Effective treatment strategies other than sorafenib for the patients with advanced hepatocellular carcinoma invading portal vein

Patients with hepatocellular carcinoma(HCC) accompanying portal vein tumor thrombosis(PVTT) have relatively few therapeutic options and an extremely poor prognosis. These patients are classified into barcelonaclinic liver cancer stage C and sorafenib is suggested as the standard therapy of care. However, overall survival(OS) gain from sorafenib is unsatisfactory and better treatment modalities are urgently required. Therefore, we critically appraised recent data for the various treatment strategies for patients with HCC accompanying PVTT. In suitable patients, even surgical resection can be considered a potentially curative strategy. Transarterial chemoembolization(TACE) can be performed effectively and safely in a carefully chosen population of patients with reserved liver function and sufficient collateral blood flow nearby the blocked portal vein. A recent metaanalysis demonstrated that TACE achieved a substantial improvement of OS in HCC patients accompanying PVTT compared with best supportive care. In addition, transarterial radioembolization(TARE) using yttrium-90 microspheres achieves quality-of-life advantages and is as effective as TACE. A large proportion of HCC patients accompanying PVTT are considered to be proper for TARE. Moreover, TACE or TARE achieved comparable outcomes to sorafenib in recent studies and it was also reported that the combination of radiotherapy with TACE achieved a survival gain compared to sorafenib in HCC patients accompanying PVTT. Surgical resectionbased multimodal treatments, transarterial approaches including TACE and TARE, and TACE-based appropriate combination strategies may improve OS of HCC patients accompanying PVTT.     

Comparative effectiveness of traditional chemoembolization with or without sorafenib for hepatocellular carcinoma

AIM: To compare the overall survival (OS) and progression-free survival (PFS) with associated adverse events (AE) in patients with unresectable hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) + sorafenib vs TACE alone. METHODS: In this retrospective cohort study we collected data on all consecutive patients with a diagnosis of unresectable HCC between 2007 and 2011 who had been treated with TACE + sorafenib or TACE alone. We hypothesized that the combination therapy is superior to TACE alone in improving the survival in these patients. Data extracted included patient’s demographics, etiology of liver disease, histology of HCC, stage of liver disease with respect to model of end stage liverdisease score and Child-Turcotte-Pugh (CTP) classification and Barcelona Clinic Liver Cancer (BCLC) staging for HCC. Computed tomography scan findings, alpha fetoprotein levels, number of treatments and related AE were also recorded and analyzed. RESULTS: Of the 43 patients who met inclusion criteria, 13 were treated with TACE + sorafenib and 30 with TACE alone. There was no significant difference in median survival: 20.6 mo (95%CI: 13.4-38.4) for the TACE + sorafenib and 18.3 mo (95%CI: 11.8-32.9) for the TACE alone (P = 0.72). There were also no statistically significant differences between groups in OS (HR = 0.82, 95%CI: 0.38-1.77; P = 0.61), PFS (HR = 0.93, 95%CI: 0.45-1.89; P = 0.83), and treatment-related toxicities (P = 0.554). CTP classification and BCLC staging for HCC were statistically significant (P = 0.001, P = 0.04 respectively) in predicting the survival in patients with HCC. The common AE observed were abdominal pain, nausea, vomiting and mild elevation of liver enzymes. CONCLUSION: Combination therapy with TACE + sorafenib is safe and equally effective as TACE alone in patients with unresectable HCC. CTP classification and BCLC staging were the significant predictors of survival. Future trials with large number of patients are needed to further validate this observation.     

Transarterial chemoembolization in hepatocellular carcinoma treatment: Barcelona clinic liver cancer staging system

