Propensity Score Matching Analysis of Changes in Alpha-Fetoprotein Levels after Combined Radiotherapy and Transarterial Chemoembolization for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus.
ABSTRACT: 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:Alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) have been used as diagnostic tools for hepatocellular carcinoma (HCC). However, prediction of outcome using AFP and DCP has not been elucidated. We investigated the clinical role of AFP and DCP as predictors of treatment outcome in patients with HCC undergoing trans-arterial chemoembolization (TACE).Between January 2003 and December 2005, we enrolled 115 treatment-naïve patients who received TACE as an initial treatment modality. An AFP or DCP response was defined as a reduction of more than 50% from the baseline level 1?month after TACE. Patients with AFP?<?20?ng/mL or DCP?<?20 mAU/mL were excluded.The median age was 59?years and the male gender predominated (n?=?81, 70.4%). AFP and DCP response was identified in 91 (79.1%) and 77 (66.9%) patients after TACE. Although progression-free survival (PFS) did not differ according to AFP response (P?=?0.150), AFP responders showed significantly better overall survival (OS) than non-responders (34.9 vs. 13.2?months; P?=?0.002). In contrast, DCP response did not influence either PFS or OS (all P?>?0.05). Multivariate analyses showed that gamma-glutamyltranspeptidase and baseline AFP were predictors of PFS (all P?<?0.05) and that male gender, the presence of liver cirrhosis, baseline DCP, number of measurable tumors and AFP response were independent predictors of OS (all P?<?0.05).AFP response and higher baseline DCP level are significant predictors of OS in treatment-naïve patients with HCC receiving TACE who showed pretreatment elevation of both AFP and DCP.
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:<h4>Background</h4>It is not clear whether tumor marker responses can predict survival during sorafenib treatment in hepatocellular carcinoma (HCC). We investigated whether the ?-fetoprotein (AFP) response is associated with survival in patients with advanced HCC treated with sorafenib.<h4>Methods</h4>We retrospectively reviewed the records of 126 patients with advanced HCC treated with sorafenib between 2007 and 2012. An AFP response was defined as >20% decrease from baseline. At 6-8 weeks after commencing sorafenib, AFP and radiological responses were assessed by modified Response Evaluation Criteria in Solid Tumors.<h4>Results</h4>The median overall survival (OS) and progression-free survival (PFS) were 6.2 and 3.5 months, respectively. Of the study population, a partial response (PR) was identified in 5 patients (4.0%), stable disease (SD) in 65 patients (51.6%), and progressive disease (PD) in 57 patients (44.4%), respectively. AFP non-response was an independent prognostic factor for poor OS (median 10.9 months for AFP response vs 5.2 months for AFP non-response), together with Child-Pugh B, tumor diameter ?10 cm, and portal vein invasion (all P<0.05), and PFS (median 5.3 months for AFP response vs 2.9 months for AFP non-response), together with tumor diameter ?10 cm and portal vein invasion (all P<0.05). SD or PR was more frequently found in AFP responders than in non-responders (72.1% vs 47.0%, respectively; P=0.007). In a sub-group with SD, OS (median 12.7 vs 5.8 months, respectively) and PFS (median 9.1 vs 3.7 months, respectively) were significantly longer in AFP responders than in non-responders (all P<0.05).<h4>Conclusion</h4>Early AFP response may be useful for predicting survival in patients with advanced HCC treated with sorafenib.
