Portal Vein Tumor Thrombus Research Articles

Managing hepatocellular carcinoma across the stages: efficacy and outcomes of stereotactic body radiotherapy

PurposeHepatocellular carcinoma (HCC) poses a unique challenge due to its predilection for developing on compromised livers, often limiting surgical options. Stereotactic body radiotherapy (SBRT) has emerged as a promising local treatment modality for HCC. This study aims to assess the effectiveness of SBRT in HCC patients not suitable for surgery, focusing on local control, optimal radiation dosing, and prognostic factors.MethodsIn this retrospective analysis, 52 HCC patients treated with SBRT were examined. The study assessed local control, progression-free survival (PFS), and overall survival (OS) while conducting dosimetric analyses. The relationship between mean liver dose and Child–Pugh score (CPS) progression was also explored.ResultsSBRT demonstrated 93.4% freedom from local progression (FFLP) at 12 months. Notably, a near minimum dose (D98%) below 61 Gy as an equivalent dose in 2‑Gy fractions with α/β 10 Gy (EQD2α/β10) was associated with reduced FFLP (p-value 0.034). Logistic regression analysis revealed a dose–response relationship for FFLP and D98% with 95% and 98% probability of FFLP at a dose of 56.9 and 73.1 Gy, respectively. The study observed OS rates of 63.7% at 1 year and 34.3% at 3 years. Patients with portal vein tumor thrombus (PVTT) and larger tumors (≥ 37 cm3) experienced decreased PFS and OS. Multivariate analysis identified PVTT, larger tumor volume, and performance status as independent predictors of reduced OS. Notably, classical radiation-induced disease (cRILD) was absent, but nonclassical (nc) RILD occurred in 7.7% of patients. Regression analysis linked a mean EQD2α/β3–8 dose to the liver (12.8–12.6) with a 10% likelihood of ncRILD.ConclusionSBRT offers a compelling option for achieving high local control and promising survival outcomes in HCC. The study supports a radiation dose range of 61–73.1 Gy, coupled with a mean liver dose under 12.6–12.8 Gy as EQD2, to achieve favorable FFLP rates, with acceptable toxicity rates.

Contralateral Hypertrophy Post Yttrium-90 Transarterial Radioembolization in Patients With Hepatocellular Carcinoma and Portal Vein Tumor Thrombus.

Objectives Contralateral hypertrophy of non-irradiated liver following Yttrium-90 (90Y) transarterial radioembolization (TARE) is increasingly recognized as an option to facilitate curative surgical resection in patients that would otherwise not be surgical candidates due to a small future liver remnant (FLR). This study aimed to investigate the correlation between patient features and liver hypertrophy and identify potential predictors for liver growth in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) undergoing TARE. Methodology Twenty-three patients with HCC and PVTT were included. Contralateral liver hypertrophy was assessed at six months posttreatment based on CT or MRI imaging. Thirteen patient features were selected for statistical and prediction analysis. Univariate Spearman correlation and analysis of variance (ANOVA) tests were performed. Subsequently, four feature-selection methods based on multivariate analysis were used to improve model generalization performance. The selected features were applied to train linear regression models, with fivefold cross-validation to assess the performance of the predicted models. Results The ratio of disease-free target liver volume to spared liver volume and total liver volume showed the highest correlations with contralateral hypertrophy (P-values = 0.03 and 0.05, respectively). In three out of four feature-selection methods, the feature of disease-free target liver volume to total liver volume ratio was selected, having positive correlations with the outcome and suggesting that more hypertrophy may be expected when more volume of disease-free liver is irradiated. Conclusions Contralateral hypertrophy post-90Y TARE can be an option for facilitating surgical resection in patients with otherwise small FLR.

Pre-operative enhanced magnetic resonance imaging combined with clinical features predict early recurrence of hepatocellular carcinoma after radical resection.

Indentifying predictive factors for postoperative recurrence of hepatocellular carcinoma (HCC) has great significance for patient prognosis. To explore the value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI) combined with clinical features in predicting early recurrence of HCC after resection. A total of 161 patients with pathologically confirmed HCC were enrolled. The patients were divided into early recurrence and non-early recurrence group based on the follow-up results. The clinical, laboratory, pathological results and Gd-EOB-DTPA enhanced MRI imaging features were analyzed. Of 161 patients, 73 had early recurrence and 88 were had non-early recurrence. Univariate analysis showed that patient age, gender, serum alpha-fetoprotein level, the Barcelona Clinic Liver Cancer stage, China liver cancer (CNLC) stage, microvascular invasion (MVI), pathological satellite focus, tumor size, tumor number, tumor boundary, tumor capsule, intratumoral necrosis, portal vein tumor thrombus, large vessel invasion, nonperipheral washout, peritumoral enhancement, hepatobiliary phase (HBP)/tumor signal intensity (SI)/peritumoral SI, HBP peritumoral low signal and peritumoral delay enhancement were significantly associated with early recurrence of HCC after operation. Multivariate logistic regression analysis showed that patient age, MVI, CNLC stage, tumor boundary and large vessel invasion were independent predictive factors. External data validation indicated that the area under the curve of the combined predictors was 0.861, suggesting that multivariate logistic regression was a reasonable predictive model for early recurrence of HCC. Gd-EOB-DTPA enhanced MRI combined with clinical features would help predicting the early recurrence of HCC after operation.

