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Portal vein tumor thrombosis (PVTT) is an intractable condition but common phenomenon in hepatocellular carcinoma (HCC). HCC patients with PVTT may have worse liver function, a higher chance of comorbidity related to portal hypertension, lower tolerance to treatment and poorer prognoses. In Western guidelines, patients are offered palliative treatm...
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Context 1
... third PVTT classification system was published in 2007 by Cheng and coworkers 26 and has been accepted by many liver centers in China. This system includes four types of PVTT (Table 3). In a subsequent retrospective study of 441 patients who underwent partial hepatic resection with or without portal thrombectomy for HCC with PVTT, the percentages of patients with types I, II, III and IV PVTT were 32.7%, 42.9%, 19.5% and 5.0%, respectively. ...
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Background:
Whether clinically significant portal hypertension (CSPH) is a contraindication of partial hepatectomy for patients with hepatocellular carcinoma (HCC) remains controversial. The aim was to assess the impact of CSPH on surgical morbidity, mortality and long-term survival of HCC patients who underwent partial hepatectomy.
Methods:
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Citations
... MVI is present in advanced HCC approximately 10-60% of patients at diagnosis. 20 Portal vein tumor thrombosis is the most common form of MVI, which is divided into 4 types from Vp1 to Vp4, according to the severity of tumor thrombosis and anatomic structures of the portal vein. 21 The growth pattern of MVI is predominantly characterized by invasion from intrahepatic nodules that progresses toward the central trunk, and its occurrence indicates tumor spread in the liver, resulting in a reduction in patient survival. ...
Background
The presence of macrovascular invasion (MVI) is associated with poor prognosis in advanced hepatocellular carcinoma (HCC). This study aims to evaluate the efficacy and safety of Cinobufacini therapy via hepatic arterial infusion (HAI) in advanced HCC patients with MVI.
Methods
The clinical records of 130 consecutive patients with unresectable advanced HCC and MVI who had received Cinobufacini or cisplatin plus 5-fluorouracil (CF) treatment via HAI were retrospectively analyzed. The therapeutic efficacy, overall survival (OS), progression-free survival (PFS), and adverse events were compared between the two treatment groups.
Results
The Cinobufacini group demonstrated significant curative effects on treatment via HAI compared with the CF group, including the objective response rate (44.9% vs 27.9%, P=0.048), the median OS (14.8 months vs 11.1 months, P=0.010), and the median PFS (10.3 months vs 6.0 months, P=0.006). Result in subgroup analysis of portal vein invasion grade supported the efficacy in Cinobufacini treatment, especially in the median OS of Vp1-2 (18.3 months vs 14.3 months, P=0.043) and Vp3 (15.0 months vs 11.4 months, P=0.046), as well as the median PFS of Vp1-2 (14.8 months vs 10.2 months, P=0.028) and Vp3 (10.8 months vs 6.6 months, P=0.033) compared with CF treatment. Cox proportional hazards model and forest plot analysis of factors confirmed the survival benefit from HAI with Cinobufacini over CF (hazard ratio [HR], 0.61; 95% CI: 0.40–0.91; P=0.010). Multivariable analysis identified portal vein invasion grade (Vp4; HR, 1.78; 95% CI: 1.03–2.16; P=0.032) and AFP (>1000; HR, 1.61; 95% CI: 1.08–1.91; P=0.039) as the independent factors for prognosis. Moreover, the total incidence of adverse events in the Cinobufacini group was significantly lower than in the CF group (60.9% vs 82.0%, P=0.009).
Conclusion
Cinobufacini therapy via HAI is a viable strategy for curing advanced HCC with MVI, due to prolonged survival and a superior safety profile.
... Around 10%-60% of patients diagnosed with PVTT have entered intermediate and advanced stages with the deterioration of liver function, which leads to intrahepatic and distant metastasis, contributing to merely around 2.7 months of the median survival time in patients with HCC-PVTT after receiving supportive care. Therefore, preventing PVTT occurrence in patients with HCC clinically represents tertiary prevention [6,7] . Presently, PVTT is categorized into six grades by the Liver Cancer Study . ...
