Multimodality Treatment for Hepatocellular Carcinoma With Portal Vein Tumor Thrombus: A Large-Scale, Multicenter, Propensity Mathching Score Analysis.
ABSTRACT: The optimal treatment for hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) remains controversial. We aimed to investigate the best treatment for patients with HCC with PVTT. From January 2002 to January 2014, the data from all consecutive patients with HCC with PVTT who underwent surgical treatment (ST),TACE,TACE combined with sorafenib (TACE-Sor), or TACE combined with radiotherapy (TACE-RT) in the 4 largest tertiary hospitals in China were analyzed retrospectively. The patients were divided into 3 subtypes according to the extent of PVTT in the portal vein (type I-III). The primary endpoint was overall survival (OS). A total of 1580 patients with HCC with PVTT were included in the study. The median survival times (MST) for ST (n?=?745) for type I, II, and III patients (95% CI) were 15.9 (13.3-18.5), 12.5 (10.7-14.3), and 6.0 (4.3-7.7) months, respectively. The corresponding figures for patients after TACE (n?=?604) were 9.3 (5.6-12.9), 4.9 (4.1-5.7), and 4.0 (3.1-4.9), respectively; for patients after TACE-Sor (n?=?113) 12.0 (6.6-17.4), 8.9 (6.7-11.1), and 7.0 (3.0-10.9), respectively; and for patients after TACE-RT (n?=?118) 12.2 (0-24.7), 10.6 (6.8-14.5), and 8.9 (5.2-12.6), respectively. Comparison among the different treatments for the 3 subtypes of PVTT patients after propensity score (PS) matching showed the effectiveness of ST to be the best for type I and type II PVTT patients, and TACE-RT was most beneficial for type III patients. Treatment was an independent risk factor of OS. ST was the best treatment for type I and II PVTT patients with Child-Pugh A and selected B liver function. TACE-RT should be given to type III PVTT patients.
Project description:A combination of transarterial chemoembolization (TACE) plus sorafenib or radiotherapy (RT) has demonstrated efficacy in patients with advanced hepatocellular carcinoma (HCC). Here, the two combined treatment approaches were compared in patients with HCC and portal vein tumor thrombus (PVTT). Data from 307 patients treated with TACE plus RT (n = 203) or TACE plus sorafenib (n = 104) as first-line treatment for HCC with PVTT were retrospectively evaluated. Using the propensity model to correct selection bias, 87 patients were included from each treatment group. During follow up (median, 12 months) in the entire study population, the median progression-free survival (PFS) and overall survival (OS) were significantly longer in the TACE plus RT group than in the TACE plus sorafenib group (6.5 vs. 4.3 months, respectively; p = 0.017 and 16.4 vs. 12 months, respectively; p = 0.007). Following propensity score matching, the median PFS and OS in the two groups showed no statistically significant difference. Multivariable analysis found no significant association between PFS or OS and the treatment type. In conclusion, this retrospective study of data from patients with advanced HCC with PVTT shows that PFS and OS did not differ significantly in patients treated with TACE plus RT and TACE plus sorafenib.
Project description: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 barcelona clinic 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 meta-analysis 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 resection-based multimodal treatments, transarterial approaches including TACE and TARE, and TACE-based appropriate combination strategies may improve OS of HCC patients accompanying PVTT.
Project description:The aim of the present study was to compare the effectiveness of transarterial chemoembolization (TACE), TACE combined with Jie-du granules (JD), and TACE combined with sorafenib (SOR) for treating patients with unresectable hepatocellular carcinoma (HCC). For this purpose, we conducted a retrospective analysis of data from 266 consecutive patients with unresectable HCC who underwent TACE treatment at the Shanghai Hospital and Eastern Hepatic Surgery Hospital between Jan 2009 and Dec 2010. We prospectively analyzed patient survival and progression times as well as independent predictors, within a follow-up period of 86 months. Patients were divided into TACE-JD (n = 75), TACE-SOR (n = 124) and TACE (n = 67) groups. Median overall survival (OS) times being: TACE-JD, 21.43 months; TACE-SOR, 23.23 months; TACE, 13.97 months (TACE-SOR vs TACE, P < 0.001; TACE-SOR vs TACE-JD, P = 0.852; TACE-JD vs TACE, P < 0.001). The median times to progression (TTP) were as follows: TACE-JD, 8.67 months; TACE-SOR, 5.37 months; TACE, 4.57 months (TACE-SOR vs TACE, P = 0.479; TACE-SOR vs TACE-JD, P < 0.001; TACE-JD vs TACE, P < 0.001). Independent predictors of OS were treatment allocation, Child-Pugh class large tumor, albumin and extrahepatic metastasis. These findings show that patients with unresectable HCC who were administered TACE-JD survived significantly longer compared with those administered TACE or TACE-SOR.
