Role of hepatic resection in patients with intermediate‐stage hepatocellular carcinoma: A multicenter study from Japan

Transarterial chemoembolization (TACE) is recommended for patients with intermediate‐stage (Barcelona Clinic Liver Cancer criteria B [BCLC‐B]) hepatocellular carcinoma (HCC). However, patients with BCLC‐B HCC can differ in background factors related to hepatic function, as well as tumor size and number. In the present study, we clarified the role of hepatic resection in patients with BCLC‐B HCC. A total of 489 BCLC‐B HCC patients with Child–Pugh class A disease initially treated with hepatic resection or TACE were included. After propensity score matching (n = 264), hepatic resection (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.35–0.91) was independently associated with survival in the multivariate analysis. We then divided patients into two groups based on the results of statistical analysis. There were 170 patients treated with resection and 319 with TACE. Child–Pugh score and number of tumors (cut‐off, three tumors) were independently associated with type of HCC treatment in the multivariate analysis. We then divided patients in Group A (Child–Pugh score of 5 and ≤3 tumors; n = 186) and Group B (Child–Pugh score of 6 or ≥4 tumors; n = 303). In Group A, cumulative survival was significantly higher in the hepatic resection group than in the TACE group (P = 0.014). In Cox proportional hazards models, hepatic resection (HR, 0.38; 95% CI, 0.23–0.64) was independently associated with survival in Group A patients. In Group B, treatment status was not associated with overall survival. Hepatic resection should be considered in patients with a Child–Pugh score of 5 and ≤3 tumors, despite having BCLC‐B HCC.     

Investigating Up-to-Seven Criteria and APRI (AST Platelet Ratio) as Prognostic Factors in Intermediate-Stage Hepatocellular Carcinoma Patients Who Received Transarterial Chemoembolization

Background: Transarterial chemoembolization (TACE) is one of the locoregional treatments for intermediate-stage hepatocellular carcinoma (HCC). Multidetector computed tomography (MDCT) is a widely used diagnostic tool for HCC. It can also evaluate tumor size, tumor number, and tumor invasion. This study aimed to determine the median survival time in intermediate-stage HCC patients who underwent TACE and to find out  prognostic factors influencing patients’ survival time after TACE. Methods: A computerized search of medical record database in Maharaj Nakorn ChiangMai Hospital from January 2016 to December 2019 revealed 187 intermediate-stage HCC patients who received TACE as the first-line treatment. Results: The median survival time of patients in this study was 9.9 months (95% CI: 8.3-11.6). The patients with aspartate aminotransferase-to-platelet ratio (APRI) less than 0.5 had a significantly better median survival time as compared with patients with APRI ratio more than 0.5; (13.2 months versus 9.9 months, p-value < 0.05). Univariate and multivariate Cox regression analysis demonstrated that tumor number > 7 and tumor size > 5 centimeters (cm) could be considered as independent parameters predicting poor overall survival time in the sufferers (HR 2.64 95%CI 1.68-4.15 and HR 2.38 95%CI 1.32-4.31, respectively). Conclusion: Based on our findings, patients with intermediate-stage HCC who received TACE had a lower median survival time compared to previous studies. However, we identified APRI less than 0.5, tumor size less than 5 cm, and tumor number less than 7 as prognostic factors improving survival time in intermediate-stage HCC patients.     

Second-line treatment with nivolumab,cabozantinib, regorafenib,or best supportive care in patients with advanced hepatocellular carcinoma: analysis at a Hispanic-majority NCI-designated cancer center

BackgroundIn the last four years, six regimens were approved by the Food and Drug Association as second-line therapies for advanced hepatocellular carcinoma (HCC). However, there are significant differences between real-world and clinical trial populations. We analyzed survival and toxicities among second-line therapies for HCC in our population.MethodsWe performed a retrospective cohort study of patients with advanced HCC who received second-line therapies (tyrosine kinase inhibitor or TKI; immunotherapy or IO) or best supportive care (BSC) at a tertiary-referral cancer center serving the South Texas region. Progression-free survival (PFS) was determined, and adverse events were compared between therapies.ResultsIn our cohort, median age was 60 years (n=65), and 49 (75%) were Hispanic. 58 (89%) patients received second-line therapy. Child-Pugh (CP) score of cohort: A, 18%; B, 55%; C, 26%. Median PFS (mPFS) was 3.1 months with TKI (n=6), 3.3 months with IO (n=27), and 1.3 months with BSC (n=25). There was improved survival with IO compared to BSC [hazards ratio (HR) =0.31; 95% confidence interval (CI): 0.15–0.63; P=0.0014]. There was no significant difference comparing IO to TKI (HR =0.94; 95% CI: 0.31–2.86; P=0.92), but a trend to improved PFS with TKI when compared to BSC (HR =0.33; 95% CI: 0.10–1.04; P=0.058). TKI group had significantly more rash (P=0.01) and hand-foot syndrome (P<0.001) compared to IO and BSC.ConclusionsOur Hispanic-majority cohort with varying liver dysfunction, including CP-B & C cirrhosis, were more likely to receive IO or BSC. Both second-line treatment groups, IO or TKI, demonstrated increased mPFS compared to BSC and were tolerable compared to BSC, with expected toxicity per class of drug.     