Evaluation of models to predict prognosis in patients with advanced hepatocellular carcinoma treated with TACE combined with apatinib.

The HAP, Six-and-Twelve, Up to Seven, and ALBI scores have been substantiated as reliable prognostic markers in patients presenting with intermediate and advanced hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) treatment. Given this premise, our research aims to assess the predictive efficacy of these models in patients with intermediate and advanced HCC receiving a combination of TACE and Apatinib. Additionally, we have conducted a meticulous comparative analysis of these four scoring systems to discern their respective predictive capacities and efficacies in combined therapy. Performing a retrospective analysis on the clinical data from 200 patients with intermediate and advanced HCC, we studied those who received TACE combined with Apatinib at the First Affiliated Hospital of the University of Science and Technology of China between June 2018 and December 2022. To identify the factors affecting survival, the study performed univariate and multivariate Cox regression analyses, with calculations of four different scores: HAP, Six-and-Twelve, Up to Seven, and ALBI. Lastly, Harrell's C-index was employed to compare the prognostic abilities of these scores. Cox proportional hazards model results revealed that the ALBI score, presence of portal vein tumor thrombus (PVTT, )and tumor size are independent determinants of prognostic survival. The Kaplan-Meier analyses showed significant differences in survival rates among patients classified by the HAP, Six-and-Twelve, Up to Seven, and ALBI scoring methods. Of the evaluated systems, the HAP scoring demonstrated greater prognostic precision, with a Harrell's C-index of 0.742, surpassing the alternative models (P < 0.05). In addition, an analysis of the area under the AU-ROC curve confirms the remarkable superiority of the HAP score in predicting short-term survival outcomes. Our study confirms the predictive value of HAP, Six-and-Twelve, Up to Seven, and ALBI scores in intermediate to advanced Hepatocellular Carcinoma (HCC) patients receiving combined Transarterial Chemoembolization (TACE) and Apatinib therapy. Notably, the HAP model excels in predicting outcomes for this specific HCC subgroup.

Adjuvant Transarterial Chemoembolization With Sorafenib for Portal Vein Tumor Thrombus

Certain patients with hepatocellular carcinoma with portal vein tumor thrombus could benefit from surgical resection, and postoperative adjuvant therapy may lower the incidence of tumor recurrence. To compare the efficacy and safety of sorafenib plus transarterial chemoembolization vs sorafenib alone as postoperative adjuvant therapy for patients with hepatocellular carcinoma with portal vein tumor thrombus. This was a phase 3, multicenter, randomized clinical trial conducted in 5 hospitals in China. A total of 158 patients were enrolled and randomized from October 2019 to March 2022, with a median follow-up of 28.4 months. Portal vein tumor thrombus was graded by the Cheng classification. Eligible patients with hepatocellular carcinoma with Cheng grade I to III portal vein tumor thrombus (ie, involving segmental or sectoral branches, right- or left-side branch, or main trunk of portal vein) were included. Patients were randomly assigned 1:1 to receive transarterial chemoembolization with sorafenib or sorafenib alone as postoperative adjuvant therapy. Sorafenib treatment was started within 3 days after randomization, with an initial dose of 400 mg orally twice a day. In the transarterial chemoembolization with sorafenib group, transarterial chemoembolization was performed 1 day after the first administration of sorafenib. The primary end point was recurrence-free survival. Efficacy was assessed in the intention-to-treat population and safety was assessed in patients who received at least 1 dose of study treatment. Of 158 patients included, the median (IQR) age was 54 (43-61) years, and 140 (88.6%) patients were male. The median (IQR) recurrence-free survival was significantly longer in the transarterial chemoembolization with sorafenib group (16.8 [12.0-NA] vs 12.6 [7.8-18.1] months; hazard ratio [HR], 0.57; 95% CI, 0.39-0.83; P = .002). The median (IQR) overall survival was also significantly longer with transarterial chemoembolization with sorafenib than with sorafenib alone (30.4 [20.6-NA] vs 22.5 [15.4-NA] months; HR, 0.57; 95% CI, 0.36-0.91; P = .02). The most common grade 3/4 adverse event was hand-foot syndrome (23 of 79 patients in the transarterial chemoembolization with sorafenib group [29.1%] vs 24 of 79 patients in the sorafenib alone group [30.4%]). There were no treatment-related deaths in either group. The transarterial chemoembolization with sorafenib group did not show additional toxicity compared with the sorafenib monotherapy group. In this study, the combination of sorafenib and transarterial chemoembolization as postoperative adjuvant therapy in patients with hepatocellular carcinoma with portal vein tumor thrombus resulted in longer recurrence-free survival and overall survival than sorafenib alone and was well tolerated. ClinicalTrials.gov Identifier: NCT04143191.

