Tumor Thrombosis Research Articles

Portal Venous Tumor Thrombosis and Visceral Organ Metastasis without Skeletal Involvement in mCRPC: Adverse Prognostic Indicators on Dual Tracer PET/CT and Clinical Outcome after 177Lu-PSMA-617 PRLT and Cabazitaxel Therapy

AbstractProstate cancer involving visceral organs are occurrences in the later disease course, usually following regional nodal and skeletal involvement, and are refractory to conventional treatment. A 61-year-old male patient presented with locally advanced disease at presentation, which progressed on androgen deprivation therapy and systemic therapy with involvement of the visceral organs (lungs and liver). Portal venous tumor thrombosis involving the right and main branch was also observed on contrast-enhanced computed tomography (CECT) and magnetic resonance imaging (MRI), which showed intense uptake on 68Ga-labeled prostate-specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA-11 PET/CT) and 18F-fluorodeoxyglucose PET/CT (18F-FDG-PET/CT). Post-177Lu-PSMA-617 radioligand therapy (PRLT) showed mixed response on tumor marker and imaging analysis with survival of 6 months after 177Lu-PSMA radioligand therapy. The high Gleason score, visceral organ metastasis, and increased metabolic activity on FDG were the adverse prognostic factors in the described patient.

Efficacy and safety of hepatic arterial infusion chemotherapy combined with tyrosine kinase inhibitors and immune checkpoint inhibitors in the treatment of advanced hepatocellular carcinoma with portal vein tumor thrombosis in the main trunk.

To evaluate the efficacy and safety of mFOLFOX-based hepatic arterial infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) in the treatment of advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). This retrospective study included patients who received mFOLFOX-based HAIC combined with TKIs and ICIs from January 2021 to January 2023. The primary outcome was the objective response rate of PVTT response, and the secondary outcomes were 6-month, 1-year survival rate, overall survival (OS), and corresponding adverse events and complications were also evaluated. PVTT responses were assessed using ITK-SNAP software. A total of 37 patients were included in the analysis, 18.92% achieved a complete response and 56.76% achieved a partial response in PVTT response. The objective response rate (ORR) of PVTT was 75.68%. The 6-month survival rate was 89%, the 1-year survival rate was 66%, and the median OS was 15.8 months. In univariate analysis, Child-Pugh score (P=0.010) was important factor for predicting OS; in multivariate analysis, Child-Pugh score (P=0.015, HR= 3.089, 95%CI: 1.250-7.633) was the important factor for predicting OS. In terms of adverse reactions, the most common adverse reactions associated with HAIC are pain and thrombocytopenia associated with oxaliplatin. FOLFOX-based HAIC combined with TKIs and ICIs induced an objective response rate of 75.68% in PVTT. FOLFOX-based HAIC combined with TKIs and ICIs provides more treatment options for PVTT.

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.

Epidemiology of clinically unsuspected venous thromboembolism in children with cancer: A population-based study from Maritimes, Canada.

Inconsistencies in the definition of clinically unsuspected venous thromboembolism (VTE) in pediatric patients recently led to the recommendation of standardizing this terminology. Clinically unsuspected VTE (cuVTE) is defined as the presence of VTE on diagnostic imaging performed for indications unrelated to VTE in a patient without symptoms or clinical history of VTE. The prevalence of cuVTE in pediatric cancer patients is unclear. Therefore, the main objective of our study was to determine the prevalence of cuVTE in pediatric cancer patients. All patients 0-18years old, treated at the IWK in Halifax, Nova Scotia, from August 2005 through December 2019 with a known cancer diagnosis and at least one imaging study were eligible (n=743). All radiology reports available for these patients were reviewed (n=18,120). The VTE event was labeled a priori as cuVTE event for radiology reports that included descriptive texts indicating a diagnosis of thrombosis including thrombus, central venous catheter-related, thrombosed aneurysm, tumor thrombosis, non-occlusive thrombus, intraluminal filling defect, or small fragment clot for patients without documentation of clinical history and or signs of VTE. A total of 18,120 radiology reports were included in the review. The prevalence of cuVTE was 5.5% (41/743). Echocardiography and computed tomography had the highest rate of cuVTE detection, and the most common terminologies used to diagnose cuVTE were thrombus and non-occlusive thrombus. The diagnosis of cuVTE was not associated with age, sex, and type of cancer. Future efforts should focus on streamlining radiology reports to characterize thrombi. The clinical significance of these cuVTE findings and their application to management, post-thrombotic syndrome, and survival compared to cases with symptomatic VTE and patients without VTE should be further studied.