Hepatocellular carcinoma(HCC),the fifth most common cancer that predominantly occurs in liver cirrhosis patients,requires staging systems to design treatments. The barcelona clinic liver cancer staging system(BCLC) is the most commonly used HCC management guideline. For BCLC stage B(intermediate HCC),transarterial chemoembolization(TACE) is the standard treatment. Many studies support the use of TACE in early and advanced HCC patients. For BCLC stage 0(very early HCC),TACE could be an alternative for patients unsuitable for radiofrequency ablation(RFA) or hepatic resection. In patients with BCLC stage A,TACE plus RFA provides better local tumor control than RFA alone. TACE can serve as bridge therapy for patients awaiting liver transplantation. For patients with BCLC B,TACE provides survival benefits compared with supportive care options. However,because of the substantial heterogeneity in the patient population with this stage,a better patient stratification system is needed to select the best candidates for TACE. Sorafenib represents the first line treatment in patients with BCLC C stage HCC. Sorafenib plus TACE has shown a demonstrable effect in delaying tumor progression. Additionally,TACE plus radiotherapy has yielded better survival in patients with HCC and portal venous thrombosis. Considering these observations together,TACE clearly has a critical role in the treatment of HCC as a stand-alone or combination therapy in each stage of HCC. Diverse treatment modalities should be used for patients with HCC and a better patient stratification system should be developed to select the best candidates for TACE.     

Management of hepatocellular carcinoma patients with portal vein tumor thrombosis: A narrative review

Background: Hepatocellular carcinoma(HCC) is one of the main reasons for malignancy-related death. Portal vein tumor thrombosis(PVTT) is the most common form of macrovascular invasion related to HCC occurring in 10%-60% of patients. HCC with PVTT is usually characterized by worsening liver function, vulnerability to blood metastasis, higher incidence of complications associated with portal hypertension, and intolerance to treatment when compared with that without PVTT. If only treated with suppo...     

Current systemic treatment of hepatocellular carcinoma: A review of the literature

Hepatocellular carcinoma (HCC) is the fifth most common form of human cancer worldwide and the third most common cause of cancer-related deaths. The strategies of various treatments for HCC depend on the stage of tumor, the status of patient’s performance and the reserved hepatic function. The Barcelona Clinic Liver Cancer (BCLC) staging system is currently used most for patients with HCC. For example, for patients with BCLC stage 0 (very early stage) and stage A (early stage) HCC, the curable treatment modalities, including resection, transplantation and radiofrequency ablation, are taken into consideration. If the patients are in BCLC stage B (intermediate stage) and stage C (advanced stage) HCC, they may need the palliative transarterial chemoembolization and even the target medication of sorafenib. In addition, symptomatic treatment is always recommended for patients with BCLC stage D (end stage) HCC. In this review, we will attempt to summarize the historical perspective and the current developments of systemic therapies in BCLC stage B and C in HCC.     

Surgical treatment for advanced hepatocellular carcinoma with portal vein tumor thrombus

The Barcelona Clinic Liver Cancer staging system recommends a tyrosine kinase inhibitor (sorafenib) as standard therapy in advanced hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). Sorafenib has been shown to prolong median overall survival (OS) by approximately 3 months in advanced HCC patients with PVTT (8.1 vs. 4.9 months). However, its clinical effectiveness is still controversial and standard treatment with sorafenib is not established in Japan. Surgical resection is considered a potentially curative treatment and provides an acceptable outcome for carefully selected patients. The surgical mortality rate in patients with PVTT who receive surgical resection ranges from 0% to 10%. The median survival time and 1-year OS rate in HCC patients with PVTT who undergo surgical resection have been found to range from 8 to 22 months and 21.7% to 69.6%, respectively. But improvement in therapeutic outcome is difficult with surgical treatment alone. Combination treatment in conjunction with such methods as transarterial chemoembolization, hepatic artery infusion chemotherapy, and radiotherapy has been found to improve the prognosis (median survival time, 11.5–37 months; 1-year OS rate, 46.8–100%). Yet, many problems remain, such as surgical indications and surgical techniques. After resolving these points, a multidisciplinary strategy based on surgical treatment should be established for advanced HCC with PVTT.     

Early prediction of survival in hepatocellular carcinoma patients treated with transarterial chemoembolization plus sorafenib