Long-term surgical outcomes of bile duct tumor thrombus versus portal vein tumor thrombus for hepatocellular carcinoma: a propensity score matching analysis.

Portal vein tumor thrombus (PVTT) seriously affects the prognosis of hepatocellular carcinoma (HCC). However, whether bile duct tumor thrombus (BDTT) significantly affects the prognosis of HCC as much as PVTT remains unclear. We aimed to compare the long-term surgical outcomes of HCC with macroscopic PVTT (macro-PVTT) and macroscopic BDTT (macro-BDTT). The data of HCC patients with macro-BDTT or macro-PVTT who underwent hemihepatectomy were retrospectively reviewed. A propensity score matching (PSM) analysis was performed to reduce the baseline imbalance. The recurrence-free survival (RFS) and overall survival (OS) rates were compared between the cohorts. Before PSM, the PVTT group had worse RFS and OS rates than the BDTT group (P = 0.043 and P = 0.008, respectively). Multivariate analyses identified PVTT (hazard ratio [HR] = 1.835, P = 0.016) and large HCC (HR = 1.553, P = 0.039) as independent risk factors for poor OS and RFS, respectively. After PSM, the PVTT group had worse RFS and OS rates than the BDTT group (P = 0.037 and P = 0.004, respectively). The 3- and 5-year OS rates were significantly higher in the BDTT group (59.5% and 52.1%, respectively) than in the PVTT group (33.3% and 20.2%, respectively). Aggressive hemihepatectomy provides an acceptable prognosis for HCC patients with macro-BDTT. Furthermore, the long-term surgical outcomes of HCC patients with macro-BDTT were significantly better than those of HCC patients with macro-PVTT.

Identification of key molecules in the formation of portal vein tumor thrombus in hepatocellular carcinoma based on single cell transcriptomics and in vitro experiments.

The presence of portal vein tumor thrombus (PVTT) is a significant indicator of advanced-stage hepatocellular carcinoma (HCC). Unfortunately, the prediction of PVTT occurrence remains challenging, and there is a lack of comprehensive research exploring the underlying mechanisms of PVTT formation and its association with immune infiltration. Our approach involved analyzing single-cell sequencing data, applying high dimensional weighted gene co-expression network analysis (hdWGCNA), and identifying key genes associated with PVTT development. Furthermore, we constructed competing endogenous RNA (ceRNA) networks and employed weighted gene co-expression network analysis (WGCNA), as well as three machine-learning techniques, to identify the upstream regulatory microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) of the crucial mRNAs. We employed fuzzy clustering of time series gene expression data (Mfuzz), gene set variation analysis (GSVA), and cell communication analysis to uncover significant signaling pathways involved in the activation of these important mRNAs during PVTT development. In addition, we conducted immune infiltration analysis, survival typing, and drug sensitivity analysis using The Cancer Genome Atlas (TCGA) cohort to gain insights into the two patient groups under study. Through the implementation of hdWGCNA, we identified 110 genes that was closely associated with PVTT. Among these genes, TMEM165 emerged as a crucial candidate, and we further investigated its significance using COX regression analysis. Furthermore, through machine learning techniques and survival analysis, we successfully identified the upstream regulatory miRNA (hsa-miR-148a) and lncRNA (LINC00909) that targeted TMEM165. These findings shed light on the complex regulatory network surrounding TMEM165 in the context of PVTT. Moreover, we conducted CIBERSORT analysis, which unveiled correlations between TMEM165 and immune infiltration in HCC patients. Specifically, TMEM165 exhibited associations with various immune cell populations, including memory B cells and CD8+ T cells. Additionally, we observed implications for immune function, particularly in relation to immune checkpoints, within the context of HCC. The regulatory axis involving TMEM165, hsa-miR-148a, and LINC00909 emerges as a crucial determinant in the development of PVTT in HCC patients, and it holds significant implications for prognosis. Furthermore, alterations in the TMEM165/hsa-miR-148a/LINC00909 regulatory axis exhibit a strong correlation with immune infiltration within the HCC tumor microenvironment, leading to immune dysfunction and potential failure of immunotherapy.