Multidisciplinary treatment for patients with advanced hepatocellular carcinoma complicated by Vp4 portal vein tumor thrombosis: Combination of atezolizumab and bevacizumab after hepatic arterial infusion chemotherapy and radiotherapy: A case series

Rationale: Various treatments are available for treating hepatocellular carcinoma (HCC). Among HCC, Vp4 portal vein tumor thrombosis (PVTT) has a poor prognosis. There have been reports of treatment with molecularly targeted agents in combination with hepatic arterial infusion chemotherapy (HAIC) and radiotherapy (RT) in HCC patients with Vp4 PVTT, but none with atezolizumab, the immune checkpoint inhibitor. Here, we present cases of unresectable HCC with Vp4 PVTT that were treated with the combination atezolizumab and bevacizumab (Atezo + Bev) after HAIC and RT. The purpose and significance of this study are to research the usefulness to precede HAIC and RT in the treatment of HCC with immune checkpoint inhibitors. Patient concerns: Sixty-six-year-old man, 74-year-old man, 83-year-old man, 69-year-old man, 62-year-old man, and 85-year-old woman were diagnosed with HCC with Vp4 PVTT. Diagnosis: Cirrhosis was classified as Child-Pugh class A or B. HCC was diagnosed as TNM stage IVa or IVb. Interventions: RT for PVTT was performed the same day or the day after HAIC. Atezo + Bev was started at least 1 week after RT was completed. Outcomes: Death was confirmed in 4 of the 6 patients; the median overall survival time was not reached. The survival times of the 4 patients were 18.7, 12.5, 5.1, and 1.7 months. Based on the modified response evaluation criteria in solid tumors criteria, the objective response rate of patients with best tumor response to Atezo + Bev therapy was 66.7%, and that of patients with best response of PVVT to Atezo + Bev was 66.7%. Lessons: These cases showed that in HCC with Vp4 PVTT, HAIC, and RT before Atezo + Bev may be useful to prolong survival.

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.

Phase I/II first-in-human study to evaluate the safety and efficacy of tissue factor-ADC MRG004A in patients with solid tumors.

