Main Portal Vein Tumor Thrombosis Research Articles

Transarterial chemoembolization plus stent placement for hepatocellular carcinoma with main portal vein tumor thrombosis: A meta-analysis.

Portal vein tumor thrombus is an important indicator of poor prognosis in patients with hepatocellular carcinoma. Transarterial chemoembolization is recommended as the standard first-line therapy for unresectable hepatocellular carcinoma. Portal vein stent placement is a safe and effective therapy for promptly restoring flow and relieving portal hypertension caused by tumor thrombus. To assess the clinical significance of transarterial chemoembolization plus stent placement for the treatment of hepatocellular carcinoma with main portal vein tumor thrombosis. We searched English and Chinese databases, assessed the quality of the included studies, analyzed the characteristic data, tested heterogeneity, explored heterogeneity, and tested publication bias. In total, eight clinical controlled trials were included. The results showed that the pressure in the main portal vein after stent placement was significantly lower than that with no stent placement. The cumulative stent patency and survival rates at 6 and 12 months were lower in the transarterial chemoembolization + stent placement group than in the transarterial chemoembolization + stent placement + brachytherapy/radiotherapy group. The survival rates of patients treated with transarterial chemoembolization + stent placement for 6 and 12 months were higher than those of patients treated with transarterial chemoembolization alone. For Chinese patients with hepatocellular carcinoma with main portal vein tumor thrombosis, transarterial chemoembolization plus stenting is effective. Transarterial chemoembolization + stent placement is more effective than transarterial chemoembolization alone. Transarterial chemoembolization + stent placement + brachytherapy/radiotherapy is more effective than transarterial chemoembolization + stenting.

An open-label, multi-center phase IIIb study of durvalumab and tremelimumab as first-line treatment in patients with unresectable hepatocellular carcinoma (TREMENDOUS study).

TPS628 Background: Hepatocellular carcinoma (HCC) is of high incidence and mortality rate in China, with nearly half of them are diagnosed as advanced or metastatic stage at the initial diagnosis. First-line treatment options for patients with advanced disease previously included tyrosine kinase inhibitors and immune checkpoint inhibitors in combination with vascular endothelial growth factor. Recently, the phase III HIMALAYA trial investigated the STRIDE regimen, tremelimumab 300mg × 1 dose and durvalumab 1500mg every 4 weeks, compared to sorafenib in previously untreated locally advanced or metastatic HCC patients, and resulted in significantly improved overall survival (OS) (16.4 mos vs 13.8mos, HR=0.78) and a well-tolerated safety profile (≥grade 3 treatment-related adverse events 25.8% vs 36.9% ). Notably, the HIMALAYA trial did not enroll subject from mainland China and excluded patients with class Child-Pugh B liver dysfunction or ECOG performance status (PS) 2. We hypothesize the STRIDE regimen will be safe and well tolerated in Chinese patients with locally advanced or metastatic HCC with Child-Pugh class A or B liver dysfunction or ECOG PS 0-2. In addition, the study will also assess efficacy and explore biomarkers. Methods: This will be an open label, multi-center phase IIIb study investigating the safety and efficacy of the STRIDE regimen in Chinese unresectable HCC patients without prior systemic therapy. Patients with Child-Pugh A liver dysfunction and ECOG PS 0-1 will be enrolled in cohort 1, while patients with Child-Pugh B liver dysfunction or ECOG PS 2 will be enrolled in cohort 2. Patients with main portal vein tumor thrombosis (Vp4), clinically significant ascites or hepatic encephalopathy, or active or prior documented gastrointestinal bleeding within 12 months will be excluded. We plan to enroll 300 patients with the primary endpoint of grade 3-5 adverse event (AE) rate by CTCAE v5.0 and adverse events of special interest (AESI). Secondary endpoints include objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), OS, OS rate at 6 months and 12 months. Patients of both cohorts will receive a single dose of tremelimumab 300 mg and durvalumab 1500 mg at Cycle 1 (Week 0), followed by durvalumab 1500 mg monotherapy every 4 weeks until confirmed disease progression or unacceptable toxicity. Archival or fresh tumor biopsy will be required at baseline. The trial is currently screening eligible subjects. Clinical trial information: CTR20222433 .

