by imaging or histopathology) not amenable to curative therapy but eligible for embolisation, Child-Pugh score class A, Eastern Cooperative Oncology Group performance status of 0 to 1, measurable disease by modified Response Evaluation Criteria In Solid Tumours (mRECIST) and adequate organ and marrow function. Pts with visible baseline major portal vein invasion (Vp3/Vp4) or uncontrolled hypertension are excluded. The primary endpoint is progression-free survival (PFS) for Arm A vs Arm C by blinded independent review using RECIST v1.1. Additional endpoints include PFS for Arm B vs Arm C, OS, health-related quality of life and safety. NCT05301842. Medical writing support, under the direction of the authors, was provided by Brian Woolums, PhD, of CMC Connect, McCann Health Medical Communications, with funding from AstraZeneca, in accordance with Good Publications Practice (GPP3) guidelines. AstraZeneca.

Cellular Prion Protein Is Closely Associated with Early Recurrence and Poor Survival in Patients with Hepatocellular Carcinoma.

The cellular prion protein (PrPC) is known to play a role in cancer proliferation and metastasis. However, the role of PrPC expression in hepatocellular carcinoma (HCC) is unknown. This study investigated whether overexpression of PrPC affects recurrence after surgical resection and survival in HCC. A total of 110 HCC patients who underwent hepatic resection were included. They were followed up for a median of 42 months (range 1–213 months) after hepatectomy. The relationships between PrPC expression and the HCC histologic features, recurrence of HCC following surgical resection, and survival of the patients were examined. Seventy-one cases (64.5%) of HCC demonstrated higher expression of PrPC. The expression of PrPC was only correlated with diabetes mellitus. There was no association between PrPC expression and age, sex, hypertension, hepatitis B virus positivity, alcohol consumption, Child–Pugh class, major portal vein invasion, serum alpha-fetoprotein, and HCC size or number. The 1-year recurrence rates in patients with higher PrPC expression were higher than those with lower PrPC expression. The cumulative survival rates of patients with higher PrPC expression were significantly shorter than those of patients with lower PrPC expression. In conclusion, PrPC expression is closely associated with early recurrence and poor survival of HCC patients following surgical resection.

Sorafenib Plus Hepatic Arterial Infusion Chemotherapy versus Sorafenib for Hepatocellular Carcinoma with Major Portal Vein Tumor Thrombosis: A Randomized Trial

Background The prognosis of hepatocellular carcinoma (HCC) with major portal vein tumor thrombosis (PVTT) is dismal after standard treatment with sorafenib. Hepatic arterial infusion chemotherapy (HAIC) has been suggested for patients with HCC and major PVTT. Purpose To compare the efficacy and safety of sorafenib plus 3cir-OFF HAIC versus sorafenib alone for advanced HCC with major PVTT. Materials and Methods This phase II trial recruited systemic treatment-naïve patients with HCC and major PVTT (portal vein invasion grade Vp3 [first branch] and Vp4 [main trunk]) between June 2017 and November 2019. Patients were randomly assigned (1:1 ratio) to receive sorafenib (400 mg twice daily) plus 3cir-OFF HAIC (35 mg/m2 oxaliplatin [hours 0-2] followed by 600 mg/m2 5-fluorouracil [hours 2-24], days 1-3) with a standardized percutaneous port catheter system or sorafenib alone (400 mg twice daily) every 4 weeks. The primary end point was overall survival (OS). The secondary end points were objective response rate, progression-free survival (PFS), and safety. OS and PFS were assessed using the Kaplan-Meier method and log-rank test. Results The intent-to-treat population included 64 patients, with 32 in each group. The median OS was 16.3 months (95% CI: 0.0, 35.5) with sorafenib plus HAIC and 6.5 months (95% CI: 4.4, 8.6) with sorafenib alone (hazard ratio [HR] = 0.28; 95% CI: 0.15, 0.53; P < .001). A higher objective response rate (41% [n = 13] vs 3% [n = 1], P < .001) and a longer median PFS (9.0 months vs 2.5 months; HR = 0.26; 95% CI: 0.15, 0.47; P < .001) were observed in the sorafenib plus HAIC group. Grade 3 or 4 adverse events were more frequent in the sorafenib plus HAIC group, including diarrhea (n = 7 [22%] vs n = 5 [16%]), hand-foot syndrome (n = 6 [19%] vs n = 2 [6%]), and thrombocytopenia (n = 7 [22%] vs n = 0). Conclusion Sorafenib plus 3cir-OFF hepatic arterial infusion chemotherapy may be a promising treatment in patients with hepatocellular carcinoma and major portal vein tumor thrombosis because of the improved survival and an acceptable safety profile. Clinical trial registration no. NCT03009461 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Chung in this issue.