The Impact of Sorafenib in Combination with Transarterial Chemoembolization on the Outcomes of Intermediate-Stage Hepatocellular Carcinoma

Background: We investigated the treatment outcomes and hepatic reserve of transarterial chemoembolization (TACE)-refractory patients with recurrent advanced hepatocellular carcinoma (HCC) treated with TACE plus sorafenib. Methods: Forty-one patients with intermediate-stage HCC defined as being TACE refractory on imaging were treated with sorafenib and TACE between 2009 and 2012 and comprised the combination treatment group. Twenty-nine patients who received repeated TACE after becoming refractory to TACE between 2005 and 2008 comprised the TACE continuation group. Results: Although the interval between successive rounds of TACE was significantly shorter before the patients developed TACE refractoriness, it was significantly longer after the development of TACE refractoriness, in the combination treatment group compared with the TACE continuation group. The appearance of extrahepatic spread and/or vascular invasion differed significantly between the two groups. The median overall survival was significantly longer in the combination treatment group than in the TACE continuation group (20.5 vs. 15.4 months, respectively; hazard ratio = 2.04; 95% confidence interval = 1.20–3.48). The 3-year overall survival rate was 33.4% in the combination treatment group and 3.5% in the TACE continuation group. Downstaging of the Child–Pugh class was significantly less frequent in the combination treatment group than in the TACE continuation group. In COX proportional hazards analyses, sorafenib plus TACE resulted in a better prognosis compared with repeated TACE. Conclusions: Treatment with sorafenib plus TACE in TACE-refractory patients with intermediate-stage HCC resulted in longer intervals between TACE rounds, better maintenance of hepatic reserve, and significantly longer OS compared with repeated TACE.     

Adjuvant transarterial chemoembolization improves survival outcomes in hepatocellular carcinoma with microvascular invasion: A systematic review and meta-analysis

BackgroundThe benefits of adjuvant transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI) remain controversial. We compared the efficacy and safety of adjuvant TACE and hepatic resection (HR) alone for HCC patients with MVI.MethodsThe PubMed, EMBASE, Cochrane Library, VIP, Wan Fang, and Sino Med databases were systematically searched to compare adjuvant TACE and HR alone for the treatment of HCC with MVI from inception to January 1, 2019. The study outcomes, including overall survival (OS) and disease-free survival (DFS), were extracted independently by two authors.Results12 trials involving 2190 patients were evaluated. A meta-analysis of 11 studies suggested that the 1-, 3-, and 5-year overall survival (OS) rates (OR = 0.33, P < 0.001; OR = 0.49, P < 0.001; and OR = 0.59, P < 0.01; respectively), favored adjuvant TACE over HR alone. 11 studies were included in the meta-analysis of DFS, and adjuvant TACE showed better 1-, 3-, and 5-DFS (OR = 0.45, P < 0.001; OR = 0.50, P < 0.001; and OR = 0.58, P < 0.001; respectively) compared to HR alone. Subgroup analysis demonstrated that adjuvant TACE could benefit HCC patients with MVI with tumor diameter >5 cm or multinodular tumors.ConclusionAdjuvant TACE may improve OS and DFS for HCC patients with MVI compared to HR alone and should be recommended for selected HCC patients with MVI. However, these results need to be validated through further high-quality clinical studies.Lay summaryThe benefits of adjuvant TACE in HCC patients with microvascular invasion remain controversial. Twelve studies involving 2190 patients were include in our meta-analysis. Adjuvant TACE may improve OS and DFS for HCC patients with MVI compared to HR alone and should be recommended for selected HCC patients with MVI.     

