Combined transarterial chemoembolization and tislelizumab for patients with unresectable hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)often presents as unresectable,necessitating effective treatment modalities.Combining transarterial chemoembolization(TACE)with immunotherapy and targeted therapy has shown promise,yet real-world evidence is needed.AIM To investigate effectiveness and safety of TACE with tislelizumab±targeted therapy for unresectable HCC in real-world setting.METHODS This retrospective study included patients with unresectable HCC receiving combined treatment of TACE and tislelizumab.The clinical outcomes included progression-free survival(PFS),overall survival(OS),objective response rate(ORR),and disease control rate(DCR).All patients were evaluated according to the mRECIST criteria.The adverse event(AE)was also assessed.RESULTS In this study of 56 patients with median follow-up of 10.9 months,7 had previous immunotherapy.Tislelizumab was administered before TACE in 21(37.50%)and after in 35(62.50%)patients,with 91.07%receiving concurrent targeted therapy.Median PFS was 14.0(95%CI:7.0-18.00)months,and OS was 28(95%CI:2.94-53.05)months.Patients with prior immunotherapy had shorter PFS(6 vs.18 months,P=0.006).Overall ORR and DCR were 82.14%and 87.50%.Grade≥3 treatment-related AEs included increased alanine aminotransferase(8.93%),aspartate aminotransferase(10.71%),and total bilirubin(3.57%).CONCLUSION The combination of TACE and tislelizumab,with or without targeted therapy,demonstrated promising efficacy and safety in unresectable HCC,especially in immunotherapy-naive patients,warranting further prospective validation studies.

Transarterial chemoembolization as initial treatment for unresectable hepatocellular carcinoma in southern China

AIM:To identify prognostic factors from pretreatment variables of the initial transarterial chemoembolization(TACE)procedure in unresectable hepatocellular carcinoma(HCC). METHODS:One thousand and five hundred and sixtynine patients with unresectable HCC underwent TACE as initial treatment were retrospectively studied.Pretreatment variables of the initial TACE procedure with a P value less than 0.05 by univariate analysis were subjected to Cox proportional hazards model. RESULTS:The median overall survival time and 1-, 5-,10-year survival rates were 10.37 mo,47%,10%, and 7%,respectively.A Cox proportional hazard model showed that 8 pretreatment factors of regional lymphnodes metastasis,Child-Pugh class,macrovascular invasion,greatest dimension,α-fetoprotein(AFP), Hepatitis virus B,tumor capsule,and nodules were independent prognostic factors.Patients with multimodality therapy have better survival than those with TACE treatment only. CONCLUSION:Tumor status,hepatic function reserve,AFP,and hepatitis virus B status were independent prognostic factors for unresectable HCC.Distant metastasis might not be a contraindication to TACE. Multimodality therapy might improve survival.

Transarterial chemoembolization and bland embolization for hepatocellular carcinoma

Transarterial chemoembolization(TACE)is the first line treatment for patients with intermediate stage hepatocellular carcinoma but is also increasingly being used for patients on the transplant waiting list to prevent further tumor growth.Despite its widespread use,TACE remains an unstandardized procedure,with variation in type and size of embolizing particles,type and dose of chemotherapy and interval between therapies.Existing evidence from randomized controlled trials suggest that bland transarterial embolization(TAE)has the same efficacy with TACE.In the current article,we review the use of TACE and TAE for hepatocellular carcinoma and we focus on the evidence for their use.