Co-relation of Portal Vein Tumour Thrombus Response With Survival Function Following Robotic Radiosurgery in Vascular Invasive Hepatocellular Carcinoma

Purpose or ObjectiveProspective evaluation of stereotactic body radiotherapy (SBRT) with Robotic Radiosurgery in hepatocellular carcinoma patients with macrovascular invasion (HCC-PVT). Materials and MethodsPatients with inoperable HCC-PVT, good performance score (PS0-1) and preserved liver function (up to Child Pugh B7) were accrued after ethical and scientific committee approval [CTRI: 2022/01/050234] for treatment on Robotic Radiosurgery (M6) and planned with Multiplan (iDMS V2.0). Triple-phase contrast computed tomography (CT) scan was done for contouring and gross tumor volume (GTV) included contrast enhancing mass within main portal vein and adjacent parenchymal disease. Dose prescription was as per risk stratification protocol (22- 50Gy in 5 fractions) while achieving the constraints of mean liver dose <15Gy, 800 cc liver <8Gy and the duodenum max of <24 Gy). Response assessment done at 2 months follow up for recanalization. Patient and treatment related factors evaluated for influence in survival function. ResultsBetween Jan 2017 till May 2022, 317 consecutive HCC with PVT patients were screened and 219 patients were accrued [male 92%, CP score 5-7 90%, mean age 63 years (38-85yrs), CLIP <3: 84 (40%), 3-6 117 (56%), infective etiology 9.5%, Performance status (PS) 0-37%; 1-56%]. Among 209 consecutive patients after accrual SBRT treatment done (10 patients were excluded after accrual due to ascites and decompensation), 139 were evaluable for response assessment (>2 mo follow up). At mean follow up of 10.2 months (SD 8.43), 88 (63%) patients expired and 51 (36%) were alive. 82 (59%) patients had recanalization of PVT (response), 57 (41%) pts did not recanalize, 28 (17%) had progressive disease had progressive/metastatic disease prior to response evaluation (<2 months). Mean overall survival in responders and non-responders were 18.4 (SE 2.52) and 9.34 month (SE 0.81) respectively (p<0.001). Mean survival in patients with PS0, PS1 and PS2 were 17, 11.7 and 9.7 months (p- 0.019) respectively. Overall survival (OS) in partial recanalization, bland thrombus and complete recanalization was 12.4, 14.1, 30.3 months respectively (p-0.002). Adjuvant sorafenib, Barcelona Clinic Liver Classification (BCLC) stage, gender, age, RT dose did not influence response to treatment. Recanalization rate was higher in good PS patients (p-0.019). OS in patients with response to treatment, no response to treatment, fit but not accrued and not suitable patients were 18.4, 9.34, 5.9, 2.6 months respectively (p-<0.001). 36/139 patients (24%) had RILD [10 (7.2%) had Classic Radiation induced liver disease (RILD) & 26 (19%) had non-classic RILD]. Derangement in Child Pugh Score (CP score change) by more than 2 was seen in 30 (24%) within 2-month period after Robotic Radiosurgery. 18 (13%) had unplanned admissions, two patients required embolization due to fiducial related bleeding, 20 (14%) had ascites of which 9 (6%) patients required abdominocentesis. ConclusionPVT response or recanalization after SBRT is a statistically significant prognostic factor for survival function in HCC-PVT.

HCC portal hypertension imaging score derived from CT predicts re-bleeding and mortality after acute variceal bleeding

Background/PurposeRisk factors for re-bleeding and death after acute variceal bleeding (AVB) in cirrhotic HCC patients are not fully understood.We aimed to (1) explore how the combination of high-risk esophageal varices, HCC status, and portal vein tumor thrombus (i.e., HCC Portal Hypertension Imaging Score [HCCPHTIS]) helps predict increased risk of variceal re-bleeding and mortality; (2) assess predictability and reproducibility of the identified variceal re-bleeding rules.MethodsThis prospective study included 195 HCC patients with first-time AVB and liver cirrhosis, and conducted multivariable Cox regression analysis and Kaplan-Meier analysis. Receiver operating characteristic curve analysis was calculated to find the optimal sensitivity, specificity, and cutoff values of the variables. The reproducibility of the results obtained was verified in a different but related group of patients.Results56 patients (28.7%) had re-bleeding within 6 weeks; HCCPHTIS was an independent risk factor for variceal re-bleeding after AVB (Odd ratio, 2.330; 95% confidence interval: 1.728–3.142, p < 0.001). The positive predictive value of HCCPHTIS cut off value > 3 was 66.2%, sensitivity 83.9%, and specificity 82.3%. HCCPHTIS area under the curve was higher than Child-Pugh score (89% vs. 75%, p < 0.001). 74(37.9%) death occurred within 6 weeks; HCCPHTIS > 4 was associated with increased risk of death within 6 weeks after AVB (p < 0.001).ConclusionHCCPHTIS > 3 is a strong predictor of variceal re-bleeding within the first 6 weeks. However, patients with HCCPHTIS > 4 were at increased risk of death within 6 weeks.