Transarterial chemoembolization versus best supportive care for patients with hepatocellular carcinoma with portal vein tumor thrombus：a multicenter study

BackgroundThis study aims to compare the efficacy and safety of treatment after transarterial chemoembolization(TACE) with best supportive care (BSC) in patients with hepatocellular carcinoma (HCC) with PVTT.MethodsThis retrospective study was conducted on 1,040 patients with HCC with PVTT who were treated either with TACE (n = 675) or BSC (n = 365). BSC did not include sorafenib. The two groups of patients were compared with or without propensity score matching. A subgroup analysis was subsequently performed by stratifying patients according to the stages of PVTT in the Cheng's PVTT classification.ResultsIn PVTTtypes I-III, TACE was associated with significantly better overall survival (OS) thanBSC (P < 0.05). Within each type of PVTT for patients who received TACE or BSC, OS was significantly worse in patients with type IVPVTT than in any of the other three types of PVTT (all P < 0.05). TACE was associated with better long-termOS than BSC after propensity score matching or on stratification by the PVTT types.ConclusionTACE was associated with better OS than BSC in HCC patients with PVTT types I-III but not type IV. Patients with type IV PVTT showed the worst prognosis, regardless of whether TACE or BSC was used.     

Population-based matching comparison between radiofrequency ablation and percutaneous ethanol or acetic acid injection for hepatocellular carcinoma

BackgroundLoco-regional therapies are evolving for hepatocellular carcinoma (HCC) treatment. Radiofrequency ablation (RFA) has changed the landscape in treating HCC; however, percutaneous ethanol or acetic acid injection (PEI/PAI) remains a widely used and easily performed technique by experienced clinicians. Nevertheless, the effectiveness of RFA compared to that of PEI/PAI remains unclear.MethodsRecords of 73,136 patients with newly diagnosed HCC between 2007 and 2013 were drawn from the Taiwan Cancer Registry. The primary outcome measures were the overall survival and local recurrence-free survival. Propensity score matching (PSM) was performed to compare the effectiveness of RFA and PEI. Median follow-up time was 61.6 months (36–120 months).ResultsAfter PSM, 4496 patients diagnosed with stage I-III HCC, who were initially treated with RFA (3372 patients) or PEI/PAI (1124 patients), were assessed. Compared to PEI/PAI, patients treated with RFA had better 5- and 9-year overall survival, cancer-specific survival, disease-free survival, and local recurrence-free survival. Median overall survival and recurrence-free survival of patients treated with RFA vs PEI/PAI were 61.5 vs 41.9 months and 72.1 vs 45.2 months, respectively. Multivariate Cox model analysis revealed that, except for patients with high cell grade or advanced stage, RFA resulted in better overall survival (HR: 0.74, 95% CI 0.68–0.81, P < 0.001) and local recurrence-free survival (HR: 0.69, 95% CI 0.63–0.75, P < 0.001) than PEI/PAI.ConclusionsRFA provides advantages over conventional PEI/PAI for HCC. Considering technological advances in instruments, loco-regional therapies for HCC can be employed in carefully selected patients.     

Survival benefit of patients with inoperable hepatocellular carcinoma treated by a combination of transarterial chemoembolization and percutaneous ethanol injection—a single-center analysis including 132 patients

Hepatocellular carcinoma (HCC) is one of the most severe sequelae of chronic liver disease. The only potentially curative therapeutic options are surgical resection and orthotopic liver transplantation. In most HCC patients, however, at clinical presentation the tumors are unresectable because of multicentricity or poor hepatic functional reserve due to pre-existing cirrhosis or not transplantable because of too advanced tumor stage or severe co-morbidity. In clinical practice, therefore, percutaneous ethanol injection (PEI) and transarterial chemoembolization (TACE) are widely used non-surgical therapeutic strategies. We prospectively analyzed the clinical factors determining the prognosis of 132 inoperable HCC patients and assessed the feasibility, therapeutic efficacy and safety of PEI, TACE and a combination thereof. Mean age of patients was 64 years; 95% of patients had liver cirrhosis and 39% were Okuda stage I, 48% stage II and 13% stage III. Fifteen patients were treated by PEI (group 1), 33 by TACE (group 2), 39 by TACE and PEI (group 3) and 45 received best supportive care (group 4). Survival correlated with the Child-Pugh class of liver cirrhosis and the Okuda stage of HCC. Favorable prognostic parameters were alpha-fetoprotein (AFP) levels <100 ng/ml and absence of portal vein thrombosis. Median survival time was 18 months in group 1 [interquartile range (IQR) 10–19], 8 months in group 2 (IQR 5–15), 25 months in group 3 (IQR 13–36) and 2 months in group 4 (IQR 1–9). Multivariate analysis revealed that patients treated with a combination of TACE and PEI have a significantly better survival than patients receiving either PEI or TACE only (p = 0.001). Patients with inoperable HCCs treated by the combination of TACE and PEI have a clear survival benefit. A favorable outcome can be expected in patients with compensated cirrhosis, a low Okuda stage, a baseline AFP level <100 ng/ml and absence of portal vein thrombosis. Int. J. Cancer (Pred. Oncol.) 79:601–605, 1998. © 1998 Wiley-Liss, Inc.     