Portal vein tumor thrombus (PVTT) in hepatocellular carcinoma (HCC) represents a worse liver function, less treatment tolerance, and poor prognosis. Here, this study aims to explore whether a combination of the DeRitis ratio (AST/ALT) and alkaline phosphatase (ALP) index (briefly named DALP) availably predicts the occurrence risk of PVTT in patients with HCC. We performed a retrospective study enrolling consecutive patients with HCC from January 2017 to December 2020 in Hebei Medical University Third Hospital. ROC analysis was performed to estimate the predictive effectiveness and optimal cut-off value of DALP for PVTT occurrence in patients with HCC. Kaplan-Meier analysis revealed the survival probabilities in each subgroup according to the risk classification of DALP value. Univariate and multivariate Logistics regression analyses were applied to determine the independent risk for poor prognosis. ROC analysis revealed that the optimal cut-off value for DALP was 1.045, with an area under the curve (AUC) of 0.793 (95% CI: 0.697-0.888). Based on the DALP classification (three scores: 0-2) with distinguishable prognoses, patients in the score 0 group had the best prognosis with a 1-year overall survival (OS) of 100%, whereas score 2 patients had the worst prognosis with 1-year OS of 72.4%. Similarly, there was a statistically different recurrence-free survival among the three groups. Besides, this risk classification was also associated with PVTT progression in HCC patients (odds ratio [OR]:5.822, P < 0.0001). Pathologically, patients in the score 2 group had more advanced tumors considering PVTT, extrahepatic metastasis, and ascites than those in score 0, 1 groups. Moreover, patients with a score of 2 had more severe hepatic inflammation than other groups. Combination of DeRitis ratio and ALP index presented a better predictive value for PVTT occurrence in patients with HCC, contributing to the tertiary prevention.
... The symptoms of early HCC are often imperceptible, and approximately 70%-80% of patients are diagnosed at an advanced stage (2). In HCC involving the invasion of intrahepatic blood vessels (portal or hepatic vein branches), patients are less tolerant to treatment and only survive for approximately 2-4 months without treatment (3,4). Studies have found that HCC prognosis is related to the presence and extent of portal vein tumor thrombus (PVTT) (5). ...
Background
Portal vein tumor thrombus (PVTT) is a common complication and an obstacle to treatment, with a high recurrence rate and poor prognosis. There is still no global consensus or standard guidelines on the management of hepatocellular carcinoma (HCC) with PVTT. Increasing evidence suggests that more aggressive treatment modalities, including transarterial chemoembolization, radiotherapy, targeted therapy, and various combination therapies, may improve the prognosis and prolong the survival of advanced hepatocellular carcinoma (aHCC) patients with PVTT. We aim to comprehensively review and compare the efficacy and safety of these advanced options for aHCC with PVTT.
Methods
A comprehensive literature search was conducted on PubMed and EMBASE for phase II or III randomized controlled trials (RCTs) investigating multimodality treatments for aHCC with PVTT. Kaplan–Meier curves for overall survival (OS) and progression-free survival were constructed to retrieve individual patient-level data to strengthen the comparison of the benefits of all multimodality treatments of interest. Each study was pooled in a fixed-effects network meta-analysis (NMA). We also conducted subgroup analyses using risk ratios extracted from each study, including viral etiology, Barcelona Clinic Liver Cancer (BCLC) staging, alpha-fetoprotein (AFP) levels, macrovascular invasion or portal vein tumor thrombosis, and extrahepatic spread. Multimodality treatments were ranked using SUCRA scores.
Results
We identified 15 randomized controlled trials with 16 multimodality regimens that met the inclusion criteria. Among them, 5,236 patients with OS results and 5,160 patients with PFS results were included in the analysis. The hepatic arterial infusion chemotherapy of fluorouracil, leucovorin, and oxaliplatin (HAIC-FO) showed OS and PFS benefits over all the other therapies. In terms of OS, HAIC-FO, nivolumab, and TACE+Len were superior to sorafenib, lenvatinib, and donatinib monotherapies, as well as HAIC-FO+Sor. In terms of PFS, TACE+Len showed better benefits than lenvatinib, donatinib, and tremelimumab+durvalumab. A low heterogeneity ( I ² < 50%) and consistency were observed. The SUCRA score for OS ranked HAIC-FO+sorafenib as the best treatment option among all multimodality treatments in hepatitis B, MVI, or PVTT with EHS and AFP 400 μg/L subgroups.