3002 Background: Tissue factor (TF) overexpression is associated with thrombosis, metastasis and poor prognosis in solid tumors, including cervical and pancreatic cancer. MRG004A is a novel anti-TF monoclonal antibody conjugated (ADC) to MMAE payload (drug-to-antibody ratio: 3.8), utilizing Glycoconnect site-specific conjugation technology. Herein, we present the preliminary safety and efficacy data from phase I/II MRG004A-001. Methods: This is an interim report (Data cutoff: Dec 15, 2023) of first-in-human, dose-escalation and expansion study ongoing in the USA and China. Pts with ECOG 0-1 with unresectable/metastatic solid tumor with measurable disease per RECIST v1.1 that progressed on prior systemic therapy, received MRG004A monotherapy Q3W intravenously. The primary objectives were to assess the safety, activity, maximal tolerated dose (MTD) and recommended phase 2 dose (RP2D). Baseline tissue was evaluated for the association of TF expression with objective response rate (ORR) and disease control rate (DCR). Results: Sixty-three pts were enrolled with 43 in dose-escalation phase (8 dose levels [0.3-2.6mg/kg]) and 20 in dose-expansion phase (15 at 2.0mg/kg and 5 at 2.4mg/kg). Median age 58 (38-75). ECOG0: 8 (13%) pts. Female: 37 (59%) pts. Median 3 prior lines of therapy: 3 (1-10). MTD was not reached. Sixteen baseline samples were evaluated for overall % membrane positivity by immunohistochemistry. Nineteen were pancreatic cancer (PC) and 68% (13/19) had TF ≥50% and 2 or 3 (+). Five received dose &lt;2 mg/kg Q3W. Significant anti-tumor activity of MRG004A was observed in pts with PC. Among 12 evaluable pts with PC in the 2.0mg/kg cohort, who have received median 3 lines of prior therapy, there were 4 PR and 6 SD. ORR was 33.3% (4/12) and DCR was 83.3% (10/12). Among them, 5 pts with PC of TF expression ≥50% and 3+ intensity and ≤2 prior lines of therapy received MRG004A at 2mg/kg. 4 of 5 TF-overexpressed PC achieved PR and 1 SD. Also, MRG004A showed efficacy in other cancers. In 4 pts with heavily-treated triple-negative breast cancer (TNBC), ORR and DCR were 25% (1/4) and 50% (2/4), respectively. In 2 pts with cervical cancer with four prior therapy lines, 1 PR and 1 SD. Common treatment-related adverse events (TRAE) of any grade include conjunctivitis (27%), anemia (17%), and hypoalbuminemia (13%) and 7.9% (5/63) pts had serious adverse events. One pt with TNBC treated at 1.8mg/kg experienced G3 Steven Johnson Syndrome, a dose-limiting toxicity (DLT), but resolved. No other DLT was observed and dose expansion and matured outcome evaluation is ongoing. Conclusions: MRG004A demonstrated a manageable toxicity and a striking antitumor activity across multiple tumor types with high TF expression in heavily pretreated setting, including pancreatic cancers. These encouraging findings warrant further evaluation of MRG004A, particularly in the context of TF-overexpressed solid tumors. Clinical trial information: NCT03941574 .

A comprehensive analysis of portal vein thrombosis in malignancy.

e24042 Background: Portal vein thrombosis (PVT) is a rare venous thromboembolism, is often linked to cirrhosis, infection, and malignancy. Advancements in imaging have noted an increasing incidence of PVT, particularly in solid cancers. Treating PVT with malignancy is challenging due to lack of data, poor recanalization, and substantial bleeding risk with anticoagulation. This study aims to enhance understanding of malignancy-related PVT, anticoagulation trends, and assess prognosis. Methods: We conducted a multicenter, observational retrospective analysis of patients diagnosed with PVT (ICD code 452,181) from 2013 to 2023. Inclusion criteria: age &gt; 18 and acute portal vein thrombosis. Exclusion criteria: presence of tumor thrombosis, and thrombus in other splanchnic vessels (e.g., mesenteric vein). Data entry was performed on a study-specific REDCap database. Patients with concomitant malignancy were identified and further assessed for cancer type, anticoagulation use, bleeding outcomes, and prognosis. Proportion analysis using Z test was done to compare outcomes between groups. Results: In our study of 583 patients, 236 (40.48%) had concurrent malignancy, predominantly male (144, 61.01%),and female (92, 38.98%) mean age 65. Common malignancies included HCC (28.38%), pancreatic (24.15%), colo-rectal (11.86%), cholangiocarcinoma (8.47%), myeloproliferative neoplasm, prostate, and gynecological cancers each (2.96%), and other cancers (18.22%). 41% had metastasis to liver. Cirrhosis was present in 40%, particularly in HCC patients (89%). Of the total,163 (69%) received anticoagulation; 26.38% showed improvement or re-canalization within a year. The primary anticoagulants were Direct Oral Anticoagulants (DOACs) (57%), with an increasing trend in the last 5 years (69.44%), followed by Low-Molecular-Weight Heparin (LMWH) (19%) and warfarin (14%). Most patients initiated on heparin infusion (9.81%) transitioned to hospice care. Bleeding events in patients receiving DOAC versus LMWH + Warfarin were 36.55% and 33.33%, respectively (p = 0.69). Patients without anticoagulation demonstrated a higher one-year mortality compared to those with anticoagulation (83.56% vs. 63.19%, p value &lt; 0.05). Overall,malignancy-associated PVT had a significantly higher case fatality rate than non-malignancy cases, regardless of anticoagulation (81.35% vs. 32.85%, p &lt; 0.05). Conclusions: There is a significant association between malignancy and PVT, particularly in HCC and pancreatic cancer. The increased mortality in malignancy-related PVT emphasizes the critical role of anticoagulation, which has demonstrated efficacy in improving outcomes, including one-year mortality. Although DOACs have seen increased use in the last 5 years, bleeding events have remained comparable. Further research is warranted to explore patient selection for optimal anticoagulation strategies.