Minimally invasive surgery versus percutaneous radiofrequency ablation for early-stage hepatocellular carcinoma: Results from a high-volume liver surgery center in East Asia

Background & aimsThe outcomes of minimally invasive surgery (MIS) vs. percutaneous radiofrequency ablation (RFA) in treating early-stage hepatocellular carcinoma (HCC) remain inconclusive. This study thus aimed to compare the outcomes of both treatments for early-stage HCCs.MethodsThis retrospective study consecutively enrolled patients with newly diagnosed early-stage HCCs treated with MIS or percutaneous RFA between 2011 and 2018. Outcomes were compared between the MIS and RFA groups both before and after 1:1 propensity score matching (PSM).ResultsA total of 119 and 481 patients underwent MIS and percutaneous RFA, respectively. Patients undergoing percutaneous RFA exhibited older age (p = 0.007) and higher rates of Child–Pugh class B (p < 0.001) and multifocal disease (p < 0.001). The median overall survival (OS) was 73.7 months in the MIS group, which was significantly higher than that for the RFA group of 65.1 months (p = 0.003). 50% HCC recurrence after MIS was not reached. The mean recurrence-free survival (RFS) was 49.6 months for the MIS group, which was significantly higher than the RFA group of 41.3 months (p < 0.001). On multivariate analysis, age ≥65 (HR: 1.61; 95% CI: 1.13–2.31, p = 0.009), RFA (HR: 2.21; 95% CI: 1.14–4.29, p = 0.019), and Child–Pugh class B (HR: 2.03; 95% CI: 1.29–3.21, p = 0.002) remained risk factors for OS, and RFA (HR: 2.18; 95% CI: 1.42–3.35; p < 0.001) remained a risk factor for RFS. After PSM, 103 patients were included in each group. No significant difference in OS was identified (p = 0.198), but RFS was higher in the MIS group than the RFA group (p = 0.003). Severe postoperative complications occurred at the same rate (1%) in both groups (p > 0.99).ConclusionAfter PSM, severe postoperative complication and OS rates were found to be comparable between the MIS and RFA groups, but RFS was higher in the MIS group than the RFA group, suggesting that MIS may have better outcomes for patients with early-stage HCC.     

Long-term oncologic results of anatomic vs. parenchyma-sparing resection for hepatocellular carcinoma. A propensity score-matching analysis

Purpose

The extent of liver resection for the optimal treatment of hepatocellular carcinoma (HCC) is debated. The purpose of this study was to compare the impact of anatomic resection (AR) vs. parenchyma-sparing resection (PSR) on disease recurrence and patient survival.

巴塞罗那肝癌临床分期B期肝细胞性肝癌手术与TACE疗效比较

  目的  比较肝细胞性肝癌(HCC)巴塞罗那肝癌临床(BCLC)分期B期患者行肝切除术及经肝动脉化疗栓塞(TACE)治疗的疗效。  方法  回顾性分析2003年1月至2006年8月共222例BCLC B期、Child-PughA级HCC患者的生存资料, 采用t检验及秩和检验进行组间比较, 采用Cox模型分析危险因素, Kaplan-Meier曲线法分析总生存率。  结果  222例患者中, 肝切除术治疗118例, TACE治疗104例。肝切除术组患者的1、3、5年总生存率分别为76%、46%、37%, 中位生存期为29个月; TACE组患者的总生存率分别为53%、19%、7%, 中位生存期为11个月(P < 0.05)。Cox回归模型提示治疗方式TACE是影响预后的危险因素。  结论  肝切除术较TACE治疗可能更能提高BCLC B期、Child-Pugh A级HCC患者的总生存率。BCLC B期HCC的治疗方式应该按不同的亚组行更为细致的划分。      