Conclusion
HAIC-FO and HAIC-FO+sorafenib are statistically better options for unresectable hepatocellular carcinoma with PVTT among the multimodality treatments, and their effective and safe implementation may provide the best outcomes for HCC-PVTT patients.
... In recent years, more treatment options have been developed for patients with HCC with PVTT which has led to significant improvements in patient prognosis. [10][11][12][13] For example, advancements in radiotherapy technology have realized the use of local radiotherapy as an effective treatment option for PVTT. A study by a Chinese research team confirmed that, compared with surgery alone, surgery after radiotherapy prolonged the progression-free survival (PFS) and overall survival (OS) of liver cancer patients with PVTT. ...
Background
Patients with hepatocellular carcinoma (HCC) with portal vein tumour thrombus (PVTT), especially type Vp-4, usually have a poor prognosis. However, the vast majority of Phase III clinical trials exclude this population based on the inclusion criteria. Lenvatinib plus a PD-1 inhibitor has shown promising antitumour activity and tolerable safety in patients with unresectable HCC in Asian populations. Radiotherapy has also demonstrated high response rates and favourable survival for HCC patients with PVTT. This study aimed to explore the preliminary clinical efficacy and safety of lenvatinib plus the PD-1 inhibitor combined with radiotherapy for HCC patients with main portal vein tumour thrombus.
Methods
Between 1 March 2018 and 31 October 2020, HCC patients with main PVTT who received lenvatinib plus a PD-1 inhibitor (pembrolizumab, nivolumab or sintilimab) combined with radiotherapy from Beijing Tsinghua Changgung Hospital in China were reviewed for eligibility. The efficacy was evaluated by the survival and PVTT response rate, and the safety was evaluated by the frequency of key adverse events (AEs).
Results
In total, 39 eligible HCC patients with type Vp-4 PVTT who received triple therapy were included in this study. The 2-year OS rate was 15.4%, which was the primary end-point of our study. The median overall survival (OS) and progression-free survival (PFS) were 9.4 months (range 2.3 to 57.1) and 4.9 months (range 1.4 to 36.1), respectively. The objective response rate (ORR) of PVTT based on mRECIST was 61.5%. AFP dropped to normal 3 months after radiotherapy and was an independent risk factor associated with OS. All AEs were controlled, and no treatment-related deaths occurred.
Conclusion
Lenvatinib plus PD-1 inhibitor combined with radiotherapy had a significant therapeutic effect and manageable AEs in HCC patients with type Vp-4 PVTT and may be a potential treatment option for advanced HCC.
... Metastasis is a defining characteristic of cancer [6]. HCC tends to invade the vascular system to form microvascular invasion (MVI) or portal vein tumor thrombosis (PVTT) [7]. Vascular invasion is a major route for intrahepatic and distant metastasis in HCC and is a strong negative prognostic factor [8]. PVTT is present in 10-60% of patients at the time of initial diagnosis of HCC [9]. ...
Background
Vascular invasion is a major route for intrahepatic and distant metastasis in hepatocellular carcinoma (HCC) and is a strong negative prognostic factor. Circular RNAs (circRNAs) play important roles in tumorigenesis and metastasis. However, the regulatory functions and underlying mechanisms of circRNAs in the development of vascular invasion in HCC are largely unknown.
Methods
High throughput sequencing was used to screen dysregulated circRNAs in portal vein tumor thrombosis (PVTT) tissues. The biological functions of candidate circRNAs in the migration, vascular invasion, and metastasis of HCC cells were examined in vitro and in vivo. To explore the underlying mechanisms, RNA sequencing, MS2-tagged RNA affinity purification, mass spectrometry, and RNA immunoprecipitation assays were performed.
Results
circRNA sequencing followed by quantitative real-time PCR (qRT-PCR) revealed that circRNA pleckstrin and Sect. 7 domain containing 3 (circPSD3) was significantly downregulated in PVTT tissues. Decreased circPSD3 expression in HCC tissues was associated with unfavourable characteristics and predicted poor prognosis in HCC. TAR DNA-binding protein 43 (TDP43) inhibited the biogenesis of circPSD3 by interacting with the downstream intron of pre-PSD3. circPSD3 inhibited the intrahepatic vascular invasion and metastasis of HCC cells in vitro and in vivo. Serpin family B member 2 (SERPINB2), an endogenous bona fide inhibitor of the urokinase-type plasminogen activator (uPA) system, is the downstream target of circPSD3. Mechanistically, circPSD3 interacts with histone deacetylase 1 (HDAC1) to sequester it in the cytoplasm, attenuating the inhibitory effect of HDAC1 on the transcription of SERPINB2. In vitro and in vivo studies demonstrated that circPSD3 is a promising inhibitor of the uPA system.