Liver transplantation for advanced hepatocellular carcinoma: Controversy over portal vein tumor thrombosis

Liver transplantation (LT) is considered the ideal treatment for hepatocellular carcinoma (HCC) concurrent with underlying cirrhotic liver disease. As well-known, LT for HCC based on the Milan criteria has shown satisfactory outcomes. However, numerous expanded transplantation criteria were proposed to benefit more patients for LT and showed comparable survivals as well. In addition, a modest expansion of transplantation criteria for HCC may be acceptable on the basis of the consensus within the transplantation community. Nonetheless, LT in patients with advanced HCC and portal vein tumor thrombosis (PVTT) recently has received attention and has been reported by many transplantation centers despite being contraindicated. Of those, the LT outcomes in certain HCC patients with PVTT were favorable. Additionally, the advancement of multimodality treatments and the evolution of systemic therapies have emerged as promising therapeutic options for downstaging advanced HCC prior to LT. Somehow, advanced HCC with PVTT could be downstaged to become eligible for LT through these multidisciplinary approaches. Although the available evidence of LT for HCC with PVTT is limited, it is hoped that LT may soon be more widely indicated for these patients. Nevertheless, several unknown factors associated with LT for HCC remain to be explored. Herein, this review aimed to update the developments in LT for patients with advanced HCC.

Efficacy and safety of TACE combined with ablation and regorafenib for unresectable hepatocellular carcinoma: A real-world study.

e16170 Background: The purpose of our study was to determine the efficacy and safety of transarterial chemoembolization (TACE) combined with regorafenib as second-line therapy in patients with unresectable hepatocellular carcinoma (HCC). Methods: Patients with HCC at Barcelona Clinic Liver Cancer (BCLC) stage B or C who received the combined treatment of TACE, ablation, and regorafenib or regorafenib plus anti-PD-1 immune checkpoint inhibitors (ICIs) in Youan hospital between April 2020 to June 2023 were reviewed. The primary end-point was progression-free survival (PFS). Overall survival (OS), objective response rate (ORR), disease control rate (DCR), and toxicity were the secondary endpoints. Results: A total of 73 patients were enrolled in our study, including 63 (86.3%) males and 10 (13.7%) females. 16 (21.9%) patients had portal vein tumor thrombosis (PVTT) and 33 (45.2%) patients had extrahepatic metastasis. There were 53 (72.6%) patients with multiple tumor numbers and 23 (31.5%) patients with large tumors (≥30mm). All patients received TACE combined with regorafenib, while 37 (50.7%) patients plus ICIs and 36 (49.3%) patients not plus with ICIs. Besides, the majority of patients (N=61, 83.6%) in our cohort received ablation. The patients with AFP&gt;400U/L were 22 (20.1%). The average follow-up of the cohort was 24.6 months. The median PFS was 7.06 months (95%CI: 4.77-9.36 months) and the median OS was 23.47 months (9.79-37.15 months). Treatment response is shown in Table 2. According to mRECIST criteria, the ORR was 58.9% and the DCR was 91.8%, respectively. No adverse effects (AEs) were reported in the 11 patients in the study. The most common any-grade treatment-related AEs were hand-foot syndrome (21.9%), diarrhea (23.28%), and hypertension (21.9%). Grade≥3 treatment-related AE occurred in 12.3% of the patients. The most common grade 3 treatment-related AE was hypertension (5.48%). Conclusions: TACE combined with ablation and regorafenib is an effective, safe, and promising second-line treatment option for patients with unresectable HCC after progression from first-line therapy. [Table: see text]