AIM To identify clinical biomarkers that could early predict improved survival in patients with advanced-stage hepatocellular carcinoma(HCC) treated with transarterial chemoembolization combined with sorafenib(TACE-S).METHODS We retrospectively evaluated the medical records of consecutive patients with advanced-stage HCC who underwent TACE-S from January 2012 to December 2015. At the first follow-up 4-6 wk after TACE-S(median, 38 d; range, 33-45 d), patients exhibiting the modified Response Evaluation Criteria in Solid Tumors(m RECIST)-evaluated complete response, partial response, and stable disease were categorized as early disease control. At this time point, multiple variables were analyzed to identify the related factors affecting survival.RESULTS Ninety-five patients were included in this study, and 60 of these patients achieved early disease control, with an overall disease control rate(DCR) of 63.2%. Patients who got sorafenib at the first TACE(no previous TACE) and patients without portal vein tumor thrombus(PVTT) had a higher DCR than those who underwent previous TACE before TACE-S(72.4% vs 48.6%, P = 0.019) and those with PVTT(75.5% vs 50.0%, P = 0.010). Early disease control after TACE-S, no previous TACE, and no PVTT were the independent prognostic factors for survival in the uni-and multivariate analyses.CONCLUSION The first follow-up 4-6 wk after TACE-S can be used as the earliest time point to assess the response to TACE-S, and patients with m RECIST-evaluated early disease control, no previous TACE, and no PVTT had better survival.     

Radiotherapy as valid modality for hepatocellular carcinoma with portal vein tumor thrombosis

Although the current standard treatment for hepatocellular carcinoma(HCC) with portal vein tumor thrombosis(PVTT) is sorafenib, many previous studies have established the need for a reliable local modality for PVTT control, which is a major cause of liver function deterioration and metastasis. Additionally, there is growing evidence for the prognostic significance of PVTT classification according to the location of tumor thrombosis. Favorable outcomes can be obtained by applying local modalities, including surgery or transarterial chemoembolization, especially in second-order or distal branch PVTT. Rapid control of PVTT could maintain or improve liver function and reduce intrahepatic as well as distant metastasis. Radiotherapy(RT) is one of the main locoregional treatment modalities in oncologic fields, but has rarely been used in HCC because of concerns regarding hepatic toxicity. However, with the development of advanced techniques, RT has been increasingly applied in HCC management. Randomized studies have yet to definitively prove the benefit of RT, but several comparative studies have justified the application of RT in HCC. The value of RT is especially noticeable in HCC with PVTT; several prospective and retrospective studies have reported favorable outcomes, including a 40% to 60% objective response rate and median overall survival of 15 mo to 20 mo in responders. In this review, we evaluate the role of RT as an alternative local modality in HCC with PVTT.     

An evidence-based multidisciplinary approach to the management of hepatocellular carcinoma (HCC): the Alberta HCC algorithm

Hepatocellular carcinoma (HCC) is one of only a few malignancies with an increasing incidence in North America. Because the vast majority of HCCs occur in the setting of a cirrhotic liver, management of this malignancy is best performed in a multidisciplinary group that recognizes the importance of liver function, as well as patient and tumour characteristics. The Barcelona Clinic Liver Cancer (BCLC) staging system is preferred for HCC because it incorporates the tumour characteristics (ie, tumour-node-metastasis stage), the patient's performance status and liver function according to the Child-Turcotte-Pugh classification, and then links the BCLC stage to recommended therapeutic interventions. However, the BCLC algorithm does not recognize the potential role of radiofrequency ablation for very early stage HCC, the expanding role of liver transplantation in the management of HCC, the role of transarterial chemoembolization in single large tumours, the potential role of transarterial radioembolization with 90Yttrium and the limited evidence for using sorafenib in Child- Turcotte-Pugh class B cirrhotic patients. The current review article presents an evidence-based approach to the multidisciplinary management of HCC along with a new algorithm for the management of HCC that incorporates the BCLC staging system and the authors' local selection criteria for resection, ablative techniques, liver transplantation, transarterial chemoembolization, transarterial radioembolization and sorafenib in Alberta.     

Prognostic factors for survival after transarterial chemoembolization combined with microwave ablation for hepatocellular carcinoma