Project description:<h4>Background</h4>Although transarterial chemoembolization (TACE) has been used extensively for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), no consensus has been reached and an evidence base for practice is lacking. This meta-analysis evaluated the efficacy and safety of TACE for treatment of HCC with PVTT.<h4>Methods</h4>Ovid Medline, EMBASE, Web of Knowledge, and Cochrane library databases were searched up to August 2012 for controlled trials assessing TACE in patients with PVTT. Data concerning the study design, characteristics of trials, and outcomes were extracted. Hazard ratio (HR) and 95% confidence interval (CI) were calculated using random effects models.<h4>Results</h4>Eight controlled trials involving 1601 HCC patients were included. TACE significantly improved the 6-month (HR, 0.41; 95% CI: 0.32-0.53; z, 6.28; p = 0.000) and 1-year (HR, 0.44; 95% CI: 0.34-0.57; z, 6.22; p = 0.000) overall survival of patients with PVTT compared with conservative treatment. Subgroup analyses showed that TACE was significantly effective in HCC patients whether with main portal vein (MPV) obstruction or with segmental PVTT. Fatal complications were rare, even in patients with MPV obstruction. Temporary liver decompensation and postembolization syndrome occurred frequently. However, they could be treated successfully with conservative treatment.<h4>Conclusions</h4>TACE, as a safe treatment, has potential for incurring a survival benefit for advanced HCC with PVTT, even with MPV obstruction. Further large randomized controlled trials may be needed to confirm this result.
Project description:<b>Purpose:</b> The study aims to retrospectively investigate the efficacy and safety of sorafenib combined with transarterial chemoembolization (TACE) (TACE+Sor) vs. TACE combined with sorafenib plus immune checkpoint inhibitors (TACE+Sor+ICIs) in treating intermediate and advanced TACE-refractory hepatocellular carcinoma (HCC). <b>Materials and Methods:</b> This study was approved by the ethics committee of Lisui Hospital, Zhejiang University, China. From January 2016 to June 2020, 51 eligible patients with intermediate or advanced TACE-refractory HCC received TACE+Sor (<i>n</i> = 29) or TACE+Sor+ICIs (<i>n</i> = 22). The differences in tumor response, adverse events (AEs), progression-free survival (PFS), and overall survival (OS) were compared between the two groups. Factors affecting PFS and OS were determined by Cox regression. <b>Results:</b> The disease control rate was higher in the TACE+Sor+ICIs group than in the TACE+Sor group (81.82 vs. 55.17%, <i>P</i> = 0.046). Compared with the TACE+Sor group, PFS and OS were prolonged in the TACE+Sor+ICIs group (median PFS: 16.26 vs. 7.30 months, <i>P</i> < 0.001; median OS: 23.3 vs. 13.8 months, <i>P</i> = 0.012). Multivariate analysis showed that BCLC stage, alpha-fetoprotein and treatment were independent factors of PFS; BCLC, Child-Pugh class, ablation after disease progression and treatment were independent predictive factors of OS. Four patients in the TACE+Sor+ICIs group and three patients in the TACE+Sor group suffered from dose reduction or interruption (18.18 vs. 10.34%, <i>P</i> = 0.421). The incidence of ICI-related AEs in the TACE+Sor+ICIs group was well-controlled. <b>Conclusion:</b> The therapeutic schedule of TACE+Sor+ICIs demonstrated efficacy and safety in intermediate and advanced TACE-refractory HCC.
Project description:Background: To explore the effects of postoperative adjuvant transarterial chemoembolization (PA-TACE) on the prognosis of HCC patients with Portal Vein Tumor Thrombus (PVTT) undergoing resection, and to develop a PA-TACE-related nomogram for predicting survival individually. Patients and Methods: Two hundred and ninety-three consecutive HCC patients with PVTT under R0 hepatectomy were recruited. Forty-seven cases had recurrence within one month after surgery. The remaining 246 cases consisted of 90 PA-TACE and 156 non-PA-TACE cases. COX regression analysis was performed for overall survival (OS) or recurrence-free survival (RFS) of these 246 cases, allowing the derivation of independent factors that were integrated into the nomogram. C-index, calibration curves, and risk stratification were performed to evaluate the performance and discriminative power of the nomograms. Results: In 246 patients without recurrence within one month after surgery, the OS and RFS for the PA-TACE group were significantly better than those for the non-PA-TACE group (P<0.0001, P<0.0001, respectively). After Cox regression analysis of OS or RFS, PA-TACE-related nomogram models were constructed. The C-index of the PA-TACE-related nomogram for OS and RFS was 0.72 and 0.73, respectively. Calibration curves revealed a good agreement between predictions and observations for the nomograms. Based on the nomogram-related risk stratification, Kaplan-Meier curves showed powerful discriminative ability. Conclusions: PA-TACE therapy improved the survival of HCC patients with PVTT undergoing hepatectomy. Accurate nomogram models were developed for predicting the individual survival and recurrence of these patients.