Transjugular intrahepatic portosystemic shunt with radioactive seed strand for main portal vein tumor thrombosis with cirrhotic portal hypertension.

BACKGROUNDPatients with hepatocellular carcinoma complicated with main portal vein tumor thrombosis (mPVTT) and cirrhotic portal hypertension (CPH) have an extremely poor prognosis, and there is a lack of a clinically effective treatment paradigm.AIMTo evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) combined with radioactive seed strand for the treatment of mPVTT patients with CPH.METHODSThe clinical data of 83 consecutive patients who underwent TIPS combined with 125I seed strand placement for mPVTT and CPH from January 2015 to December 2018 were retrospectively reviewed. Procedure-related data (success rate, relief of portal vein pressure and CPH symptoms, and adverse events), PVTT response, and patient survival were assessed through a 2-year follow-up.RESULTSThe success rate was 100.0% without perioperative death or procedure-related severe adverse events. The mean portal vein pressure was significantly decreased after the procedure (22.25 ± 7.33 mmHg vs 35.12 ± 7.94 mmHg, t = 20.61, P < 0.001). The symptoms of CPH were all effectively relieved within 1 mo. The objective response rate of PVTT was 67.5%. During a mean follow-up of 14.5 ± 9.4 mo (range 1-37 mo), the cumulative survival rates at 6, 12 and 24 mo were 83.1%, 49.7%, and 21.8%, respectively. The median survival time was 12.0 ± 1.3 mo (95% confidence interval: 9.5-14.5). In multivariate Cox regression analysis, body mass index, Child-Pugh grade, cTNM stage, and PVTT response were independent prognostic factors (P < 0.05).CONCLUSIONTIPS combined with radioactive seed strand might be effective and safe in treating mPVTT patients with CPH.

Safety and Efficacy of Liver-Directed Radiotherapy in Combination With Lenvatinib for Hepatocelluar Carcinoma With Macroscopic Tumor Thrombosis.

BackgroundThis study aimed to compare the clinical outcomes of patients with hepatocellular carcinoma (HCC) and macroscopic tumor thrombosis who were treated with lenvatinib with or without combined liver-directed radiotherapy (LRT).MethodsFrom the institutional registry, we enrolled 82 patients diagnosed with HCC involving macroscopic tumor thrombosis and treated with lenvatinib monotherapy (non-LRT group, n = 54, 65.9%) or lenvatinib in combination with LRT (LRT group, n = 28, 34.1%). Patients were classified into the LRT group if LRT was performed within 8 weeks of lenvatinib initiation.ResultsDuring the median follow-up period of 5.4 (range 1.4 to 17.5) months, there was no significant difference between the two groups in terms of overall adverse events. Although there was no statistical difference between the two groups in terms of overall response rate (32.1% vs. 20.4%, p = 0.15), a significantly higher treatment response was observed in the LRT group in terms of intrahepatic tumor response (67.9% vs. 20.4%, p < 0.001). In the LRT group, there was a slight difference in overall survival compared to the non-LRT group (64.1% in the LRT group vs. 37.7% in the non-LRT group at 12 months, hazard ratio [HR], 0.54; 95% confidence interval [CI] 0.28–1.03; p = .06), although it did not reach a statistically significant level. However, progression-free survival (PFS, 67.2% in the LRT group vs. 35.0% in the non-LRT group at 6 months, HR 0.47; 95% CI 0.27–0.82; p = 0.008) and intrahepatic progression-free survival (IHPFS, 74.3% in the LRT group vs. 43.3% in the non-LRT group at 6 months, HR 0.45; 95% CI 0.25–0.81; p = 0.008) were significantly superior in the LRT group. This result was also reproduced in the multivariate analysis adjusted for α-fetoprotein, another significant prognostic factor in this study, and the well-known prognostic factors, namely the presence of main portal vein tumor thrombosis and albumin-bilirubin grade.ConclusionsThe combination of lenvatinib and LRT is relatively safe and effective in increasing the intrahepatic tumor response and improving PFS and IHPFS in patients with HCC and macroscopic tumor thrombosis.