Transarterial chemoembolization combined with recombinant human adenovirus type 5 H101 prolongs overall survival of patients with intermediate to advanced hepatocellular carcinoma: a prognostic nomogram study

Background: Patients with intermediate to advanced hepatocellular carcinoma(HCC) are most commonly treated with transarterial chemoembolization(TACE). Previous studies showed that TACE combined with recombinant human adenovirus type 5(H101) may provide a clinical survival benefit. In the present study, we aimed to determine the survival benefit of TACE with or without H101 for patients with intermediate to advanced HCC and to develop an e ective nomogram for predicting individual survival outcomes of these patients.Methods: We retrospectively collected data from 590 patients with intermediate to advanced HCC who were treated at Sun Yat?sen University Cancer Center between January 2007 and July 2015. After propensity score matching, 238 patients who received TACE with H101(TACE with H101 group) and 238 patients who received TACE without H101(TACE group) were analyzed. Overall survival(OS) was evaluated using the Kaplan–Meier method; the nomogram was developed based on Cox regression analysis. Discrimination and calibration were measured using the concordance index(c?index) and calibration plots.Results: Clinical and radiologic features were similar between the two groups. OS rates were significantly lower in the TACE group than in the TACE with H101 group(1?year OS rate, 53.8% vs. 61.3%; 2?year OS rate, 33.4% vs. 44.2%; 3?year OS rate, 22.4% vs. 40.5%; all P < 0.05). Multivariate Cox regression analysis for the entire cohort showed that alpha?fetoprotein level, alkaline phosphatase level, tumor size, metastasis, vascular invasion, and TACE with or without H101 were independent factors for OS, all of which were included in the nomogram. Calibration curves showed good agreement between nomogram?predicted survival and observed survival. The c?index of the nomogram for predict?ing OS was 0.716(95% confidence interval 0.686–0.746).Conclusions: TACE plus H101 extends the survival of patients with intermediate to advanced HCC. Our proposed nomogram provides individual survival prediction and stratification for patients with intermediate to advanced HCC who receive TACE with or without H101.

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).

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.

Transarterial radioembolization vs chemoembolization for hepatocarcinoma patients:A systematic review and metaanalysis

AIM: To compare the efficacy and safety of yttrium-90 radioembolization(Y90RE) and transarterial chemoembolization(TACE) in hepatocellular carcinoma patients. METHODS: Bibliographic research was conducted on main scientific databases. When there was no statistically significant heterogeneity, pooled effects were calculated using a fixed-effects model by means of Mantel-Haenszel test, otherwise, a random-effects model was used with Der Simonian and Laird test. Summary estimates were expressed in terms of odds ratios(ORs) and 95%CI. The probability of publication bias was assessed using funnel plots and with Begg and Mazumdar's test. Sensitivity analysis was finally conducted using the method of excluding extreme data.RESULTS: A total of 10 studies were analyzed, of which 2 randomized controlled trials. Survival rate(SR) assessed at 1 year showed an absolute similarity between the two treatment groups(OR = 1.01, 95%CI: 0.78-1.31, P = 0.93). As long as time elapsed since the treatment, ORs for survival rate tended to significantly increase, thus meaning better long-term outcomes in patients who underwent Y90RE(2-year SR: OR = 1.43, 1.08-1.89, P = 0.01; 3-year SR: OR = 1.48, 1.03-2.13, P = 0.04). Meta-analysis of plotted hazard ratios(HRs) determined a non-significant overall estimate in favor of Y90RE(HR = 0.91, 0.80-1.04, P = 0.16). Y90 RE showed a statistically significant benefit as compared to TACE in terms of higher progression-free survival rateassessed at 1 year(OR = 1.67; 95%CI: 1.10-2.55; P = 0.02). Pooled analyses do not revealed a statistically significant increase in OR for tumor objective responses after Y90 RE with respect to TACE(OR = 1.22, 95%CI: 0.69-2.16, P = 0.50). A non-significant trend in favor of Y90 RE was observed according to adverse event rate(OR = 0.70, 0.38-1.30, P = 0.26).CONCLUSION: Our meta-analysis reveals that Y90 RE and TACE show similar effects in terms of survival, response rate and safety profile, although tumor progression is delayed after radioembolization.