AIM: To analyze prognostic factors for survival after transarterial chemoembolization (TACE) combined with microwave ablation (MWA) for hepatocellular carcinoma (HCC).METHODS: Clinical data of 86 patients who underwent TACE combined with MWA between January 2006 and December 2013 were retrospectively analyzed in this study. Survival curves were detected using log-rank test. Univariate analysis was performed using log-rank test with respect to 13 prognostic factors affecting survival. All statistically significant prognostic factors identified by univariate analysis were entered into a Cox proportion hazards regression model to identify independent predictors of survival. P values were two-sided and P < 0.05 was considered statistically significant.RESULTS: Median follow-up time was 47.6 mo, and median survival time of enrolled patients was 21.5 mo. The 1-, 2-, 3- and 5-year overall survival rates were 72.1%, 44.1%, 31.4% and 13.9%, respectively. Tumor size(χ² = 14.999, P = 0.000), Barcelona Clinic Liver Cancer (BCLC) stage (χ² = 29.765, P = 0.000), Child-Pugh class (χ² = 51.820, P = 0.000), portal vein tumor thrombus (PVTT) (χ² = 43.086, P = 0.000), arterio-venous fistula (χ² = 29.791, P = 0.000), MWA therapy times (χ² = 12.920, P = 0.002), Eastern Cooperative Oncology Group (ECOG) score (χ² = 28.660, P = 0.000) and targeted drug usage (χ² = 10.901, P = 0.001) were found to be significantly associated with overall survival by univariate analysis. Multivariate analysis identified that tumor size (95%CI: 1.608-4.962, P = 0.000), BCLC stage (95%CI: 1.016-2.208, P = 0.020), PVTT (95%CI: 2.062-9.068, P = 0.000), MWA therapy times (95%CI: 0.402-0.745, P = 0.000), ECOG score (95%CI: 1.012-3.053, P = 0.045) and targeted drug usage (95%CI: 1.335-3.143, P = 0.001) were independent prognostic factors associated with overall survival.CONCLUSION: Superior performance status, MWA treatment and targeted drug were favorable factors, and large HCC, PVTT and advanced BCLC stage were risk factors for survival after TACE-MWA for HCC.     

Complete response with sorafenib and transcatheter arterial chemoembolization in unresectable hepatocellular carcinoma

Patients with advanced hepatocellular carcinoma(HCC) showing portal vein tumor thrombosis(PVTT) have an extremely poor prognosis. According to treatment guidelines, the only option for HCC patients with PVTT is sorafenib chemotherapy. However, in Asia, various treatments have been attempted and possible prolongation of overall survival has been repeatedly reported. We herein report the first case of a patient with an initially unresectable advanced HCC with PVTT who underwent curative hepatectomy after sorafenib and transcatheter arterial chemoembolization(TACE) showing complete histological response. Two months after induction with sorafenib, a significant decrease in serum alpha-fetoprotein level was observed and computed tomography imaging showed a significant decrease in tumor size. Because of remaining PVTT, TACE and curative resection were performed. The combination of sorafenib and TACE may be an effective treatment for HCC patients with PVTT.     

Prognostic factors of spontaneously ruptured hepatocellular carcinoma

AIM: To evaluate the prognostic factors in patients with spontaneously ruptured hepatocellular carcinoma (HCC).METHODS: Seventy-nine patients experiencing spontaneous rupture of HCC between April 2004 and August 2014 were enrolled in this study. The clinical features, treatment modalities and outcomes were reviewed. The statistical methods used in this work included univariate analysis, Kaplan-Meier survival analysis with log-rank tests, and multivariate analysis using a Cox regression hazard model.RESULTS: Of the 79 patients with HCC rupture, 17 (21.5%) underwent surgery, 32 (40.5%) underwent transarterial embolization (TAE), and 30 (38%) received conservative treatment. The median survival time was 125 d, and the mortality rate at 30 d was 27.8%. Multivariate analysis revealed that lesion length (HR = 1.46, P < 0.001), lesion number (HR = 1.37, P = 0.042), treatment before tumor rupture (HR = 4.36, P = 0.019), alanine transaminase levels (HR = 1.0, P = 0.011), bicarbonate levels (HR = 1.18, P < 0.001), age (HR = 0.96, P = 0.026), anti-tumor therapy during the follow-up period (HR = 0.21, P = 0.008), and albumin levels (HR = 0.89, P = 0.010) were independent prognostic factors of survival after HCC rupture. The Barcelona-Clinic Liver Cancer (BCLC) stage was also an important prognostic factor; the median survival times for BCLC stages A, B and C were 251, 175 and 40 d, respectively (P < 0.001).CONCLUSION: Anti-tumor therapy during the follow-up period, without a history of anti-tumor therapy prior to HCC rupture, small tumor length and number, and early BCLC stage are the most crucial predictors associated with satisfactory overall survival. Other factors play only a small role in overall survival.     