Conclusions
circPSD3 is an essential regulator of vascular invasion and metastasis in HCC and may serve as a prognostic biomarker and therapeutic target.
... A subgroup analysis of a phase III trial investigating the efficacy of sorafenib in patients with locally advanced HCC revealed that while sorafenib improved OS and time to progression compared with placebo, the benefit decreased in patients with macrovascular invasion [24]. On the other hand, a high response rate of PVTT to RT has been reported previously [12,25,26], and it could be further improved when multimodal treatment, such as HAIC in combination with RT, is administered [2]. The tumor downstaging rate of our group was comparable to that of other groups-a recent study from a Japanese group reported tumor downstaging in 11.8% of patients after combination therapy of HAIC and RT [22]. ...
Purpose:
Although systemic treatment is the mainstay for advanced hepatocellular carcinoma (HCC), numerous studies have highlighted the added value of local treatment. This study aimed to investigate the clinical efficacy of liver-directed combined radiotherapy (LD combined RT) compared with that of sorafenib, a recommended treatment until recently for locally advanced HCC presenting portal vein tumor thrombosis (PVTT), using a multinational patient cohort.
Materials and methods:
We identified patients with HCC presenting PVTT treated with either sorafenib or LD combined RT in 10 tertiary hospitals in Asia from 2005 to 2014. Propensity score matching (PSM) was performed to minimize the imbalance between the two groups. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS) and treatment-related toxicity.
Results:
A total of 1035 patients (675 in the LD combined RT group and 360 in the sorafenib group) were included in this study. After PSM, 305 patients from each group were included in the analysis. At a median follow-up of 22.5 months, the median OS was 10.6 and 4.2 months for the LD combined RT and sorafenib groups, respectively (p < 0.001). The conversion rate to curative surgery was significantly higher (8.5% vs. 1.0%, p < 0.001), while grade ≥ 3 toxicity was fewer (9.2% vs. 16.1%, p < 0.001) in the LD combined RT group.
Conclusions:
LD combined RT improved survival outcomes with a higher conversion rate to curative surgery in patients with locally advanced HCC presenting PVTT. Although further prospective studies are warranted, active multimodal local treatment involving radiotherapy is suggested for locally advanced HCC presenting PVTT.
... Strict adherence to BCLC guidelines for surgical indications may prevent many patients from undergoing radical surgical treatment. In contrast, some procedures that exceed BCLC guidelines are often performed in the Asia-Pacific region, including some stage B and stage C patients (5,6), and some studies have confirmed that surgery has more favorable outcomes than other modalities (7)(8)(9). However, a wider range of surgical indications also means a higher probability of accompanying high-risk factors for recurrence. ...
Curative surgical treatments, mainly liver resection, are still one of the optimal options for patients with early-, mid-, and even progression-stage hepatocellular carcinoma (HCC). However, the recurrence rate within 5 years after surgery is as high as 70%, especially in patients with high risk factors for recurrence, most of whom experience early recurrence within 2 years. Effective adjuvant therapy may improve prognosis, previous studies found that adjuvant transarterial chemoembolization, antiviral, and traditional Chinese medicine et al. were helpful in preventing HCC recurrence. Nevertheless, due to controversial results or lack of high-level evidence, there is no standardized postoperative management protocol worldwide at present. Continued exploration of effective postoperative adjuvant treatments to improve surgical prognosis is necessary.
... A median survival ranging from 8 to 22 months has been reported for HCC patients with PVTT after surgical treatment (25,26). In our study, the median survival time was 12.4 months, which was similar to previous studies (27). These results show that hepatectomy is a safe and effective treatment for HCC patients with PVTT. ...
Background
There is no reported resolving whether microvascular invasion (MVI) affects the prognosis of hepatectomy for HCC patients with portal vein tumor thrombus (PVTT). The present study aimed to investigate the effect of MVI on HCC with PVTT after Hepatectomy.