Transarterial chemoembolization with hepatic arterial infusion chemotherapy plus S-1 for hepatocellular carcinoma

BACKGROUND Transarterial chemoembolization(TACE)and hepatic arterial infusion chemotherapy(HAIC)have shown promising local benefits for advanced hepatocellular carcinoma(HCC).S-1,a composite preparation of a 5-fluorouracil prodrug,has proven to be a convenient oral chemotherapeutic agent with definite efficacy against advanced HCC.AIM To evaluate the efficacy and safety of TACE followed by HAIC with or without oral S-1 for treating advanced HCC.METHODS In this single-center,open-label,prospective,randomized controlled trial,117 participants with advanced HCC were randomized to receive TACE followed by oxaliplatin-based HAIC either with(TACE/HAIC+S-1,n=56)or without(TACE/HAIC,n=61)oral S-1 between December 2013 and September 2017.Two participants were excluded from final analysis for withdrawing consent.The primary endpoint was progression-free survival(PFS)and secondary endpoints included overall survival(OS),objective response rate,disease control rate and safety.RESULTS In total,115 participants(100 males and 15 females;mean age,57.7 years±11.9)were analyzed.The median PFS and OS were 5.0 mo(0.4–58.6 mo)(95%confidence interval(CI):3.82 to 6.18)vs 4.4 mo(1.1–54.4 mo)(95%CI:2.54 to 6.26;P=0.585)and 8.4 mo(0.4–58.6 mo)(95%CI:6.88 to 9.92)vs 8.3 mo(1.4–54.4 m)(95%CI:5.71 to 10.96;P=0.985)in the TACE/HAIC+S-1 and TACE/HAIC groups,respectively.The objective response rate and disease control rate were 30.9%vs 18.4%and 72.7%vs 56.7%in the TACE/HAIC+S-1 and TACE/HAIC groups,respectively.Grade 3/4 adverse events had a similar frequency in both treatment groups.CONCLUSION No improvements in tumor response rates,PFS or OS were observed with the addition of S-1 to TACE/HAIC in advanced HCC.Both treatment regimens had a similar safety profile.

“Six-and-twelve” score for outcome prediction of hepatocellular carcinoma following transarterial chemoembolization. In-depth analysis from a multicenter French cohort

The“six-and-twelve”(6&12)score is a new hepatocellular carcinoma(HCC)prognostic index designed for recommended transarterial chemoembolization(TACE)candidates.Quick and easy to use by the sum of tumor size(cm)and number,this model identifies three groups with different survival time(the sum is≤6;or>6 but≤12;or>12);a survival benefit with TACE can be expected for HCC patients with a score not exceeding twelve.Recently,Wang ZW et al showed that the“6&12”model was the best system correlated with radiological response after the first TACE.Thus,we wanted to assess its survival prediction ability as well as its prognostic value and compared it to other systems(Barcelona Clinic Liver Cancer,Hong Kong Liver Cancer(HKLC)staging,Albumin-Bilirubin grade,tumor nodularity,infiltrative nature of the tumor,alpha-fetoprotein,Child-Pugh class,and Performance Status score,Cancer of the Liver Italian Program,Model to Estimate Survival for HCC scores,up-to-seven criteria)different from Wang ZW et al study in a multicenter French cohort of HCC including only recommended TACE candidates retrospectively enrolled.As previously demonstrated,we show that the"6&12”score can classify survival within this French cohort,with a prognostic value comparable to that of other systems,except HKLC staging.More importantly,the“6&12”score simplicity and ability in patients’stratification outperform other systems for a routine clinical practice.