Hypofractionated Radiotherapy for Palliation of Main Portal Vein Tumor Thrombosis.

BackgroundHypofractionated radiotherapy delivered for portal vein tumor thrombosis (PVTT) located in the main portal vein is rarely exploited. The study aimed to evaluate the efficacy and safety of hypofractionated radiotherapy as palliative treatment for PVTT in cirrhotic patients with hepatocellular carcinoma.MethodsFrom March 2016 to July 2020, 16 patients (mean age, 59.1 ± 6.3 years; 15 men) with hepatocellular carcinoma and hepatitis virus-related cirrhosis who underwent hypofractionated radiotherapy for PVTT (located in the main portal vein) in our institute were retrospectively reviewed.ResultsComplete response of the PVTT was observed in 4 cases (25%) with partial response in 7 cases (43.75%) and stable disease in 5 cases (31.25%). Symptom relief was observed in all 7 patients suffering from ventosity. The median time to progression was 6 months (interquartile range, IQR: 6–12 months). Eight patients (50%) failed due to primary cancer progression, 7 patients failed due to extrahepatic metastasis, and only 1 patient failed due to PVTT progression. The median overall survival was 17.4 months (IQR: 8–25 months). Grade I/II anorexia/nausea was observed in 14 patients (87.5%) and Grade I/II leukopenia was observed in 14 patients (87.5%). No complications ≥ Grade III were observed.ConclusionsHypofractionated radiotherapy as palliative treatment appears effective and safe for PVTT located in the main portal vein in cirrhotic patients with advanced hepatocellular carcinoma, yielding a high rate of tumor response. Further study is warranted.

Comparison of Sorafenib versus Hepatic Arterial Infusion Chemotherapy-Based Treatment for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis.

Background/AimsSorafenib is the first approved systemic treatment for advanced hepatocellular carcinoma (HCC). However, its clinical utility is limited, especially in Asian countries. Several reports have suggested the survival benefits of hepatic arterial infusion chemotherapy (HAIC) for advanced HCC with main portal vein tumor thrombosis (PVTT). This study aimed to compare the efficacy of sorafenib-based therapy with that of HAIC-based therapy for advanced HCC with main PVTT.MethodsAdvanced HCC patients with main PVTT treated with sorafenib or HAIC between 2008 and 2016 at Korea University Medical Center were included. We evaluated overall survival (OS), time-to-progression (TTP), and the disease control rate (DCR).ResultsSeventy-three patients were treated with sorafenib (n=35) or HAIC (n=38). Baseline characteristics were not significantly different between groups, except the presence of solid organ metastasis (46% vs 5.3%, p<0.001). The median OS time was not significantly different between the groups (6.4 months vs 10.0 months, p=0.139). TTP was longer in the HAIC group than in the sorafenib group (2.1 months vs 6.2 months, p=0.006). The DCR was also better in the HAIC group than in the sorafenib group (37% vs 76%, p=0.001). Subgroup analysis, which excluded patients with extrahepatic solid organ metastasis, showed the same trends for the median OS time (8.8 months vs 11.1 months, p=0.097), TTP (1.9 months vs 6.0 months, p<0.001), and DCR (53% vs 81%, p=0.030).ConclusionsHAIC-based therapy may be an alternative to sorafenib for advanced HCC with main PVTT by providing longer TTP and a better DCR. (Gut Liver 2021;15-294)

Resection might be a meaningful choice for hepatocellular carcinoma with portal vein thrombosis: A systematic review and meta-analysis.