Transarterial chemoembolization with molecular targeted therapies plus camrelizumab for recurrent hepatocellular carcinoma

BackgroundThe safety and efficacy of transarterial chemoembolization plus molecular targeted therapy (MTT) combined with immune checkpoint inhibitors (ICIs) in primary liver cancer have been demonstrated. However, the evidence for TACE plus MTT combined with ICIs in the treatment of recurrent hepatocellular carcinoma (RHCC) is limited. Given the excellent performance of this combination regimen in primary liver cancer, it is necessary to evaluate the efficacy of TACE plus MTT combined with ICIs in RHCC.MethodsA total of 88 patients with RHCC treated with TACE plus MTT combined with camrelizumab (TACE-TC group, n = 46) or TACE plus MTT (TACE-T group, n = 42) were retrospectively collected and analyzed. In this study, we evaluated the effectiveness and safety of combination therapy for patients with RHCC by analyzing tumor response, progression-free survival (PFS), overall survival (OS), laboratory biochemical indices, and adverse events (AEs).ResultsTACE-TC was superior to TACE-T in PFS (14.0 vs. 8.9 months, p = 0.034) and OS (31.1 vs. 20.2 months, p = 0.009). Moreover, TACE-TC achieved more preferable benefits with respect to disease control rate (89.1% vs. 71.4%, p = 0.036) and objective response rate (47.8% vs. 26.2%, p = 0.036) compared with TACE-T in patients with RHCC. Compared with the TACE-T group, the AFP level in the TACE-TC group decreased more significantly after 3 months of treatment. Multivariate analysis showed that treatment option was a significant predictor of OS and PFS, while the portal vein tumor thrombus and interval of recurrence from initial treatment were another prognostic factor of PFS. There was no significant difference between the TACE-TC and TACE-T groups for Grade 3–4 adverse events.ConclusionsA combination therapy of TACE, MTT, and camrelizumab significantly improved tumor response and prolonged survival duration, showing a better survival prognosis for RHCC patients.

Salvage Surgery for Initially Unresectable HCC With PVTT Converted by Locoregional Treatment Plus Tyrosine Kinase Inhibitor and Anti-PD-1 Antibody.

This study aimed to compare the survival outcomes of patients with initially unresectable hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) who underwent or did not undergo salvage surgery followed by a triple combination conversion treatment consisted of locoregional treatment (LRT), tyrosine kinase inhibitors (TKIs), and anti-PD-1 antibodies. The data from 93 consecutive patients with initially unresectable HCC and PVTT across 4 medical centers were retrospectively reviewed. They were converted successfully by the triple combination treatment and underwent or did not undergo salvage resection. The baseline characteristics, conversion schemes, conversion treatment-related adverse events (CTRAEs), overall survival (OS), and progression-free survival (PFS) of the salvage surgery and non-surgery groups were compared. Multivariate Cox regression analysis was performed to identify independent risk factors for OS and PFS. Additionally, subgroup survival analysis was conducted by stratification of degree of tumor response and type of PVTT. Of the 93 patients, 44 underwent salvage surgery, and 49 did not undergo salvage surgery. The OS and PFS of the salvage surgery and non-surgery groups were not significantly different (P = .370 and .334, respectively). The incidence and severity of CTRAEs of the 2 groups were also comparable. Subgroup analyses revealed that for patients with complete response (CR) or types III-IV PVTT, there was a trend toward better survival in patients who did not undergo salvage surgery. Multivariate analysis showed that baseline α-fetoprotein and best tumor response per mRECIST criteria were independent prognostic factors for OS and PFS. For patients with initially unresectable HCC and PVTT who were successfully converted by the triple combination therapy, salvage liver resection may not be necessary, especially for the patients with CR or types III-IV PVTT.

Novel concept of "sequential particle radiotherapy" with atezolizumab plus bevacizumab for hepatocellular carcinoma with portal vein tumor thrombus.