Project description:BACKGROUND:Transarterial chemoembolization (TACE), radiofrequency ablation (RFA), and iodine 125 seeds implantation are optional treatments for hepatocellular carcinoma (HCC). The aim of this study is to compare the efficacy of the combined treatment of TACE with iodine 125 seeds implantation (TACE-iodine 125) with TACE with RFA (TACE-RFA) in patients with early- and intermediate-stage HCC. METHODS:The study included 112 patients who were diagnosed with early- and intermediate-stage HCC from January 1, 2014, to May 31, 2018. Among them, 38 patients were treated with TACE-Iodine 125, and 74 with TACE-RFA. The efficacy of the two treatment groups was retrospectively analyzed. To reduced the selective bias, a propensity score matching (PSM) analysis and inverse probability of treatment weighting (IPTW) method were used to compare the outcomes between the two groups. RESULTS:In the absence of PSM and IPTW, the median overall survival (OS) and progression-free survival (PFS) of the TACE-RFA group were slightly longer than those of the TACE-Iodine 125 group (OS: 41?months vs. 36?months; PFS: 18?months vs. 15?months). However, there were no statistically significant differences in the median OS, PFS, and objective response rate (ORR) between the two groups (P?>?0.05). After adjusting the age, gender, Child-Pugh class, Barcelona Clinic Liver Cancer (BCLC) stage, and Alpha-fetoprotein (AFP), TACE-Iodine 125 treatment was not associated with a significant increasing the risks of death (HR: 0.763; 95%CI: 0.403,1.345, P?=?0.320) and recurrence (HR: 1.020; 95%CI: 0.645,1.611, P?=?0.934). After PSM, 35 matched pairs of patients were obtained, and there were no statistically significant differences in the median OS and PFS between the two groups. After IPTW, similar results presented. CONCLUSIONS:The combination of TACE with iodine 125 seeds implantation may represent an effective treatment for patients with early- and intermediate-stage HCC.
Project description: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: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:BACKGROUND:A number of hepatocellular carcinoma (HCC) patients have developed resistance against transcatheter arterial chemoembolization (TACE) treatment. In this study, we aimed to develop a panel of microRNAs (miRs) biomarkers to predict clinical outcomes in HCC patients after TACE treatment. METHODS:The expression level of twenty miRs was evaluated in FFPE tissues collected from 33 HCC patients. We selected four differentially expressed miRs in TACE-responders versus non-responders and re-assessed their expression in 51 serum samples. The expressions of miRs associated with overall survival (OS), progression-free survival (PFS), and treatment outcomes were investigated. The diagnostic accuracy of these miRs in predicting patients' response to TACE was also evaluated. RESULTS:The baseline of miR-106b, miR-107 and miR-133b was significantly elevated (p?<?.001) in sera of TACE-responders while miR-26a was elevated (p?<?.001) in non-responders. miR-26a and miR-133b recorded the highest diagnostic performance as individual classifiers in response to TACE (AUC?=?1.0 and 100% sensitivity and specificity). Intriguingly, miR-133b distinguished complete responders from partial responders and non-responders (AUC???0.90). The PFS was improved (p?<?.05) in the high expression group of miR-31, miR-200b, miR-133b and miR-181a over their low expression group. CONCLUSION:Circulating miR-133b, miR-26a, miR-107 and miR-106 in serum are potential candidates to be utilized as prognostic biomarkers for predication of TACE treatment outcomes in HCC patients.
Project description:Immune checkpoint inhibitors (ICIs) belong to the therapeutic armamentarium in advanced hepatocellular carcinoma (HCC). However, only a minority of patients benefit from immunotherapy. Therefore, we aimed to identify indicators of therapy response. This multicenter analysis included 99 HCC patients. Progression-free (PFS) and overall survival (OS) were studied by Kaplan-Meier analyses for clinical parameters using weighted log-rank testing. Next-generation sequencing (NGS) was performed in a subset of 15 patients. The objective response (OR) rate was 19% median OS (mOS)16.7 months. Forty-one percent reached a PFS > 6 months; these patients had a significantly longer mOS (32.0 vs. 8.5 months). Child-Pugh (CP) A and B patients showed a mOS of 22.1 and 12.1 months, respectively. Ten of thirty CP-B patients reached PFS > 6 months, including 3 patients with an OR. Tumor mutational burden (TMB) could not predict responders. Of note, antibiotic treatment within 30 days around ICI initiation was associated with significantly shorter mOS (8.5 vs. 17.4 months). Taken together, this study shows favorable outcomes for OS with low AFP, OR, and PFS > 6 months. No specific genetic pattern, including TMB, could identify responders. Antibiotics around treatment initiation were associated with worse outcome, suggesting an influence of the host microbiome on therapy success.
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: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.