Hepatic artery infusion chemotherapy combined with immune checkpoint inhibitors and tyrosine kinase inhibitors for advanced hepatocellular carcinoma with portal vein tumor thrombus: A single center retrospective study.

e16176 Background: Hepatic artery infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs, a triplet regimen) has shown promising results in advanced hepatocellular carcinoma (HCC); however, the real world outcomes for pts with portal vein tumor thrombosis (PVTT) need further clarification. This study aimed to investigate the effectiveness of the triplet regimen in HCC pts with PVTT. Methods: We retrospectively included pts who received HAIC plus anti-PD-1 antibodies, bevacizumab or lenvatinib as first-line therapy for HCC pts with PVTT between Apr 2021 and Dec 2022. Pts received HAIC of mFOLFOX (oxaliplatin, 85 mg/m2; leucovorin, 400 mg/m2; 5-fluorouracil bolus, 400 mg/m2 on day 1; 5-fluorouracil infusion, 2400 mg/m2 for 46 h). The combination of TKIs and ICIs included 6 patterns: tislelizumab and lenvatinib (TIS-LEN), sintilimab and lenvatinib (SIN-LEN), pembrolizumab and lenvatinib (PEM-LEM), camrelizumab and lenvatinib (CAM-LEN), sintilimab and bevacizumab (SIN-BEV), and atezolizumab and bevacizumab (ATE-BEV). Primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), objective response rate (ORR) and safety. Results: A total of 113 pts were included, with a median age of 55 years (range 48-60). Pts characteristics were as follows: male (90.3%), hepatitis B (81.4%), BCLC C stage (100%), Child-Pugh A (92.9%), tumor number [ = 1 (45.1%), = 2 (10.6%), ≥3 (44.3%)], tumor diameter&gt;10 cm (43.4%), extrahepatic metastasis (19.5%), beyond up to steven status (88.5%). Specific treatment options are as follows: HAIC-TIS-LEN (n = 57), HAIC-SIN-LEN (n = 21), HAIC-PEM-LEM (n = 6), HAIC-CAM-LEN (n = 12), HAIC-SIN-BEV (n = 14), and HAIC-ATE-BEV (n = 3). As of Dec 31, 2023, the median follow-up duration was 18.4 mo (95% CI, 16.7-25.1), and the median number of HAIC was 2.5 (range 2-3). The median PFS was 8.1 months (95% CI, 6.8-9.8), while the median OS reached 17.7 months (95% CI:14.5-27.6). ORR was 51.3% (3 CR, 55PR), DCR was 91.2% per RECIST 1.1; ORR was 64.6% (18 CR, 55 PR), DCR was 92% per mRECIST. 15 pts (13.3%) received surgical treatment after conversion, 13 of whom remains tumor-free to date. Among those who develop disease progression, 35.3% pts (29/83) underwent a subsequent regimen that included TACE. The most common TRAEs were hypoalbuminemia (41.6%), abdominal pain (36.3%), anorexia (33.6%), hypertension (27.4%) and hypothyroidism (25.6%). The most common grade 3-4 TRAEs included hypertension (10.6%), leukocytes count decreased (9.7%), abdominal pain (8.8%), proteinuria (6.2%) and hypoalbuminemia (5.3%). Conclusions: This study further demonstrates the clinical benefit of HAIC plus ICIs and TKIs for HCC pts with PVTT. In the future, prospective studies are warranted.