Survival rates according to barcelona clinic liver cancer sub-staging system after transarterial embolization for intermediate hepatocellular carcinoma

AIM: To investigate the survival rates after transarterial embolization(TAE).METHODS: One hundred third six hepatocellular carcinoma(HCC) patients [90 barcelona clinic liver cancer(BCLC) B] were submitted to TAE between August 2008 and December 2013 in a single center were retrospectively studied. TAE was performed via superselective catheterization followed by embolization with polyvinyl alcohol or microspheres. The date of the first embolization until death or the last follow-up date was used for the assessment of survival. The survival rates were calculated using the Kaplan-Meier method, and the groups were compared using the log-rank test.RESULTS: The overall mean survival was 35.8 mo(95%CI: 25.1-52.0). The survival rates of the BCLC A patients(33.7%) were 98.9%, 79.0% and 58.0% at 12, 24 and 36 mo, respectively, and the mean survival was 38.1 mo(95%CI: 27.5-52.0). The survival rates of the BCLC B patients(66.2%) were 89.0%, 69.0% and 49.5% at 12, 24 and 36 mo, respectively, and the mean survival was 29.0 mo(95%CI: 17.2-34). The survival rates according to the BCLC B sub-staging showed significant differences between the groups, with mean survival rates in the B1, B2, B3 and B4 groups of 33.5 mo(95%CI: 32.8-34.3), 28.6 mo(95%CI: 27.5-29.8), 19.0 mo(95%CI: 17.2-20.9) and 13 mo, respectively(P = 0.013).CONCLUSION : The BCLC sub-stagingsystem could add additional prognosis information for postembolization survival rates in HCC patients.     

Medical treatments: in association or alone, their roles and their future perspectives

Management of hepatocellular carcinoma (HCC) is a complex issue, as it needs to take into account the liver disease, the cancer stage and the performance status of the patient. The treatment decision has to be based on robust scientific evidence and for this it is instrumental to have a proper staging system linked to the treatment indication. The BCLC proposal serves these two purposes and has been validated worldwide and endorsed by several scientific associations. The sole systemic therapy that has shown efficacy in improving the survival of HCC patients is sorafenib, an oral kinase inhibitor that blocks the Raf/MEK/ERK pathway and the receptor for VEGFR 2 and PDGFR-beta. Sorafenib has been recognized as the standard of care for patients who cannot benefit from treatments of higher priority and established efficacy, such as surgical resection, transplantation, ablation and transarterial chemoembolization. Sorafenib has changed the management of HCC, opening the path to combination therapies for patients at advanced stages and to evaluation as an adjuvant for those in earlier evolutionary stages.     

Combination of TACE and Sorafenib Improves Outcomes in BCLC Stages B/C of Hepatocellular Carcinoma: A Single Centre Experience

Background & Aim. Transarterial chemoembolization (TACE) or sorafenib is recommended for hepatocellular carcinoma BCLC stages B and C respectively. We studied the role of combination of TACE and sorafenib in BCLC stages B/C.Material and methods. We undertook an observational study on a cohort of cirrhotics with HCC from August 2010 through October 2014. Patients in BCLC stages B/C who had received TACE and/or sorafenib were included. mRECIST criteria were used to assess tumor response. The primary end point was overall survival.Results. Out of 124 patients, 47.6% were in BCLC-B and 52.4% in BCLC-C. Baseline characteristics were comparable. The predominant etiology was cryptogenic (37.2% and 38.5%, p = NS). 49.1% in BCLC-B and 56.9% in BCLC-C had received TACE+sorafenib. In BCLC-B, the overall survival improved from 9 months (95% CI 6.3-11.7) using TACE only to 16 months (95% CI 12.9-19.1) using TACE+sorafenib (p < 0.05). In BCLC-C, addition of TACE to sorafenib improved the overall survival from 4 months (95%CI 3-5) to 9 months (95%CI 6.8-11.2) (p < 0.0001). As per mRECIST criteria, patients on TACE+sorafenib had reduced progressive disease (37.8% vs. 83.3%), improved partial response (43.2% vs. 3.3%) and one had complete response compared to those on sorafenib alone (p < 0.0001) in BCLC-C but not in BCLC-B group. Hand foot syndrome was noted in 27.7% patients on sorafenib and post TACE syndrome in 80.2% patients, but both were reversible. No major adverse events were noted.Conclusion. TACE+sorafenib was more effective than TACE or sorafenib alone in HCC BCLC stages B or C with a significant survival benefit and improved tumour regression especially in BCLC-C patients.     