Background:According to the Barcelona Clinic Liver Cancer (BCLC) staging system, the presence of portal vein tumor thrombosis (PVTT) is considered to indicate an advanced stage of hepatocellular carcinoma (HCC) with nearly no cure. Hepatic resection and transarterial chemoembolization (TACE) have recently been recommended for treatment of HCC with PVTT.Methods:We conducted a systematic review to compare the overall survival between patients with HCC and PVTT undergoing hepatectomy, TACE or conservative treatment including sorafenib chemotherapy. The PubMed, Web of Science, and Cochrane Library databases were searched. All relevant studies were considered. Hazard ratios with 95% confidence intervals were calculated for comparison of the cumulative overall survival. Ten retrospective studies met the inclusion criteria and were included in the review.Results:Overall survival was not higher in the hepatectomy group than TACE group. But survival rate was higher in hepatectomy group than conservative group. The subgroup analysis demonstrated that hepatectomy was superior in patients without PVTT in the main trunk than in patients with main portal vein invasion. In patients without main PVTT, hepatectomy has showed more benefit than TACE. However, there has been no significant difference between the hepatectomy and TACE groups among patients with main PVTT.Conclusion:For patients with resectable HCC and PVTT, hepatectomy might be more effective in patients without PVTT in the main trunk than TACE or conservative treatment.

125I Irradiation Stent for Hepatocellular Carcinoma with Main Portal Vein Tumor Thrombosis: A Systematic Review.

A systematic review was conducted to provide an overview of the efficacy and safety of 125I irradiation stent placement for patients with hepatocellular carcinoma (HCC) and main portal vein tumor thrombosis (MPVTT). Six studies with 406 patients were included in the final analysis. The median overall survival for patients treated with 125I irradiation stent placement was 10.3months. The most common radiation-related adverse event was leukopenia. The stent-related adverse events consisted of fever, abdominal pain, hemorrhage, and anorexia. No stent or seed migration was reported. Overall, the use of an 125I irradiation stent has the potential to act as an alternative therapy for patients with HCC with MPVTT.

Safety and Efficacy of Radiotherapy Plus Sintilimab for HCC With Main Portal Vein Tumor Thrombosis

Safety and Efficacy of Radiotherapy Plus Sintilimab for HCC With Main Portal Vein Tumor Thrombosis

Efficacy and Prognosis of Radiotherapy for Hepatocellular Carcinoma with Tumor Thrombosis in Main Portal Vein or/and Vena Cava

To investigate response and survival of radiotherapy (RT) for hepatocellular carcinoma with tumor thrombosis in main portal vein or vena cava, and to analyze prognostic factors. From January 2010 to December 2016, a total of 61 cases of hepatocellular carcinoma with pathological or clinical diagnosis of hepatocellular carcinoma with tumor thrombosis in main portal vein or vena cava were enrolled this study. Main portal vein tumor thrombosis (PVTT) was defined as tumor thrombi was located in main trunk or first branches of portal vein. Fifty-five patients were with PVTT and 4 patients were with venous vein tumor thrombosis alone, respectively. In addition, another 2 patients were with both vein thromboses. All patients had a liver function of Child-Pugh A before radiotherapy. Eighty-five percent of patients (52/61) had a history of hepatitis B, 2% (2/61) had hepatitis C, and 12% (7/61) had no history of hepatitis. Eighty-four percent of patients (51/61) had previously received transcatheter arterial chemoembolization (TACE). Eight patients were treated with concurrent RT and sorafenib. Tumor response was evaluated in one to three months after completion of RT. Survival and prognostic factors were analyzed by Kaplan-Meier method and Cox regression model. The factors included gender, age, history of hepatitis, AFP level before radiotherapy, number of intrahepatic lesions, maximum tumor diameter (MTD), combined TACE, radiotherapy dose were included in analysis of prognosis. All patients were treated with intensity modulated radiotherapy by conventional fraction of 2Gy/f. The median dose was 50Gy (28-66Gy). Response rate (RR, complete response + partial response) was 55.7% when considering all lesions of whole body. In field of RT, RR of the primary tumor was 77.1% and RR of the tumor thrombosis was 83.7%. The 2-year overall survival was 29.9% and median survival time (MST) was 13.6 months. Median time to progression (TTP) was 4.7 months. The 2-year progression free survival of tumor thrombosis was 88.6%. Multivariate analysis showed that the MTD>10cm was an independent poor prognostic factor of TTP (HR, 1.961, 95%CI, 1.034-3.717). TTP in patients with MTD≤10cm and MTD>10cm were 5.0 months and 3.3 months (p=0.026), respectively. However, for MST, combination of TACE (both before or after RT) was an independent favor prognostic factor (HR, 0.184, 95%CI, 0.06-0.565). MST of combination therapy was 15 months, and MST of patients receiving radiotherapy alone was 4 months (p<0.001). Of all patients, grade III or higher liver function damage was 1.6%, and no lethal radiation-induced liver disease occurred. Grade III or higher hematological toxicity was 11.5%. The tumor thrombosis is more sensitive to radiation therapy than the primary tumor. Radiotherapy improves survival by the perfect control of tumor thrombosis. Progression of outside field of RT is primary failure mode for patients with main PVTT. Combination of radiotherapy and TACE is benefit to survivals.