Owing to the high objective response rate of atezolizumab plus bevacizumab (Atez/Bev) for hepatocellular carcinoma (HCC), the concept of sequential conversion to local treatment has recently become mainstream. The conversion concept is mainly applied to Barcelona Clinic for Liver Cancer (BCLC) stage B cases, and radiotherapy is rarely considered as a conversion local treatment. We herein report three patients who were treated with the novel concept of "sequential particle radiotherapy," consisting of Atez/Bev therapy followed by particle radiotherapy (PRT) for HCC with advanced portal vein tumor thrombus (Vp3/4 PVTT). All patients achieved partial response radiologically and were switched to PRT. All patients were recurrence free at 1year after the introduction of Atez/Bev therapy without any additional treatment. This upcoming combination strategy includes the advocacy of sequential concepts for BCLC stage C cases and the introduction of PRT as a local treatment after Atez/Bev.

Prognostic Evaluation for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus Patients Treated with Transarterial Chemoembolization Plus Molecular Targeted Therapies—Development and Validation of the ABPS Score

Rationale and objectivesTransarterial chemoembolization (TACE) plus molecular targeted therapies has emerged as the main approach for treating hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). A robust model for outcome prediction and risk stratification of recommended TACE plus molecular targeted therapies candidates is lacking. We aimed to develop an easy-to-use tool specifically for these patients. MethodsA retrospective analysis was conducted on 384 patients with HCC and PVTT who underwent TACE plus molecular targeted therapies at 16 different institutions. We developed and validated a new prognostic score which called ABPS score.Additionally, an external validation was performed on data from 200 patients enrolled in a prospective cohort study. ResultsThe ABPS score (ranging from 0 to 3 scores), which involves only Albumin-bilirubin (ALBI, grade 1：0 score；grade 2：1 score), PVTT(I-II type：0 score；III-IV type：1 score), and systemic-immune inflammation index (SII,<550×1012：0 score；≥550×1012：1 score). Patients were categorized into three risk groups based on their ABPS score: ABPS-A, B, and C (scored 0, 1-2, and 3, respectively). The concordance index (C-index) of the ABPS scoring system was calculated to be 0.802, significantly outperforming the HAP score (0.758), 6-12 (0.712), Up to 7 (0.683), and ALBI (0.595) scoring systems (all P< 0.05). These research findings were further validated in the external validation cohorts. ConclusionsThe ABPS score demonstrated a strong association with survival outcomes and radiological response in patients undergoing TACE plus molecular targeted therapy for HCC with PVTT. The ABPS scoring system could serve as a valuable tool to guide treatment selection for these patients.

Efficacy and Safety of Drug-Loaded Microsphere-Based Transcatheter Arterial Chemoembolization for the Treatment of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus

In this study, we evaluate the effectiveness and safety of conventional transcatheter arterial chemoembolization (C-TACE) and drug-loaded microsphere-based TACE (DEB-TACE) in patients with hepatocellular carcinoma (HCC) accompanied by portal vein tumor thrombus (PVTT). A total of 51 HCC patients with PVTT treated at our hospital between August 2016 and December 2021 were collected and retrospectively analyzed. 39 patients were in the DEB-TACE group and 9 patients were in the C-TACE group, after excluding 3 patients. Serum alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) levels were assessed using magnetic nanoparticle-based chemiluminescence immunoassay. The liver function was evaluated before TACE, at 1 month, and at 3 months after treatment. The therapeutic response and intraoperative and postoperative adverse events were analyzed in two groups. Both TACE treatments effectively reduced tumor thrombus size, tumor count, and PVTT classification, with DEB-TACE demonstrating superior efficacy. The median survival time was slightly longer in the DEB-TACE group (14 months) compared to the c-TACE group (11 months), but there were no significant differences in the survival curves. Both groups experienced decreased postoperative AFP levels, while PIVKA-II levels remained stable without significant differences between the two groups. The PIVKA-II index exhibited no significant alteration, and there was no notable disparity observed between the two groups. There were no statistically significant differences observed in liver function and postoperative adverse reactions between the two groups after the operation. In conclusion, the therapeutic effect and safety of DEB-TACE are found to be equivalent to those of C-TACE.

Transcatheter arterial chemoembolization combined with PD-1 inhibitors and Lenvatinib for hepatocellular carcinoma with portal vein tumor thrombus.

Hepatocellular carcinoma (HCC) patients complicated with portal vein tumor thrombus (PVTT) exhibit poor prognoses and treatment responses. To investigate efficacies and safety of the combination of PD-1 inhibitor, transcatheter arterial chemoembolization (TACE) and Lenvatinib in HCC subjects comorbid with PVTT. From January 2019 to December 2020, HCC patients with PVTT types I-IV were retrospectively enrolled at Beijing Ditan Hospital. They were distributed to either the PTL or TACE/Lenvatinib (TL) group. The median progression-free survival (mPFS) was set as the primary endpoint, while parameters like median overall survival, objective response rate, disease control rate (DCR), and toxicity level served as secondary endpoints. Forty-one eligible patients were finally recruited for this study and divided into the PTL (n = 18) and TL (n = 23) groups. For a median follow-up of 21.8 months, the DCRs were 88.9% and 60.9% in the PTL and TL groups (P = 0.046), res-pectively. Moreover, mPFS indicated significant improvement (HR = 0.25; P < 0.001) in PTL-treated patients (5.4 months) compared to TL-treated (2.7 months) patients. There were no treatment-related deaths or differences in adverse events in either group. A triplet regimen of PTL was safe and well-tolerated as well as exhibited favorable efficacy over the TL regimen for advanced-stage HCC patients with PVTT types I-IV.