Sorafenib for non-selected patient population with advanced hepatocellular carcinoma: efficacy and safety data according to liver function

Objective

Sorafenib is the standard treatment of patients with advanced hepatocellular carcinoma, regardless of the liver functional reserve. We present a single institutional series of Child–Pugh A and Child–Pugh B patients treated with sorafenib with the aim to establish the efficacy and safety of sorafenib in patients of daily clinical conditions and to compare these results between Child–Pugh A and Child–Pugh B patients.

Materials and methods

A total of 51 patients were treated with sorafenib 400 mg/12 h until disease progression or unacceptable toxicity.

Results

The median progression-free survival and overall survival for the overall population were 3.5 and 8.2 months, respectively, with a 1-year survival rate of 27 %. Overall survival was significantly longer for patients Child–Pugh A compared with those with Child–Pugh B liver function (8.7 vs. 4.7 months, respectively). The most common adverse events were fatigue (62.7 %), diarrhea (58 %), hypertension (31.3 %), and hand–foot syndrome (31.3 %), and in most cases grade 1 or 2 according to the NCI-CTC 3.0. Grade 4 liver-related events occurred mainly in Child–Pugh B patients with decompensated cirrhosis at the time of sorafenib initiation (54.5 % of that group).

Discussion

The benefit of sorafenib in Child–Pugh B patients, if exist, may be limited by frequent liver-related events, especially in decompensated patients, and then, toxicity and impact in quality of life should be carefully monitored.     

Efficacy and Toxicity of Stereotactic Body Radiotherapy for Early to Advanced Stage Hepatocellular Carcinoma – Initial Experience From an Australian Liver Cancer Service

AimsIntrahepatic progression remains the predominant mode of cancer-related death in hepatocellular carcinoma (HCC) underscoring the need for effective local therapies. We report our initial experience with liver stereotactic body radiotherapy (SBRT) in the management of early to advanced stage HCC at an Australian tertiary liver cancer service.Materials and methodsPatients with liver-confined HCC unsuitable for surgical resection or thermal ablation treated with SBRT between October 2013 and December 2018 were retrospectively evaluated. The primary end point was freedom from local progression. Secondary end points were progression-free survival, disease-specific survival, overall survival and toxicity.ResultsNinety-six patients were treated for 112 lesions (median size 3.8 cm, range 1.5–17 cm). The median follow-up was 13 months (range 3–65). Forty-six patients had received prior local therapies (median 1, range 1–5), 83 (86%) patients had cirrhosis with baseline Child–Pugh scores of A (88%) and B7–8 (12%). Fifty-nine (61%) patients had Barcelona Clinic Liver Cancer (BCLC) stage 0/A disease and 37 (39%) had stage B/C. Macrovascular invasion was present in 20 (21%). The median biologically effective dose (BED₁₀) was 86 and 60 Gy for the BCLC 0/A and B/C cohorts, respectively. Freedom from local progression at 18 months was 94% for BCLC 0/A and 74% for BCLC B/C. Progression-free survival and overall survival at 12 months were 80 and 95% for BCLC 0/A and 40 and 71% for BCLC B/C, respectively. Five patients (7%) with cirrhosis and without disease progression had an increase in Child–Pugh score >1 within 3 months of SBRT, four of whom had intercurrent infections. Clinical toxicities grade ≥2 were reported in 20% of patients.ConclusionSBRT is an effective ablative modality for early stage HCC with low rates of significant toxicity. Lower dose SBRT can provide durable local control for advanced stage HCC. However, out-of-field relapse remains common, providing a rationale to investigate SBRT in combination with other therapies.     