TACE-HAIC combined with donafenib and immunotherapy for hepatocellular carcinoma (HCC) with portal vein tumour thrombus (PVTT): A retrospective analysis.

e16174 Background: The probability of Chinese hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) is relatively large and the long-term survival of this part of patients is poor. Systemic therapy, transcatheter arterial chemoembolization (TACE), and hepatic artery infusion chemotherapy are widely used in HCC patients with PVTT. We want to explore the efficacy and safety of TACE plus hepatic arterial infusion chemotherapy combined with Donafenib, anti-PD-1 antibody in uHCC patients with PVTT. Methods: We retrospectively analyzed the patients who were diagnosed as uHCC with PVTT and received the treatment of TACE plus HAIC combined with Donafenib, anti-PD-1 antibody as first-line therapy from Dec 2021 to Jun 2023 in Harbin Medical University Cancer Hospital. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progress free survival (PFS), overall survival (OS) and safety. Results: Of 106 patients included in the analysis, all of them received first-line treatment of TACE (embolization of pirarubicin hydrochloride 40mg, iodized oil 10-20ml with or without gelatin sponge) plus HAIC (oxaliplatin 85 mg/m2 2h, leucovorin 400 mg/m2 1h, fluorouracil bolus 400 mg/m2 in the first 10 minutes, and fluorouracil infusion 2400 mg/m2 for 46h) combined with donafenib 200mg bid, anti-PD-1 antibody Q3W. The median age was 58 years (IQR, 52-64). The study population was predominantly male (79.2%), and 79.2% were HBV-positive. All HCC patients are accompanied by PVTT, most of which are VP3(72.6%).The rate of patients with extrahepatic metastasis were 16.0%. All patients were classified as BCLC stage C and 84.0% were classified as CNLC stage IIIa. As of December 2023, 106 patients had received at least one imaging evaluation, 11 (10.4%), 60 (56.6%) and 28 (26.4%) of them achieved complete response, partial response and stable disease, and the overall objective response rate and disease control rate was 67.0% and 93.4% per modified RECIST criteria respectively. With 16.3 months of median follow-up time, the 12-month PFS rate was 81.3% and the 12-month OS rate was 90.1%. The median PFS and OS were not reached. 103 of all patients had at least one treatment-related AE (TRAE), and treatment-related deaths did not occur in this study. Grade 3 TRAEs occurred in 33 (31.1%) patients, and no grades 4 or 5 were reported. The most common Grade 3 TRAEs included aspartate transaminase increased (18.9%), platelet count decreased (14.2%) and blood bilirubin increased (8.5%). Conclusions: TACE-HAIC combined with Donafenib and immunotherapy are effective and tolerable for uHCC patients with PVTT.

Clinical risk factors for portal hypertension-related complications in systemic therapy for hepatocellular carcinoma.

During systemic therapy, the management of portal hypertension (PH)-related complications is vital. This study aimed to clarify factors associated with the incidence and exacerbation of PH-related complications, including the usefulness of contrast-enhanced computed tomography (CECT) in the management of PH-related complications during systemic therapy. A total of 669 patients who received systemic therapy as first-line treatment (443 patients for sorafenib, 131 for lenvatinib, and 90 for atezolizumab/bevacizumab [ATZ/BEV]) were enrolled in this retrospective study. Additionally, the lower esophageal intramural vessel diameters (EIV) on CECT and endoscopic findings in 358 patients were compared. The cutoff values of the EIV diameter on CECT were 3.1mm for small, 5.1mm for medium, and 7.6mm for large varices, demonstrating high concordance with the endoscopic findings. esophageal varices (EV) bleeding predictors include EIV ≥ 3.1mm and portal vein tumor thrombosis (PVTT). In patients without EV before systemic therapy, factors associated with EV exacerbation after 3months were EIV ≥ 1.9mm and ATZ/BEV use. Predictors of hepatic encephalopathy (HE) include the ammonia level or portosystemic shunt diameter ≥ 6.8mm. The incidence of HE within 2weeks was significantly higher (18%) in patients with an ammonia level ≥ 73μmol/L and a portosystemic shunt ≥ 6.8mm. The exacerbating factors for ascites after 3months were PVTT and low albumin levels. Careful management is warranted for patients with risk factors for exacerbation of PH-related complications; moreover, the effective use of CECT is clinically important.