Sintilimab plus bevacizumab combined with radiotherapy as first-line treatment for hepatocellular carcinoma with portal vein tumor thrombus: A multicenter, single-arm, phase 2 study.

Systemic treatments are listed as first-line therapies for HCC with portal vein tumor thrombus (PVTT), resulting in modest efficacy. We aimed to evaluate the efficacy and safety of sintilimab plus bevacizumab combined with radiotherapy in HCC with PVTT and to identify prognostic biomarkers. This open-label, multicenter, single-arm, phase 2 clinical trial was conducted at 3 tertiary hospitals in China. A total of 46 patients with HCC with PVTT were enrolled. All the patients received the first cycle of i.v. sintilimab (200mg, day 1) plus bevacizumab (15mg/kg, day 1) within 3 days after enrollment. Radiotherapy (30-50Gy/10 fractions) was administered after 2 cycles of Sin-Bev. Sin-Bev was disrupted during radiotherapy and resumed 2 weeks after radiotherapy and continued every 3 weeks thereafter until disease progression, unacceptable toxicity, or withdrawal of consent. The primary end point was objective response rate. Patients obtained an objective response rate of 58.7% and a disease control rate of 100%. After a median follow-up time of 26.0 months (95% CI: 24.0-26.0), the median OS was 24.0 months (95% CI: 19.0 to not applicable) and the median progression-free survival was 13.8 months (95% CI: 12.0-21.0), respectively. No unexpected adverse events or treatment-related deaths occurred. Mutations of PCTMD1 were predictive of shorter OS and progression-free survival. Sintilimab plus bevacizumab combined with radiotherapy provides favorable treatment response and survival outcomes along with an acceptable safety profile in the first-line setting for patients with HCC with PVTT (ClinicalTrials.gov Identifier: NCT05010434).

Efficacy of radiotherapy in combined treatment of hepatocellular carcinoma patients with portal vein tumor thrombus: a real-world study

Background and aimsHepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) has an extremely poor prognosis. A previous study proved that low-dose radiotherapy (RT) could prolong the prognosis of HCC patients with PVTT. This study aims to explore the sensitivity of PVTT to RT treatment.MethodsPatients were selected based on imaging diagnosis of HCC accompanied by PVTT and received combined treatment of radiotherapy, antiangiogenic drugs and immune checkpoint inhibitors, followed by hepatectomy or liver transplantation from January 2019 to August 2022. The efficacy was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines and pathological assessment. The sensitivity of tumor cells to the treatment was compared between the primary tumor (PT)and PVTT by analyzing their residual tumor and pathologic complete remission (PCR) incidence.ResultsData from 14 patients were collected in the study. After combined treatment, the size of PVTT decreased more significantly than that of the primary tumor in the imaging study (p < 0.05). The residual cancer was significantly more restrictive than that of primary tumor in paired patients based on pathological measurement (p = 0.008). The PCR incidence of the primary tumor (21.42%) was significantly lower (p = 0.008) than that of PVTT in the pathologic study (78.57%).ConclusionPVTT is more sensitive to radiotherapy treatment than the primary tumor in patients with HCC. This combination therapy might be an effective option as a downstaging therapy for patients with HCC with PVTT.

Treatment of hepatocellular carcinoma with a portal vein tumor thrombus and pulmonary metastases of rectal cancer with microsatellite stability using atezolizumab plus bevacizumab.

Herein, we report the successful treatment using atezolizumab plus bevacizumab of a patient with hepatocellular carcinoma (HCC) with a portal vein tumor thrombus and multiple pulmonary metastases from rectal cancer with microsatellite stability. This patient developed rectal cancer with synchronous pulmonary metastases and HCC. After resecting the primary lesion of the rectal cancer, transcatheter arterial chemoembolization was performed for the HCC. Drug therapy was planned for multiple pulmonary metastases of rectal cancer; however, the early development of recurrent HCC with portal vein tumor thrombus had to be highly prioritized, and atezolizumab plus bevacizumab was introduced. Following the disappearance of the recurrent HCC lesion, the metastatic pulmonary nodules shrunk into scar-like spots. The treatment for both HCC and pulmonary metastases of rectal cancer were considered to result in clinical complete response.