Prognosticators of hepatocellular carcinoma with intrahepatic vascular invasion.

Objective:The prognosis of intrahepatic vascular invasion, including unilateral or main portal vein tumor thrombosis (PVTT) and hepatic vein thrombosis, is still poor. Many patients with intrahepatic vascular invasions never receive radiotherapy (RT). In recent years, more conformal RT techniques such as intensity-modulated RT (IMRT) have been developed and applied to treat other cancers and have significantly improved treatment results and decreased side effects. The purpose of this study is to evaluate the treatment results in patients with intrahepatic vascular invasion and explore the role of IMRT in these treatments.Materials and Methods:There were a total of 73 patients with newly diagnosed AJCC stage IIIB hepatocellular carcinoma (HCC), with either PVTT or hepatic vein tumor thrombosis between 2007 and 2015 in our hospital. IMRT was used for all patients who received RT. Prognostic factors, including treatment modalities, liver function, and comorbidities, were analyzed using univariate and multivariate analysis with the Cox model. Survival time was analyzed using the Kaplan–Meier method.Results:The longest follow-up time was 45.3 months. The median age was 67 years. Univariate analyses indicated that IMRT, transarterial chemoembolization (TACE), target therapy (sorafenib), tumor size, Child-Pugh class, and ascites were significantly associated with overall survival (OS). In multivariate analysis, IMRT (hazard ratio [HR], 0.495; P = 0.019), sorafenib (HR, 0.340; P = 0.013), tumor size (HR, 2.085; P = 0.020), and Child-Pugh class (P = 0.004), were independent prognostic predictors for patients with intrahepatic vessel invasion, but TACE and ascites were not. The outcomes of patients who had different treatment modalities were significantly different (P < 0.001). Patients who received IMRT with TACE had the best outcomes. Patients who received an RT dose above 5400 cGy had better outcomes than those who with a dose below 5400 cGy, although the results were not significantly different (P = 0.248).Conclusion:IMRT is an important treatment component for patients with intrahepatic vascular invasion. Combined treatment modalities, such as IMRT with TACE, could improve the outcomes of HCC patients with intrahepatic vessel invasion.

주요간문맥종양혈전을 동반한 간세포암에 대한 다기관 체부정위방사선치료계획 비교연구(KROG 16-17)

Background/Aims: To evaluate the technical feasibility of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) with the major portal vein tumor thrombosis (PVTT). Methods: Ten institutions affiliated with the Korean Stereotactic Radiosurgery Group were provided the contours of four cases: the first case was the first branch PVTT with sufficient normal liver volume (NLV), the second was the first branch PVTT with insufficient NLV, the third was the main trunk PVTT at confluence level, and the fourth was the main trunk PVTT with entire length. The institutions were asked to make SBRT plans according to their current treatment protocols and to complete facility questionnaires. Results: Based on institutional protocols, SBRT was feasible in nine institutions for the first case (32-60 Gy in 3-5 fractions), in eight institutions for the second case (32-50 Gy in 3-5 fractions), in seven institutions for the third case (35-60 Gy in 3-5 fractions), and in four institutions for the fourth case (35-42 Gy in 4-5 fractions). The other institutions recommended hypo- or conventional fractionation due to insufficient NLV or gastrointestinal organ proximity. With analysis of the SBRT dose to the central hepatobiliary tract, the major PVTT could theoretically be associated with a high risk of hepatobiliary toxicity. Conclusions: Although SBRT is a technically feasible option for HCC with the major PVTT, there was a variability among the participating institutions. Therefore, further studies will be necessary to standardize the practice of SBRT for the major PVTT. (J Liver Cancer 2018;18:130-141)

Survival and prognostic factors for patients with advanced hepatocellular carcinoma after stereotactic ablative radiotherapy.