表柔比星、紫杉醇化疗辅助胃癌根治术患者血清HSP90α、CYFR211水平变化及预后影响因素分析

目的分析表柔比星联合紫杉醇化疗的胃癌根治术患者血清HSP90α、CYFR211水平及预后影响因素。方法选择胃癌根治术的患者96例,均采用表柔比星联合紫杉醇经动脉介入化疗。比较治疗前、治疗6周后、治疗12周后患者血清HSP90α、CYFR211水平。对患者随访2年,统计患者无进展生存时间(PFS)和总生存时间(OS),根据实体肿瘤WHO客观评价标准对患者预后进行评估,分为预后不良组和预后良好组,并通过单因素分析和多因素logistic回归分析影响胃癌根治术患者预后的危险因素。结果治疗6周后,2组患者血清HSP90α、CYFR211水平较治疗前低(P<0.05),治疗12周后,2组患者血清HSP90α、CYFR211水平较治疗前及治疗6周后低(P<0.05)。患者6个月、1年、2年无进展生存率分别为58.3%、30.2%、20.2%,6个月、1年、2年总生存率分别为81.2%、63.5%、32.6%,中位PFS和OS分别为10个月、16个月。单因素分析显示:胃癌根治术患者的预后与性别、体质指数、手术出血量、手术方式、术后是否出现严重不良反应、胃癌发生部位无关(P>0.05),而与年龄、肿瘤直径、手术时间、胃切除范围、TNM分期、肿瘤分化程度有关(P<0.05);多因素分析显示,年龄、肿瘤直径、胃切除范围、手术时间、TNM分期、肿瘤分化程度是影响胃癌根治术患者预后不良的独立危险因素(P<0.05)。结论表柔比星联合紫杉醇经动脉介入化疗治疗胃癌根治术患者,可以降低血清HSP90α、CYFR211水平,疗效尚可。年龄、肿瘤直径、胃切除范围、手术时间、TNM分期、肿瘤分化程度是胃癌根治术患者预后的独立影响因素。

ALT/AST及影像学特征预测肝癌经动脉化疗栓塞患者的预后

目的探讨经动脉化疗栓塞(transarterial chemoembolization,TACE)治疗前血清丙氨酸转氨酶/天冬氨酸转氨酶比值(ALT/AST)及影像学特征与肝癌患者预后的关系,构建预测患者总体生存率(overall survival,OS)的诺模图模型。方法纳入2016年7月至2020年7月苏州大学附属第一医院广慈分院诊断为肝癌并以TACE作为初始治疗的患者211例,将其随机分为建模组139例,验证组72例。采用受试者工作特征(receiver operation characteristics,ROC)曲线确定AST/ALT的最佳临界值。在建模组患者中进行单、多因素Cox回归分析,筛选影响肝癌患者OS的独立预测因素并构建预后模型。通过Harrell一致性指数(C指数)评价诺模图对肝癌患者OS的预测能力,校准曲线用于评估预后模型的预测准确性。结果建模组与验证组患者的基线特征分布差异均无统计学意义(均P>0.05)。两组患者中位OS分别为28.5个月(95%CI:22.1~34.9)和25.1个月(95%CI:19.2~29.0),差异无统计学意义(χ^(2)=1.395,P=0.322)。AST/ALT预测肝癌患者OS的最佳临界值为1.10,曲线下面积(area under curve,AUC)为0.674(95%CI:0.604~0.753)。Cox回归分析表明,肿瘤个数(HR=2.080,95%CI:1.245~3.475,P=0.005)、肿瘤包膜(HR=1.771,95%CI:1.128~2.780,P=0.013)、不规则边缘强化(HR=1.884,95%CI:1.190~2.984,P=0.007)和AST/ALT(HR=2.450,95%CI:1.506~3.987,P<0.01)是接受TACE治疗肝癌患者的独立预后因素。基于以上变量构建预测OS的诺模图模型,其在建模组与验证组中的C指数分别为0.733(95%CI:0.650~0.826)和0.770(95%CI:0.688~0.862)。校准曲线显示预后模型对1、2和3年OS的预测曲线与理想参考线之间未见明显偏离。结论基于肿瘤个数、影像学特征及AST/ALT的诺模图对接受TACE治疗的肝癌患者预后显示了良好的预测价值。