Functional polymorphisms in the NPAS2 gene are associated with overall survival in transcatheter arterial chemoembolization‐treated hepatocellular carcinoma patients

The functional abnormality of circadian regulation genes is involved in the development and progression of hepatocellular carcinoma (HCC). However, the association between functional single nucleotide polymorphisms (SNPs) in circadian gene NPAS2 and the overall survival of HCC patients treated with transcatheter arterial chemoembolization (TACE) has never been investigated. Six functional SNPs in the NPAS2 gene were genotyped using the Sequenom iPLEX genotyping system in a cohort of 448 unresectable Chinese patients with HCC treated with TACE. Multivariate Cox proportional hazards model and Kaplan–Meier curves were used for the prognosis analysis. We found that two SNPs, rs1053096 and rs2305160, in the NPAS2 gene showed significant associations with overall death risk in HCC patients in the recessive model (hazard ratio [HR] = 1.48; 95% confidence interval [CI], 1.13–1.94; P = 0.004) and in the dominant model (HR = 1.63; 95% CI, 1.29–2.07; P < 0.001), respectively. Moreover, we observed a cumulative effect of these two SNPs on HCC overall survival, indicating a significant trend of increasing death risk with increasing number of unfavorable genotypes (P for trend < 0.001). Compared with the patients without any unfavorable genotypes, the HRs for patients with one and two unfavorable genotypes were 1.41 (95% CI, 1.10–1.82; P = 0.007) and 2.09 (95% CI, 1.46–2.97, P < 0.001), respectively. The haplotype and diplotype analyses further characterized the association between NPAS2 genotype and survival of HCC patients. Our results for the first time suggest that NPAS2 gene polymorphisms may serve as an independent prognostic marker for HCC patients treated with TACE.     

Randomized phase II study of axitinib versus placebo plus best supportive care in second-line treatment of advanced hepatocellular carcinoma

BackgroundThe efficacy and safety of axitinib, a potent and selective vascular endothelial growth factor receptors 1–3 inhibitor, combined with best supportive care (BSC) was evaluated in a global, randomized, placebo-controlled phase II trial in patients with locally advanced or metastatic hepatocellular carcinoma (HCC).Patients and methodsPatients with HCC and Child–Pugh Class A who progressed on or were intolerant to one prior antiangiogenic therapy were stratified by tumour invasion (presence/absence of extrahepatic spread and/or vascular invasion) and region (Asian/non-Asian) and randomized (2:1) to axitinib/BSC (starting dose 5 mg twice-daily) or placebo/BSC. The primary end point was overall survival (OS).ResultsThe estimated hazard ratio for OS was 0.907 [95% confidence interval (CI) 0.646–1.274; one-sided stratified P = 0.287] for axitinib/BSC (n = 134) versus placebo/BSC (n = 68), with the median (95% CI) of 12.7 (10.2–14.9) versus 9.7 (5.9–11.8) months, respectively. Results of prespecified subgroup analyses in Asian versus non-Asian patients or presence versus absence of tumour invasion were consistent with the overall population. Improvements favouring axitinib/BSC (P < 0.01) were observed in secondary efficacy end point analyses [progression-free survival (PFS), time to tumour progression (TTP), and clinical benefit rate (CBR)], and were retained among Asian patients in the prespecified subgroup analyses. Overall response rate did not differ significantly between treatments and patient-reported outcomes favoured placebo/BSC. Most common all-causality adverse events with axitinib/BSC were diarrhoea (54%), hypertension (54%), and decreased appetite (47%). Baseline serum analyses identified potential new prognostic (interleukin-6, E-selectin, interleukin-8, angiopoietin-2, migration inhibitory factor, and c-MET) or predictive (E-selectin and stromal-derived factor-1) factors for survival.ConclusionsAxitinib/BSC did not improve OS over placebo/BSC in the overall population or in stratification subgroups. However, axitinib/BSC resulted in significantly longer PFS and TTP and higher CBR, with acceptable toxicity in patients with advanced HCC.Trial RegistrationClinicalTrials.gov, NCT01210495.     

Early sorafenib‐related adverse events predict therapy response of TACE plus sorafenib: A multicenter clinical study of 606 HCC patients