Methods
A retrospective cohort study consisting of 362 HCC patients with PVTT was included in this study. The log-rank test was utilized to differentiate OS and RFS rates between the two groups. Univariate and multivariate Cox proportional hazard regression was utilized to detect independent factors.
Results
PVTT without MVI accounted for 12.2% (n = 44). PVTT without MVI groups was significantly superior to PVTT with MVI groups in OS and RFS. The 1-, 3-, and 5-year OS rates (65.5%, 36.8%, 21.7% vs. 53.5%, 18.7%, 10.1%, p = 0.014) and RFS rates (47.0%, 29.7%, 19.2% vs. 28.7%, 12.2%, 6.9%, p = 0.005) were significant differences between two groups. Multivariate analysis showed that MVI was the independent risk factor for OS and RFS.
Conclusions
MVI was an independent prognostic factor closely linked to tumor recurrence and poorer clinical outcomes for HCC patients with PVTT after liver resection. MVI should be included in current PVTT systems to improve the accuracy of PVTT typing.
... Although TACE is considered the preferential palliative therapy for multinodular PLC, its usefulness in PVTT, especially in type III/IV, remains uncertain. Based on their own willingness, we put some effort on those patients with PVTT involving multiple hepatic segments or portal vein trunk to choose endovascular RFA, because in these patients the liver function was more likely to be impaired with significantly reduced blood supply, furthermore, the tumor embolus were more likely to disseminate in liver and lead to shorter median survival time [3]. ...
Background
Portal vein tumor thrombosis (PVTT) secondary to primary liver carcinoma (PLC) is commonly associated with poor prognosis and poses great challenge. This study was to evaluate the efficacy and safety of percutaneous endovascular radiofrequency ablation (RFA) in treatment of PVTT.
Methods
Consecutive patients who were performed endovascular RFA because of PVTT in single-institution in recent 8 years were retrospectively reviewed, compared with patients who underwent only sequential transcatheter arterial chemoembolization (TACE) during the contemporary period. Patency of portal vein, complications, and overall survival (OS) were investigated.
Results
One hundred and 20 patients who underwent endovascular RFA and 96 patients who underwent only sequential TACE were included. No severe complications happened in both groups. Except the higher rates of severe fever and moderate pain in the study group, no difference was found in the incidence of side effects and complications. The effective rate in the study group was (78.3%, 94/120) significantly higher than the comparison group (35.4%, 34/96). The median survival time and 1–3 years cumulative survival rates in the study group were 15.7 months and 42.5%, 21.7%, 2.5%, respectively, and 11.3 months, 21.9%, 9.4%, 0 correspondingly in the comparison group, without significant difference. Type of PVTT and Child–Pugh classification of liver function were independent risk factors, and OS was significantly improved by endovascular RFA and subsequent therapy.
Conclusion
Endovascular RFA is technically safe and feasible for unresectable PLC and PVTT to improve the prognosis and quality of life.
... Presence of TIV is considered an absolute contraindication for orthotopic liver transplantation by United Network of Organ Sharing (UNOS) [34]. Certain therapeutic approaches such as hepatic resection, trans-arterial chemoembolization, trans-arterial radioembolization, or a combination of therapies may be considered for a select group of patients (mainly with TIV in segmental or sub-segmental distribution and preserved liver function) as clinical trials [33,35,36]. ...
Vascular invasion by hepatocellular carcinoma (HCC), also known as tumor in vein (TIV), indicates highly invasive tumor behavior and is also associated with poor outcome. Because a diagnosis of TIV precludes liver transplantation, knowledge of the imaging findings to differentiate between TIV and bland thrombus is key for proper patient management. Prior versions of liver imaging reporting and data system (LI-RADS) included presence of TIV as part of LR-5 criteria. However, even if HCC is the most common liver malignancy associated with TIV, other tumors can have vascular invasion and may occur in cirrhotic patients. For these reasons, in LI-RADS v2017 LR-TIV has been introduced as a new different diagnostic category. The aim of this article is to discuss the diagnostic criteria of LR-TIV according to LI-RADS v2018 and analyze potential pitfalls encountered on daily clinical practice. Indeterminate cases and how to manage them will also be discussed.