ObjectiveTo evaluate the survival outcomes and prognostic factors of patients with advanced hepatocellular carcinoma (HCC) who underwent stereotactic ablative radiotherapy (SABR).MethodsThis retrospective study evaluated patients with advanced HCC who underwent SABR between December 2007 and July 2015. All patients had Barcelona Clinic Liver Cancer stage C disease and Child–Turcotte–Pugh (CTP) class A–B function. In-field control (IFC), overall survival (OS), prognostic factors, and toxicity were evaluated.ResultsIn this study of 89 patients, the 3-year IFC rate was 78.1%, and the 1-year and 3-year OS rates were 45.9% and 24.3%, respectively. The multivariate analysis revealed that CTP class, the presence of main portal vein tumor thrombosis, and the presence of extrahepatic spread were independent predictors of OS. The expected median OS values among patients with ≥2, 1, and 0 predictors were 4.2, 8.6, and 26.4 months, respectively (p <0.001).ConclusionsSABR may be useful for patients with advanced HCC, and patient selection could be based on the CTP classification, main portal vein tumor thrombosis, and extrahepatic spread.

Survival outcomes of hepatic resection compared with transarterial chemoembolization or sorafenib for hepatocellular carcinoma with portal vein tumor thrombosis.

Background/Aims:Treating hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) remains controversial. We compared the outcomes of hepatic resection (HR), transarterial chemoembolization (TACE), and sorafenib therapy as treatments for HCC with PVTT.Methods:Patients diagnosed as HCC with PVTT between January 2000 and December 2011 who received treatment with sorafenib, HR, or TACE were included. Patients with main PVTT, superior mesenteric vein tumor thrombosis, or Child-Turcotte-Pugh (CTP) class C were excluded. The records of 172 patients were analyzed retrospectively. HR, TACE, and sorafenib treatment were performed is 40, 80, and 52 patients respectively. PVTT was classified as either involving the segmental branch (type I) or extending to involve the right or left portal vein (type II).Results:The median survival time was significantly longer in the HR group (19.9 months) than in the TACE and sorafenib groups (6.6 and 6.2 months, respectively; both p<0.001), and did not differ significantly between the latter two groups (p=0.698). Among patients with CTP class A, type I PVTT or unilobar-involved HCC, the median survival time was longer in the HR group than in the TACE and sorafenib groups (p=0.006). In univariate analyses, the initial treatment method, tumor size, PVTT type, involved lobe, CTP class, and presence of cirrhosis or ascites were correlated with overall survival. The significant prognostic factors for overall survival in Cox proportional-hazards regression analysis were initial treatment method (HR vs. TACE: hazard ratio=1.750, p=0.036; HR vs. sorafenib: hazard ratio=2.262, p=0.006), involved lobe (hazard ratio=1.705, p=0.008), PVTT type (hazard ratio=1.617, p=0.013), and CTP class (hazard ratio=1.712, p=0.012).Conclusions:Compared with TACE or sorafenib, HR may prolong the survival of patients with HCC in cases of CTP class A, type I PVTT or unilobar-involved HCC.