The purpose of our study was to test the hypothesis that sorafenib‐related dermatologic adverse events (AEs) as an early biomarker can predict the long‐term outcomes following the combination therapy of transarterial chemoembolization (TACE) plus sorafenib (TACE‐S). The intermediate‐stage hepatocellular carcinoma patients who received either TACE‐S or TACE‐alone treatment were consecutively included into analysis. In the TACE‐S group, patients with ≥ grade 2 dermatologic AEs within the first month of sorafenib initiation were defined as responders; whereas those with < grade 2 were defined as nonresponders. In the TACE‐S group, the median overall survival (OS) of the responders was significantly longer than that of nonresponders (28.9 months vs. 16.8 months, respectively; p = 0.004). Multivariate analysis demonstrated that nonresponders were significantly associated with an increased risk of death compared with responders (HR = 1.9; 95% confidence Interval‐CI: 1.3–2.7; p = 0.001). The survival analysis showed that the median OS was 27.9 months (95% CI: 25.0–30.8) among responders treated with TACE‐S vs.18.3 months (95% CI: 14.5–22.1) among those who received TACE‐alone (p = 0.046). The median time to progression was 13.1 months (95% CI: 4.4–21.8) in the TACE‐S group, a duration that was significantly longer than that in the TACE‐alone group [5 months (95% CI: 6.4–13.3), p = 0.014]. This study demonstrated that sorafenib‐related dermatologic AEs are clinical biomarkers to identify responders from all of the patients for TACE‐S therapy. Sorafenib‐related dermatologic AEs, clinical biomarkers, can predict the efficacy of TACE‐S in future randomized controlled trials.     

Comparable benefits of HCV eradication by direct acting antivirals and interferon-based therapy in patients with hepatocellular carcinoma undergoing surgical resection

Whether direct-acting antivirals (DAA) provide comparable survival benefit with interferon (IFN)-based therapy remains unclear. The aim of this study was to compare the outcomes after achieving SVR by IFN-based and DAA therapy after resection of HCV-related hepatocellular carcinoma (HCC). Consecutive 285 patients receiving curative resection for HCV-related HCC were retrospectively enrolled, including 103 (36.1%) and 69 (24.2%) patients with IFN-based and DAA therapy, respectively. Factors associated with recurrence, overall survival (OS) and hepatic decompensation-free survival were evaluated. The SVR rate of DAA was 95.7% in HCC patients. During a median follow-up period of 49.6 months, 102 (35.8%) patients died and 63 (24%) developed hepatic decompensation. By multivariate analysis, SVR by DAA or IFN-based therapy was not associated with early or late HCC recurrence. Achieving SVR (by IFN-based therapy: HR=0.321, P<0.001; by DAA: HR=0.396, P=0.011), BCLC stage B-C (HR=1.914, P=0.024), FIB-4 score >3.25 (HR=1.664, P=0.016) and microvascular invasion (HR=1.603, P=0.048) were independent predictors of OS. Achieving SVR (by IFN-based therapy: HR=0.295, P<0.001; by DAA: HR=0.193, P=0.002), BCLC stage B-C (HR=2.975, P=0.001), GGT >70 U/L (HR=1.931, P=0.015) and cirrhosis (HR=2.035, P=0.007) were independent predictors of decompensation-free survival. The benefit of achieving SVR was consistently observed in cirrhotic and non-cirrhotic patients, and in patients with and without HCC recurrence. In conclusion, achieving SVR by either DAA or IFN-based therapy provide comparable and significant reduction of mortality and hepatic decompensation after surgical resection of HCV-related HCC. DAA therapy should be prescribed for all HCC patients after curative surgical resection.     

Health-Related Quality of Life of Patients with Intermediate Hepatocellular Carcinoma after Liver Resection or Transcatheter Arterial Chemoembolization

Background: The aim of our present study was to compare quality of life (QoL) between intermediate-stage(BCLC-B) HCC patients who had undergone either liver resection or transcatheter arterial chemoembolization(TACE). Materials and Methods: A total of 102 intermediate-stage HCC patients participated in our study,including 58 who had undergone liver resection and 44 who had undergone TACE. Baseline demographiccharacteristics, tumor characteristics, and long-term outcomes, such as tumor recurrence, were compared andanalyzed. QoL was assessed using the Short Form (SF)-36 health survey questionnaire with the mental andphysical component scales (SF-36 MCS and PCS). This questionnaire was filled out at HCC diagnosis and 1,3, 6, 12, 24 months after surgery. Results: For the preoperative QoL evaluation, the 8 domains related to QoLwere comparable between the two groups. The PCS and MCS scores were significantly decreased in both theTACE and resection groups at1 month after surgery, and this decrease was greater in the resection group.These scores were significantly lower in the resection group compared with the TACE group (P<0.05). However,these differences disappeared at 3 and 6 months following surgery. One year after surgery, the resection groupshowed much higher PCS scores than the TACE patients (P=0.018), and at 2 years after surgery, the PCS andMCS scores for the resection group were significantly higher than those for the TACE group (P<0.05). Elevenpatients (19.0%) in the resection group and 17 (38.6%) in the TACE group suffered HCC recurrence (P<0.05).Univariate and multivariate analyses indicated that tumor recurrence (HR=1.211, 95%CI: 1.086-1.415, P=0.012)was a significant risk factor for poorpostoperative QoL in the HCC patients.Conclusions: Due to its effectson reducing HCC recurrence and improving long-term QoL, liver resection should be the first choice for thetreatment of patients with intermediate-stage HCC.     