The influencing factors for tumor thrombus in patients with hepatocellular carcinoma.

Microvascular invasion (MVI) is considered to be an important factor in the early invasion and metastasis of liver cancer, and the survival rate of patients with MVI is much lower than that of patients without MVI. Therefore, it is crucial to accurately predict the independent predictors of tumor thrombus formation. This study aimed to assess the risk factors for tumor thrombus grades in patients with hepatocellular carcinoma (HCC). Between August 2011 and December 2022, the data of 231 patients diagnosed with HCC were collected and divided into the following three groups: an MVI-negative group, an MVI-positive group, and a portal vein tumor thrombus (PVTT) group. Univariate analysis was used to compare the differences between the three groups in terms of clinical features, pathology, and imaging features. Multiple logistic regression analysis was used to analyze the risk factors associated with tumor thrombus grades, and the cutoff value was finally calculated by using the receiver operating characteristic (ROC) curve. The incidence of MVI and PVTT in the patients with HCC were 10.0% and 6.1%, respectively; univariate analysis revealed statistically significant differences in tumor diameter, alpha fetoprotein level, Ki-67 expression level, gender, tumor quantity, arteriovenous fistula, peritumoral enhancement, and satellite nodules among the three groups (P<0.05). Multiple logistic regression analysis showed that Ki-67 expression level, tumor diameter, and peritumoral enhancement were independent risk factors for tumor thrombus grades (P<0.05). The area under the curve (AUC) of Ki-67 expression level and tumor diameter was 0.713 [95% confidence interval (CI): 0.626-0.800] and 0.753 (95% CI: 0.669-0.837), respectively, and the AUC of the combination analysis was 0.805 (95% CI: 0.723-0.888), with a cutoff value of 17.5% and 4.1 cm, respectively (P<0.05). Tumor diameter, Ki-67 expression level, and peritumoral enhancement can be used as independent predictors of tumor thrombus in patients with HCC. The combination of tumor diameter and Ki-67 expression level can further improve diagnostic efficacy.

Preliminary results of ALTER-H006: A phase II study of TQB2450 plus anlotinib as adjuvant therapy in hepatocellular carcinoma (HCC) with high risk of recurrence after radical resection.

494 Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death. Surgical resection remains as the mainstay of curative treatment option, However, the recurrence rate after surgical resection could be high especially in patients with CNLC stage IIb (tumor number ≥ 4) and IIIa (vascular invasion). Herein we evaluated the efficacy and safety of the anti-angiogenic tyrosine kinase inhibitor, anlotinib, plus TQB2450, a novel programmed death-ligand 1 (PD-L1) inhibitor as an adjuvant treatment for HCC with high risk of recurrence after radical resection. Methods: This prospective, multiple-center, single-arm phase II study (NCT05111366) enrolled histologically confirmed resectable HCC pts for CNLC Stage IIb/IIIa with any of the following high-risk factors for recurrence: a) tumor nodules ≥4; b) portal vein tumor thrombus (PVTT): vp1 or vp2; c) hepatic vein tumor thrombus (HVTT): vv1 or vv2. At 4-8 weeks after R0 resection, adjuvant therapy was started with anlotinib (12 mg, p.o., qd, d1-14, q3w) plus TQB2450 (1200 mg, i.v., d1, q3w) until disease recurrence or unacceptable toxicity or up to 18 cycles (~1 year). Primary endpoint was 1-year recurrence-free survival (RFS) rate; secondary endpoints were RFS, 1-year overall survival (OS) rate, and safety. Results: Between January 2022 and August 2023, a total of 22 pts from 4 centers were enrolled, 21 pts included in per-protocol set analysis. The 21 pts were predominantly male (95 %, n = 20), and the median age was 50 years (range: 33–75). Eight pts (38%) had CNLC Stage IIb and 13(62%) had CNLC Stage IIIa HCC. Among them, 19 pts received at least once tumor assessment. According to RECIST 1.1, out of 21 pts, 16 showed no recurrence, 3 relapsed, 1 dropped out and 1 discontinued due to serious adverse events. The 1-year RFS rate was 62.31%（95%CI: 17.15-88.08）, while the median RFS was not mature. Additionally, safety profile exhibited that the regimen was tolerable. 16 of 22 pts (73%) experienced treatment-related adverse events (TRAEs). Grade 3 TRAEs occurred in 6 pts (27 %) including hypertension (13.5 %), neutropenia (9 %), and bleeding (4.5 %). Conclusions: The present study indicated that anlotinib plus TQB2450 as adjuvant treatment for HCC with high risk of recurrence after radical resection exhibited potential efficacy and tolerable safety profile. The conclusion should be validated in more participants included subsequently. Clinical trial information: NCT05111366 .