A systematic review on the safety and effectiveness of yttrium-90 radioembolization for hepatocellular carcinoma with portal vein tumor thrombosis

Background/Aim:Over the past two decades, several advances have been made in the management of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT). Yttrium-90 (90Y) radioembolization has recently been made a treatment option for patients with HCC and PVTT. However, there is still a need to systematicly evaluate the outcomes of 90Y radioembolization for HCC and PVTT. We aimed to assess the safety and effectiveness of 90Y radioembolization for HCC and PVTT. We performed a systematic review of clinical trials, clinical studies, and abstracts from conferences that qualified for analysis.Materials and Methods:PubMed, EMBASE, Cochrane Database of Systematic Review, CINAHL, and the “gray” literature (Google Scholar) were searched for all reports (1991-2016) related to 90Y radioembolization for HCC and PVTT.Results:A total of 14 clinical studies and three abstracts from conferences including 722 patients qualified for the analysis. The median length of follow-up was 7.2 months; the median time to progression was 5.6 months, and median disease control rate was 74.3%. Radiological response data were reported in five studies, and the median reported value of patients with complete response, partial response, stable disease, and progressive disease were 3.2%, 16.5%, 31.3%, and 28%, respectively. The median survival was 9.7 months for all patients, including the median overall survival (OS) were 12.1, 6.1 months of Child-Pugh class A and B patients, and the median OS were 6.1, 13.4 months of main and branch PVTT patients, respectively. The common toxicities were fatigue, nausea/vomiting, abdominal pain, mostly not requiring medical intervention needed no medication intervention.Conclusions:90Y radioembolization is a safe and effective treatment for HCC and PVTT.

Effectiveness and safety of proton beam therapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis

To evaluate the clinical effectiveness and safety of proton beam therapy (PBT) in advanced hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT). Twenty-seven HCC patients with PVTT underwent PBT, including 22 patients with modified International Union Against Cancer (mUICC) stage IVA,five patients with stage IVB primary tumors, and 16 with main PVTT. A median dose of 55 GyE (range, 50-66 GyE) in 20-22 fractions was delivered to a target volume encompassing both the PVTT and primary tumor. Overall, treatment was well tolerated, with no toxicity of grade ≥ 3. Median overall survival (OS) times in all patients and in stage IVA patients were 13.2 months and 16 months, respectively. Assessments of PVTT response showed complete response in 0 of 27 (0%) patients, partial response in 15 (55.6%), stable disease in 10 (37%), and progressive disease in 2 (7.4%) patients, with an objective response rate of 55.6%. PVTT responders showed significantly higher actuarial 1-year local progression-free survival (LPFS; 85.6% vs. 51.3%), relapse-free survival (RFS; 20% vs. 0%) and OS (80% vs. 25%) rates than nonresponders (p<0.05 each). Multivariate analysis showed that PVTT response and mUICC stage were independent prognostic factors for OS. Our data suggest that PBT could improve LPFS, RFS, and OS in advanced HCC patients with PVTT and it is feasible and safe for these patients.

Three-dimensional conformal radiotherapy for portal vein tumor thrombosis alone in advanced hepatocellular carcinoma.

PurposeWe sought to evaluate the clinical outcomes of 3-dimensional conformal radiation therapy (3D-CRT) for portal vein tumor thrombosis (PVTT) alone in patients with advanced hepatocellular carcinoma.Materials and MethodsWe retrospectively analyzed data on 46 patients who received 3D-CRT for PVTT alone between June 2002 and December 2011. Response was evaluated following the Response Evaluation Criteria in Solid Tumors. Prognostic factors and 1-year survival rates were compared between responders and non-responders.ResultsThirty-seven patients (80.4%) had category B Child-Pugh scores. The Eastern Cooperative Oncology Group performance status score was 2 in 20 patients. Thirty patients (65.2%) had main or bilateral PVTT. The median irradiation dose was 50 Gy (range, 35 to 60 Gy) and the daily median dose was 2 Gy (range, 2.0 to 2.5 Gy). PVTT response was classified as complete response in 3 patients (6.5%), partial response in 12 (26.1%), stable disease in 19 (41.3%), and progressive disease in 12 (26.1%). There were 2 cases of grade 3 toxicities during or 3 months after radiotherapy. Twelve patients in the responder group (15 patients) received at least 50 Gy irradiation, but about 84% of patients in the non-responder group received less than 50 Gy. The 1-year survival rate was 66.8% in responders and 27.4% in non-responders constituting a statistically significant difference (p = 0.008).ConclusionConformal radiotherapy for PVTT alone could be chosen as a palliative treatment modality in patients with unfavorable conditions (liver, patient, or tumor factors). However, more than 50 Gy of radiation may be required.