Transcriptomic and genomic characteristics of intrahepatic metastases of primary liver cancer

BackgroundPatients with primary multifocal hepatocellular carcinoma (HCC) have a poor prognosis and often experience a high rate of treatment failure. Multifocal HCC is mainly caused by intrahepatic metastasis (IM), and though portal vein tumor thrombosis (PVTT) is considered a hallmark of IM, the molecular mechanism by which primary HCC cells invade the portal veins remains unclear. Therefore, it is necessary to recognize the early signs of metastasis of HCC to arrange better treatment for patients.ResultsTo determine the differential molecular features between primary HCC with and without phenotype of metastasis, we used the CIBERSORTx software to deconvolute cell types from bulk RNA-Seq based on a single-cell transcriptomic dataset. According to the relative abundance of tumorigenic and metastatic hepatoma cells, VEGFA+ macrophages, effector memory T cells, and natural killer cells, HCC samples were divided into five groups: Pro-T, Mix, Pro-Meta, NKC, and MemT, and the transcriptomic and genomic features of the first three groups were analyzed. We found that the Pro-T group appeared to retain native hepatic metabolic activity, whereas the Pro-Meta group underwent dedifferentiation. Genes highly expressed in the group Pro-Meta often signify a worse outcome.ConclusionsThe HCC cohort can be well-typed and prognosis predicted according to tumor microenvironment components. Primary hepatocellular carcinoma may have obtained corresponding molecular features before metastasis occurred.

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.

Distinct Characteristics and Changes in Liver Function of Patients with Hepatocellular Carcinoma Treated with Atezolizumab Plus Bevacizumab for More Than 1 Year.

Since 2020, atezolizumab plus bevacizumab (Ate/Bev) has been the standard first-line therapy for unresectable hepatocellular carcinoma (HCC), but long-term treatment studies are limited. This study evaluated the clinical characteristics and effects of Ate/Bev for over 1 year. This study included patients with unresectable HCC treated with first-line Ate/Bev between May 2020 and April 2022. Those receiving Ate/Bev for 1 year or more were classified as the long-term treatment group. Of 246 patients, 69 (28.0%) were in the long-term treatment group, which comprised more proportions of intrahepatic tumor burden < 25%, Eastern Cooperative Oncology Group 0, and a lower proportion of portal vein tumor thrombosis than the short-term treatment group. The long-term treatment group had a higher incidence of atezolizumab-related thyroid dysfunction (31.9% vs. 10.7%, p < 0.001; median time to onset [mTTO], 2.8 months), dermatologic toxicity (29.0% vs. 14.7%, p=0.017; mTTO, 3.3 months), bevacizumab-related hypertension (44.9% vs. 22.0%, p=0.001; mTTO, 4.2 months), and proteinuria (69.6% vs. 38.4%, p < 0.001; mTTO, 6.8 months), compared to the short-term treatment group. Regarding liver function in the long-term treatment group, patients initially classified as Child-Pugh class A decreased from 87.0% to 75.4%, and albumin-bilirubin grade 1 decreased from 68.1% to 50.7% after 1 year of treatment. The Ate/Bev long-term treatment group had a lower intrahepatic tumor burden, less portal vein tumor thrombosis, and better performance status and liver function at baseline. Atezolizumab-related immunological adverse events emerged relatively early in treatment compared to the bevacizumab-related. Additionally, some patients demonstrated liver function deterioration during long-term Ate/Bev treatment.

Commentary on "Comparison between laparoscopic liver resection and open liver resection in patients with hepatocellular carcinoma with portal vein tumor thrombosis".

Commentary on "Comparison between laparoscopic liver resection and open liver resection in patients with hepatocellular carcinoma with portal vein tumor thrombosis".

Liver Resection Under Total Hepatic Vascular Exclusion with In Situ Hypothermic Isolated Hepatic Perfusion for Advanced Liver Tumors.