Increase of Liver Function and Volume after ALPPS Determined by MRI in a Rat Model

Introduction: It has been hypothesized that rapid increase of liver volume after ALPPS (Associating Liver Partition and Portal vein ligation for Staged hepatectomy) is not accompanied by a proportional increase of function. This study uses a rat models of major liver resection (LR), ALPPS and portal vein ligation (PVL) to test this hypothesis by measuring liver volume and function with contrast-enhanced magnetic resonance imaging (MRI). Methods: Wistar rats (200-250g) were randomly allocated to LR, ALPPS or PVL. T1-weighted MRI scans (7.0T MR Solutions,Guildford,UK) were performed until postoperative day 5. Uptake kinetics (2D-FLASH;TR/TE=589/8) of Primovist® (1mmol/kg,Bayer AG,Berlin, Germany) were measured in the future liver remnant (FLR) and spleen (blood pool). Liver volume was assessed during the excretion phase (2D-FLASH;TR/TE=4150/11; thickness 1mm). Liver function of the FLR was defined as the inverse value of time [min] from injection of Primovist® to maximum signal intensity multiplied by respective volume of the FLR [ccm]. Results: Percent increase of FLR volume overestimates FLR function at day 1 in all three, ALPPS, LR and PVL. From day 2, function and volume of the FLR increase proportionally in all procedures (Figure 1). Percent increase of liver function exceeds liver volume from day 2 until day 5 in ALPPS and LR, but not in PVL. Conclusion: This animal study rejects the hypothesis that functional increase is not proportional to volume increase in ALPPS. While function is impaired on day 1, ALPPS leads to a congruent increase of volume and function after day 1, similar to LR.

Laparoscopic Compared with Open Liver Resection in the Management of Colorectal Liver Metastases

Introduction: Laparoscopic liver resection (LLR) is increasingly adopted in the management of colorectal liver metastases (CRLM). This study compares perioperative and oncologic outcomes in LLR and open resection (OLR) for CRLM. Methods: Consecutive patients undergoing hepatectomy between 2009-2019 for CRLM at a single tertiary referral centre were prospectively studied. Univariable and multivariable logistic and Cox proportional hazards regression analysis was performed to determine the independent impact of operative approach on perioperative and oncologic outcome. Results: 273 patients were studied. LLR patients were more likely to be ASA-3 (58.0% vs 34.5%, P=0.016), older (65.4±9.4 vs 61.4±10.9 years, P=0.016) and have a greater Charlson comorbidity index (4.6±1.5 vs 4.0±1.4, P=0.008). LLR patients had less bilobar disease (18.0% vs 44.4%, P=0.001), were less likely to undergo major hepatectomy (6.0% vs 36.8%, P<0.001) or portal vein embolization (0.0% vs 10.8%, P=0.015), with increased non-anatomical resection (76.1% vs 66.0%, P=0.016). R0 resection rates were similar (86.0% vs 91.0%, P=0.310). Length of stay (median 7-days in both groups, P=0.313), readmission (4.0% vs 8.6%,P=0.275), and 30-day mortality (0.0% vs 1.8%, P=0.340) were equivalent. On multivariable analysis, major liver resection (OR2.70 [95%CI 1.46- 5.01], P=0.002), but not LLR (P=0.221), independently predicted major postoperative morbidity. Overall survival was similar between groups on univariable (median 47.0 vs 44.0 months, P=0.384) and multivariable analysis (P=0.152). Conclusion: LLR is feasible and safe with outcomes that are at least equivalent to open surgery. LLR may facilitate surgical resection for CRLM among patients with significant baseline comorbidity and anaesthetic risk.