Efficacy comparison of optimal treatments for hepatocellular carcinoma patients with portal vein tumor thrombus

Introduction and objectivesOptimal treatment of hepatocellular carcinoma (HCC) involving portal vein tumor thrombus (PVTT) remains controversial.Materials and methodsA total of 627 HCC patients with PVTT after initial treatment with one of the following at Affiliated Tumor Hospital of Guangxi Medical University: liver resection (LR, n = 225), transarterial chemoembolization (TACE, n = 298) or sorafenib (n = 104) were recruited and randomly divided into the training cohort (n = 314) and internal validation cohort (n = 313). Survival analysis were repeated after stratifying patients by Cheng PVTT type.ResultsResection led to significantly higher OS than the other two treatments among patients with type I or II PVTT. TACE worked significantly better than the other two treatments for patients with type III. All three treatments were associated with similar OS among patients with type IV. These findings were supported by the internal validation cohort.ConclusionsOur results suggest that the optimal treatment for HCC involving PVTT depends on the type of PVTT. LR may be more appropriate for type I or II PVTT; TACE, for type III Sorafenib may be more appropriate than invasive treatments for patients with type IV PVTT.     

Appropriate treatment strategies improve survival of hepatocellular carcinoma patients with portal vein tumor thrombus

AIM:To evaluate the survival benefits of different treatment strategies for hepatocellular carcinoma(HCC)patients with portal vein tumor thrombus(PVTT)and to determine the prognosis factors.METHODS:Between 2007 and 2009,338 HCC patients treated for PVTT were retrospectively studied.The patients were divided into 4 groups that underwent different treatments:the conservative treatment group(n=75),the transarterial chemoembolization(TACE)group(n=86),the hepatic resection group(n=90),and the hepatic resection associated with postoperative TACE group(n=87).Survival rates were determined using the Kaplan-Meier method and differences between the groups were identified through log-rankanalysis.Cox’s proportional hazard model was used to identify the risk factors for survival.RESULTS:The mean survival periods for patients in the conservative treatment,TACE,hepatic resection and hepatic resection associated with postoperative TACE groups were 3.8,7,8.2 and 15.1 mo,respectively.Significant differences were observed in the survival rates.For the surgical resection associated with postoperative TACE group,the survival rates after 1,2 and3 years were 49%,37%and 19%,respectively.These results were significantly higher than those of the other groups(P<0.05).Meanwhile,the 1,2 and 3 year survival rates for the surgical resection group were 28%,20%and 15%,whereas those for the TACE group were17.5%,0%and 0%,respectively.These values significantly increased after hepatic resection compared with those after TACE(P<0.05).CONCLUSION:Surgical resection is the most effective therapeutic strategy for HCC patients with PVTT and results in high hepatic functional reserve.For patients who can tolerate the procedure,postoperative TACE is necessary to prevent recurrence and prolong the survival period.     

Adjuvant sorafenib after heptectomy for Barcelona Clinic Liver Cancer-stage C hepatocellular carcinoma patients

AIM: To investigate the efficacy and safety of adjuvant sorafenib after curative resection for patients with Barcelona Clinic Liver Cancer (BCLC)-stage C hepatocellular carcinoma (HCC).METHODS: Thirty-four HCC patients, classified as BCLC-stage C, received adjuvant sorafenib for high-risk of tumor recurrence after curative hepatectomy at a tertiary care university hospital. The study group was compared with a case-matched control group of 68 patients who received curative hepatectomy for HCC during the study period in a 1:2 ratio.RESULTS: The tumor recurrence rate was markedly lower in the sorafenib group (15/34, 44.1%) than in the control group (51/68, 75%, P = 0.002). The median disease-free survival was 12 mo in the study group and 10 mo in the control group. Tumor number more than 3, macrovascular invasion, hilar lymph nodes metastasis, and treatment with sorafenib were significant factors of disease-free survival by univariate analysis. Tumor number more than 3 and treatment with sorafenib were significant risk factors of disease-free survival by multivariate analysis in the Cox proportional hazards model. The disease-free survival and cumulative overall survival in the study group were significantly better than in the control group (P = 0.034 and 0.016, respectively).CONCLUSION: Our study verifies the potential benefit and safety of adjuvant sorafenib for both decreasing HCC recurrence and extending disease-free and overall survival rates for patients with BCLC-stage C HCC after curative resection.     