基于术前炎症指标构建和验证肝癌患者TACE治疗预后的列线图

目的构建并验证基于术前炎症生物标志物的预测模型,评估其对不可切除肝癌患者行TACE治疗的预后预测能力。方法 回顾性收集2007年1月至2020年12月在六家医疗机构接受TACE作为初始治疗的544例患者,并拆分为训练集和验证集。使用LASSO算法和Cox回归筛选独立影响因素并建模。从区分度、校准度和临床适用性对模型进行验证,绘制Kaplan-Meier风险分层曲线确定组间预后差异,计算模型的似然比卡方值、R2值、AIC值、C指数以及AUROC值评估模型的准确性和效能。结果 训练集和验证集分别为376例和168例。多因素分析显示BCLC分级、肿瘤大小、肿瘤数量、中性粒细胞和预后营养指数(prognostic nutritional index,PNI)是患者术后总生存期(OS)的独立影响因素(P<0.05);BCLC分级、肿瘤大小、肿瘤数量、NLR、PNI和PS评分是患者无进展生存期(PFS)的独立影响因素(P<0.05)。OS和PFS模型的C指数分别为0.735(95%CI:0.708~0.762)和0.736(95%CI:0.711~0.761),外部验证为0.721(95%CI:0.680~0.762)和0.693(95%CI:0.656~0.730)。列线图的时间依赖性C指数、时间依赖性ROC曲线和时间依赖性AUC曲线均显示出理想的区分能力。校准曲线与理想标准线明显重合,表明模型稳定性高,过拟合程度低。决策曲线分析揭示了更大范围的阈值概率,可以增加净收益。KaplanMeier曲线显示不同风险组患者的预后差异显著(P<0.000 1)。模型的似然比卡方值、R2值、AIC值、C指数以及AUROC值均优于目前临床常用的其他模型。结论 基于术前炎症标志物所构建的列线图在预测TACE预后方面表现出优秀的准确性和出色的预测效率,可以作为指导个体化治疗和预测预后的有效工具。

Sequential or simultaneous transarterial chemoembolization and radiofrequency ablation for hepatocellular carcinoma within the Milan criteria:A retrospective real-world study

Aims:Few studies have investigated differences in sequential transarterial chemoembolization(TACE),radiofrequency ablation(RFA),and simultaneous RFA-TACE for the treatment of hepatocellular carcinoma(HCC)using the Milan criteria.This study explored the differences in safety and prognosis between sequential TACE-RFA and simultaneous RFA-TACE.Methods:This retrospective real-world study included 109 patients with HCC within the Milan criteria who underwent sequential TACE-RFA(n=75)or simultaneous RFA-TACE(n=34)at the Eastern Hepatobiliary Surgery Hospital between January 2017 and 2021.Postoperative complications,length of hospital stay,and long-term prognosis were compared.The median follow-up duration of these patients was 39.1 months.Overall survival(OS)and time to tumor recurrence(TTR)curves were plotted using the Kaplan−Meier method and were compared using the logarithmic rank test.Independent risk factors for OS and tumor recurrence(TR)were analyzed using the Cox risk regression model.Results:Multivariate analysis showed that tumor diameter>3 cm(hazard ratio[HR]:2.201,95%confidence interval[CI]:1.106-4.378,p=0.025;HR:2.236,95%CI:1.271-3.934,p=0.005,respectively)and alphafetoprotein(AFP)>400μg/L(HR:2.362,95%CI:1.195-4.668,p=0.013;HR:1.798,95%CI:1.048-3.086,p=0.033,respectively)were independent risk factors for OS and TTR,whereas the presence of multiple tumors(HR:2.352,95%CI:1.127-4.907,p=0.023)was an independent risk factor for TTR.Simultaneous RFA-TACE did not have an effect on OS or TTR.After propensity score-matched,comparable results were obtained and RFATACE still had no effect on OS or TTR.No significant differences were observed in grade III/IV complications(2/75[2.7%]vs.1/34[2.9%],p=1.000)between the two groups.However,the RFA-TACE group had fewer complications than the TACE-RFA group(24/34[70.6%]vs.66/75[88.0%],p=0.026).The RFA-TACE group had a shorter hospital stay and less total cost during hospitalization compared with the TACE-RFA group(6.0 vs.10.0 days,p<0.001;30,000 vs.35,000 CNY,p<0.001).Conclusions:For HCC within the Milan criteria,there was no significant difference in OS and TTR between RFA-TACE and TACE-RFA.However,RFA-TACE could reduce all-grade complications and shorten the length of hospital stay compared with TACE-RFA.Therefore,simultaneous RFA-TACE may be considered for patients with HCC and good liver function falling within the Milan criteria.