Project description:Background:The potential advantages of Jiedu granule (a compound Chinese herbal medicine) combined therapeutic strategies compared with non-Jiedu granule therapeutic strategies for hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) remain unclear. Thus, the purpose of the study was to investigate the safety and efficacy of Jiedu granule for HCC with PVTT. Methods:We retrospectively reviewed the clinical data of 190 patients (94 for non-Jiedu and 96 for Jiedu) with HCC and PVTT from March 2012 to October 2016. Patients were followed up by outpatient examination and telephone till November 2018. Results:It was statistically insignificant between the two groups in baseline characteristics. Procedure-related adverse events (AEs) were observed and compared and most of them were not serious which were easily controlled or subsided naturally. No AE-induced death happened. The median overall survival (OS) rates in the single TACE plus GKR and Jiedu granule combined group were 11.3 months (95% CI: 9.168-13.435) and 15.8 months (95% CI: 13.244-18.339), respectively (p = 0.00047). Conclusions:Jiedu granule combined with TACE plus GKR is safe in HCC patients with PVTT and this Chinese herbal medicine is worthy to be promoted because of better prognosis which needs further research.
Project description:Hepatocellular carcinoma (HCC) has a high predilection with portal vein tumor thrombosis (PVTT). However, part of the PVTT type can be found only under the microscopy, which was namely as type I0. The objective of this study was to establish a simple and inexpensive non-invasive model to predict the presentation of PVTT at HCC patients. A total of 815 HCC patients were retrospectively evaluated and randomly assigned into 2 groups: the training group (n = 408) and validation group (n = 407). A new index model, namely W?AL, was built to predict the presence of PVTT in the training subjects and was further validated in the validation subjects. At the optimal cutoff of 8.90, W?AL identified patients with a hazard ratio (HR) of 7.139 for the presence of PVTT. The area under receiver operating characteristic (AUROC) of W?AL was 0.795 (sensitivity: 71.9%; specificity: 78.6%) for differentiation between PVTT and non-PVTT patients in the training group. The AUROC of W?AL in differentiating patients with PVTT type I0 from non-PVTT patients was 0.748 (sensitivity: 72.1%; specificity: 68.4%) with an HR of 5.355. In addition, W?AL > 8.90 was significantly associated with large tumors, multiple tumor numbers, TNM stage III-IV, metastasis, and overall survival in HCC patients. The novel predictive model represents a simple and inexpensive model that can identify the presence of PVTT in HCC patients with a high degree of accuracy, with important clinical significance in the future therapeutic management of HCC patients.
Project description:To investigate the value of changes in alpha-fetoprotein (AFP) levels for the prediction of radiologic response and survival outcomes in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) who received combined treatment of 3-dimensional conformal radiotherapy (3D-CRT) and transarterial chemoembolization (TACE).A database of 154 HCC patients with PVTT and elevated AFP levels (>20 ng/mL) treated with 3D-CRT and TACE as an initial treatment between August 2002 and August 2008 was retrospectively reviewed. AFP levels were determined 1 month after radiotherapy, and AFP response was defined as an AFP level reduction of >20% from the initial level. Radiologic response, overall survival (OS), and progression-free survival (PFS) rates were compared between AFP responders and non-responders. Propensity-score based matching analysis was performed to minimize the effect of potential confounding bias.The median follow-up period was 11.1 months (range, 3.1-82.7 months). In the propensity-score matching cohort (92 pairs), a best radiologic response of CR or PR occurred in more AFP responders than AFP non-responders (41.3% vs. 10.9%, p < 0.001). OS and PFS were also longer in AFP responders than in non-responders (median OS 13.2 months vs. 5.6 months, p < 0.001; median PFS 8.7 months vs. 3.5 months, p < 0.001).AFP response is a significant predictive factor for radiologic response. Furthermore, AFP response is significant for OS and PFS outcomes. AFP evaluation after combined radiotherapy and TACE appears to be a useful predictor of clinical outcomes in HCC patients with PVTT.
Project description:The prognosis of patients with advanced hepatocellular carcinoma (HCC) is very poor. The outcome of these patients is particularly bleak when the disease is complicated by portal vein tumor thrombosis (PVTT), since the increased portal pressure often causes serious gastrointestinal bleedings. Before the introduction of sorafenib (SOR), a tyrosine kinase inhibitor, no effective treatment was available for patients with advanced disease. SOR is now considered the standard treatment even for patients with tumor thrombosis, although the well-known interference between tyrosine kinase inhibitors and the coagulation pathway calls for caution against their use in this setting. Here, we report the case of a 74-year-old male patient with advanced HCC and PVTT treated with sunitinib (SUN), another multikinase inhibitor. During the third cycle, our patient experienced a life-threatening hematemesis with hemorrhagic shock that required intensive care treatment and SUN discontinuation. However, he completely recovered, and the PET/CT scan performed 1 year after the adverse effect demonstrated no evidence of the tumor together with portal vein recanalization. The short course of SUN causing both tumor response and gastrointestinal bleeding warrants further studies on the effectiveness of SUN in this setting as well as on the duration of treatment with multikinase inhibitors in patients with tumor thrombosis.