Practical Effect of Sorafenib Monotherapy on Advanced Hepatocellular Carcinoma and Portal Vein Tumor Thrombosis

Background/Aims

We investigated the effects of sorafenib monotherapy on advanced hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) in a clinical setting.

Methods

In total, 143 consecutive patients with unresectable HCC were treated with sorafenib. Among these patients, 30 patients with advanced HCC and PVTT (Vp3 or 4) were treated with sorafenib monotherapy.

Results

All patients had a performance status of 1 to 2 (Eastern Cooperative Oncology Group 1/2, 20/10) and Child-Pugh class A or B (A/B, 17/13). Eleven patients had modified Union for International Cancer Control stage IVA tumors, whereas 19 had stage IVB tumors. All patients had PVTT (Vp3, 6; Vp4, 24). Following sorafenib monotherapy, three patients (10.0%) had a partial response with PVTT revascularization, and nine (30.0%) had stable disease, with a disease control rate of 33.3%. The median overall survival was 3.1 months (95% confidence interval [CI], 2.70 to 3.50), and the median progression-free survival was 2.0 months (95% CI, 1.96 to 2.05). Fatigue and hand-foot skin reactions were the most troublesome side effects.

Conclusions

A limited proportion of patients with advanced HCC and PVTT exhibited a remarkable outcome after sorafenib monotherapy, although the treatment results in this type of patient is extremely poor. Further studies to predict good responders to personalized therapy are warranted.     

Intermediate-advanced hepatocellular carcinoma in Argentina:Treatment and survival analysis

BACKGROUND Hepatocellular carcinoma(HCC) represents the sixteenth most frequent cancer in Argentina. The rise of new therapeutic modalities in intermediate-advanced HCC opens up a new paradigm for the treatment of HCC.AIM To describe real-life treatments performed in patients with intermediateadvanced HCC before the approval of new systemic options.METHODS This longitudinal observational cohort study was conducted between 2009 and2016 in 14 different regional hospitals from Argentina. Included subjects had intermediate-advanced Barcelona Clinic Liver Cancer(BCLC) HCC stages(BCLC B to D). Primary end point analyzed was survival, which was assessed for each BCLC stage from the date of treatment until last patient follow-up or death.Kaplan Meier survival curves and Cox regression analysis were performed, with hazard ratios(HR) calculations and 95% confidence intervals(95%CI).RESULTS From 327 HCC patients, 41% were BCLC stage B, 20% stage C and 39% stage D.Corresponding median survival were 15 mo(IQR 5-26 mo), 5 mo(IQR 2-13 mo)and 3 mo(IQR 1-13 mo)(P 0.0001), respectively. Among BCLC-B patients(n =135), 57% received TACE with a median number of 2 sessions(IQR 1-3 sessions).Survival was significantly better in BCLC-B patients treated with TACE HR =0.29(CI: 0.21-0.40) than those without TACE. After tumor reassessment by RECIST 1.1 criteria following the first TACE, patients with complete response achieved longer survival [HR = 0.15(CI: 0.04-0.56, P = 0.005)]. Eighty-two patients were treated with sorafenib, mostly BCLC-B and C(87.8%). However,12.2% were BCLC-D. Median survival with sorafenib was 4.5 mo(IQR 2.3-11.7 mo); which was lower among BCLC-D patients 3.2 mo(IQR 2.0-14.1 mo). A total of 36 BCLC-B patients presented tumor progression after TACE. In these patients,treatment with sorafenib presented better survival when compared to those patients who received sorafenib without prior TACE [HR = 0.26(CI: 0.09-0.71); P= 0.013].CONCLUSION In this real setting, our results were lower than expected. This highlights unmet needs in Argentina, prior to the introduction of new treatments for HCC.