Radiotherapy Plus Transarterial Chemoembolization for Hepatocellular Carcinoma Invading the Portal Vein: Long-Term Patient Outcomes

We have evaluated the clinical outcomes of patients after transarterial chemoembolization (TACE) and 3-dimensional conformal radiotherapy for hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). A registry database of 412 patients treated with TACE and three-dimensional conformal radiotherapy for HCC with PVTT between August 2002 and August 2008 were analyzed retrospectively. The radiotherapy volume included the PVTT, with a 2- to 3-cm margin to cover adjacent HCC. Intrahepatic primary HCC was managed by TACE before or after radiotherapy. Median patient age was 52 years old, and 88.1% of patients were male. Main or bilateral PVTT was observed in 200 (48.5%) patients. Median radiation dose was 40 Gy (range, 21-60 Gy) delivered in 2- to 5-Gy fractions. We found that 3.6% of patients achieved a complete response and that 24.3% of patients achieved a partial response. The response and progression-free rates of PVTT were 39.6% and 85.6%, respectively. Median patient survival was 10.6 months, and the 1- and 2-year survival rates were 42.5% and 22.8%, respectively. Significant independent variables associated with overall survival included advanced tumor stage, alpha-fetoprotein level, degree of PVTT, and response to radiotherapy. Forty-one patients (10.0%) showed grade 3-4 hepatic toxicity during or 3 months after completion of radiotherapy. Grades 2-3 gastroduodenal complications were observed in 15 patients (3.6%). Radiotherapy is a safe and effective treatment for PVTT in patients with HCC. These results suggested that the combination of TACE and radiotherapy is a treatment option for relieving and/or stabilizing PVTT in patients with advanced HCC.

Prognostic Index for Portal Vein Tumor Thrombosis in Patients with Hepatocellular Carcinoma Treated with Radiation Therapy

We performed a retrospective review of 281 hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) treated with radiation therapy (RT) between 1998 and 2008 to develop a prognostic model for those patients. Of the 281 patients, PVTT and intrahepatic main masses completely disappeared in 10 patients (3.6%), and shown a partial response in 141 patients (50.2%). The median survival was 11.6 months. Patients who had more than PR have shown significantly longer survival than the others (22.0 months vs 5.0 months, P < 0.001). On the multivariate analysis, pre-treatment poor prognosticators for overall survival were ECOG performance status, Child-Pugh class, multiple tumors, main PVTT, complete portal vein occlusion, lymph node metastasis, and primary tumor size. Prognostic index of RT for PVTT of HCC (PITH) scores were defined as the number of pre-treatment poor prognostic factors. PITH scores correlated well with overall survival. In the analysis of 1 and 2 yr overall survival rate, patients who had PITH scores of 3 or greater showed a significantly lower rate of overall survival than the others (33.0%, 17.3% vs 70.1%, 40.8%, respectively, P < 0.001). The PITH scoring model, proposed in the current study in HCC patients with PVTT, reliably predict overall survival.

Pathological Complete Remission of Advanced Hepatocellular Carcinoma with Main Portal Vein Tumor Thrombosis by Hepatic Arterial Infusion Chemotherapy

Cures for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) are rare and difficult. We report a case of pathologically confirmed complete remission of HCC induced by hepatic arterial infusion chemotherapy (HAIC). A 45-year-old male patient had a massive HCC in the right lobe of the liver and tumor thrombus in the right and main portal veins. He achieved a partial response after two cycles of HAIC with 5-fluorouracil (750 mg/m(2)) and cisplatin (25 mg/m(2)). After the completion of six cycles he received a curative partial hepatectomy, and histopathology revealed complete necrosis without any viable tumor cell. He was in good health at a 4-month follow-up. These results suggest that this regimen is a promising therapeutic modality for the treatment of advanced HCC with PVTT.