Transarterial chemoembolisation for advanced hepatocellular carcinoma: results from a North American cancer centre

AimsIn Asian countries, transarterial chemoembolisation (TACE) has long been used for palliation of unresectable hepatocellular carcinoma (HCC) without strong evidence of improved survival or quality of life. In 2002, a survival benefit of TACE was shown in two randomised controlled trials in Europe and Hong Kong. The effectiveness of interventions for HCC is influenced by geographical factors related to diverse patient characteristics and protocols. Therefore, the validation of TACE as palliative modality for unresectable HCC requires confirmation in diverse patient populations. The aim of the present study was to assess the effectiveness of TACE for HCC in a North American population.Materials and methodsThis was a single centre prospective cohort study. Child–Pugh A cirrhosis or better patients with unresectable HCC and without radiological evidence of metastatic disease or segmental portal vein thrombosis were assessed between November 2001 and May 2004. Of 54 patients who satisfied the inclusion criteria, 47 underwent 80 TACE sessions. Chemoembolisation was carried out using selective hepatic artery injection of 75 mg/m² doxorubicin and lipiodol followed by an injection of embolic particles when necessary. Repeat treatments were carried out at 2–3 month intervals for recurrent disease. The primary outcome was overall survival; secondary outcomes were morbidity and tumour response.ResultsThe survival probabilities at 1, 2 and 3 years were 76.6, 55.5 and 50%, respectively. At 6 months after the first intervention, 31% of patients had a partial response and 60% had stable disease by RECIST criteria. Minor adverse events occurred after 39% of TACEs and major adverse events after 20% of sessions, including two treatment-related deaths (4% of patients). One patient had complete cancer remission after undergoing three TACE treatments. Further progression of tumour growth was prevented in 91% of tumours at the 6 month point after the first TACE. At 3 months, serum levels of the tumour marker alpha-feto protein were significantly reduced in patients with elevated levels before TACE.ConclusionsThe survival probabilities at 1 and 2 years after TACE were comparable with results in randomised studies from Europe and Asia. Most patients tolerated TACE well, but clinicians need to be aware that moderately severe side-effects require close monitoring and prompt intervention.     

Comparative dosing and efficacy of sorafenib in hepatocellular cancer patients with varying liver dysfunction

Background

Sorafenib is the only FDA-approved systemic therapy for advanced hepatocellular carcinoma (HCC). In clinical practice, dose reductions are often required, although there are limited efficacy data related to dose modifications. Given the prevalence of HCC in South Texas, we assessed the efficacy and safety of sorafenib therapy in relation to dose and Child Pugh (CP) score.

Methods

A retrospective analysis was done of advanced HCC patients, starting sorafenib at 400 mg twice daily, or at physician discretion at 400 mg daily, with the goal of titrating to twice daily. Overall survival (OS) and progression-free survival (PFS) were assessed.

Results

Among 107 patients, median OS (mOS) was 10.2 months; median PFS (mPFS) was 5.2 months. mOS for sorafenib 400 mg/day was 6.6 vs. 800 mg/day was 12.8 months [hazard ratio (HR), 0.59; P=0.04]; mPFS was 3.5 vs. 5.9 months, respectively (HR, 0.66; P=0.07). For Child Pugh A class (CP-A) patients, mOS was 15.8 months for 400 mg/day vs. 12.8 months for 800 mg/day (HR, 1.48; P=0.35); mPFS was 9.0 vs. 5.9 months, respectively (HR, 1.23; P=0.56). For Child Pugh B class (CP-B) patients, mOS was 5.0 months for 400 mg/day vs. 11.2 months for 800 mg/day (HR, 0.33; P=0.002); mPFS was 2.1 vs. 5.6 months, respectively (HR, 0.41; P=0.006). No differences in adverse events (AEs) were observed in CP-A vs. CP-B.

Conclusions

Patients with CP-A or CP-B advanced HCC should be offered sorafenib at 400 mg twice daily with optimal management of AEs in order to improve survival.