Continuous dissection or simultaneous reconstruction of the hepatic vein (HV) and inferior vena cava (IVC) was achieved under total hepatic vascular exclusion (THVE) with in situ hypothermic isolated hepatic perfusion (HIHP) in two cases. CASE 1: The patient previously underwent liver resections with the right HV for colorectal liver metastasis (CRLM). This time, the CRLM had invaded the left HV and IVC, and five courses of FOLFILI plus ramucirumab were given, resulting in stable disease. Due to expected high HV pressure, liver parenchymal transection was started under THVE. Sub-segmentectomy with patch graft plasty of the IVC and reconstruction of the left HV using a jugular vein graft were performed under THVE and HIHP. This patient died at home 3 months after surgery; the cause of death was unknown. CASE 2: Hepatocellular carcinoma in the caudate lobe was in extensive contact with the roots of three main HVs and the IVC, and pressed the hepatocaval confluence, with high HV pressure expected. In addition, tumor thrombosis extended to both the main portal vein and the common bile duct, resulting in the inability to introduce chemotherapy. After tumor thrombectomy, liver parenchymal transection was started under THVE. Extended left hepatectomy with wedge resection, and primary suture of the right HV and IVC was performed under THVE and HIHP. Recurrence-free and overall survivals were 8 months (lung metastasis) and 31 months, respectively. In liver resection for liver tumors located in the hepatocaval confluence, THVE with HIHP is useful for ensuring the safety.

Advancements in hepatocellular carcinoma management: the role of 18F-FDG PET-CT in diagnosing portal vein tumor thrombosis.

Portal vein thrombosis, a relatively frequent complication associated with hepatocellular carcinoma (HCC) and liver cirrhosis, is recognized as a significant global health concern. This is mainly due to these conditions' high prevalence and potentially severe outcomes. The aim of our study was to conduct a comprehensive literature review to evaluate the efficacy, accuracy, and clinical implications of 18F-FDG PET-CT in diagnosing and managing portal vein tumor thrombosis (PVTT) in patients with HCC. HCC, which accounts for 80% of liver malignancies, ranks as the fourth most prevalent cancer globally and is a significant contributor to cancer-related mortality. The majority of HCC patients are diagnosed at an advanced stage, leading to a deterioration in patient outcomes. Involvement of the portal vein is also a significant negative factor. This review analyzes the application of 18F-FDG PET-CT in the detection and management of PVTT in patients with HCC, with an emphasis on the importance of the maximum standardized uptake value as an essential diagnostic and prognostic marker. 18F-FDG PET-CT is invaluable for detecting recurrence and guiding management strategies, particularly in patients with high-grade HCC, and plays a pivotal role in differentiating malignant portal vein thrombi from their benign counterparts.

Interventional therapy combined with tyrosine kinase inhibitors with or without immune checkpoint inhibitors as initial treatment for hepatocellular carcinoma with portal vein tumor thrombosis: a systematic review and meta-analysis

BackgroundInterventional therapy, in conjunction with tyrosine kinase inhibitors (TKIs), has shown promising outcomes for treating hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). With the advent of immunotherapy, the combined use of immune checkpoint inhibitors (ICIs) has attracted great attention due to their potential effectiveness in advanced HCC. This study aims to compare the efficacy and safety of a triple therapy regimen (Interventional therapy, TKIs and ICIs, IT-TKI-ICI) with a dual therapy regimen (Interventional therapy and TKIs, IT-TKI) in the treatment of HCC and PVTT (HCC-PVTT).MethodsA comprehensive search was carried out in PubMed, Web of Science, Embase, Scopus, and the Cochrane Library databases. Primary outcome measures were overall survival (OS) and progression-free survival (PFS), while secondary outcomes included tumor response rate, adverse event incidence as well as downstaging surgery rate. Statistical analysis was conducted using Revman 5.4 software.ResultsThe meta-analysis finally included 6 cohort studies. The triple therapy group demonstrated significantly prolonged OS and PFS compared to the dual therapy group. Meanwhile, the former exhibited significantly higher rates of objective response rate (ORR), disease control rate (DCR) and better downstaging effects with a higher salvage surgery rate without significantly increasing adverse events.ConclusionIn comparison to dual therapy, the triple therapy with interventional therapy, TKIs, and ICIs demonstrates superior efficacy and equivalent safety for HCC-PVTT.