Actuality and underlying mechanisms of systemic immuneinflammation index and geriatric nutritional risk index prognostic value in hepatocellular carcinoma

This editorial contains comments on the article“Correlation between preoperative systemic immune inflammation index,nutritional risk index,and prognosis of radical resection of liver cancer”in a recent issue of the World Journal of Gastrointestinal Surgery.It pointed out the actuality and importance of the article and focused primarily on the underlying mechanisms making the systemic immuneinflammation index(SII)and geriatric nutritional risk index(GNRI)prediction features valuable.There are few publications on both SII and GNRI together in hepatocellular carcinoma(HCC)and patient prognosis after radical surgery.Neutrophils release cytokines,chemokines,and enzymes,degrade extracellular matrix,reduce cell adhesion,and create conditions for tumor cell invasion.Neutrophils promote the adhesion of tumor cells to endothelial cells,through physical anchoring.That results in the migration of tumor cells.Pro-angiogenic factors from platelets enhance tumor angiogenesis to meet tumor cell supply needs.Platelets can form a protective film on the surface of tumor cells.This allows avoiding blood flow damage as well as immune system attack.It also induces the epithelial-mesenchymal transformation of tumor cells that is critical for invasiveness.High SII is also associated with macro-and microvascular invasion and increased numbers of circulating tumor cells.A high GNRI was associated with significantly better progression-free and overall survival.HCC patients are a very special population that requires increased attention.SII and GNRI have significant survival prediction value in both palliative treatment and radical surgery settings.The underlying mechanisms of their possible predictive properties lie in the field of essential cancer features.Those features provide tumor nutrition,growth,and distribution throughout the body,such as vascular invasion.On the other hand,they are tied to the possibility of patients to resist tumor progression and development of complications in both postoperative and cancer-related settings.The article is of considerable interest.It would be helpful to continue the study follow-up to 2 years and longer.External validation of the data is needed.

PA-TACE的时机选择对肝细胞癌患者根治性切除术后近期预后的影响

目的探讨肝癌根治性切除术后辅助性肝动脉化疗栓塞(PA-TACE)治疗的时机选择对肝细胞癌(HCC)患者近期预后的影响。方法回顾性分析南京医科大学附属无锡人民医院2015年1月至2021年12月收治的103例肝癌根治性切除术后半年内接受TACE治疗的HCC患者的临床资料,根据术后接受TACE治疗的时间不同,分为观察组(n=53)和对照组(n=50)。观察组患者在术后4~8周接受TACE治疗,对照组患者在术后9~26周接受TACE治疗。肝癌根治性切除术后随访2年。对两组患者术后2年复发率、2年生存率进行比较,同时比较TACE治疗期间两组患者不良反应的发生率,以及术后2年两组患者在各项评估量表指标上的差异。结果与对照组相比,观察组患者肝癌根治性切除术后2年复发率较低[20.8%(11/53)vs 48.0%(24/50),χ^(2)=7.429,P=0.006],术后2年生存率较高[88.7%(47/53)vs 78.0%(39/50),χ^(2)=5.316,P=0.021],差异具有统计学意义(P<0.05);TACE治疗期间,两组患者不良反应的总发生率差异无统计学意义(χ^(2)=0.160,P>0.05);肝癌根治性切除术后2年,与对照组相比,观察组患者的PS评分、Child-Pugh评分、PS-SGA评分、FPS-R评分均较低,但差异均无统计学意义(P>0.05);观察组患者生活质量评分较对照组高,差异具有统计学意义(t=7.236,P<0.05)。结论HCC患者在肝癌根治性切除术后4~8周内接受PA-TACE治疗,能减少术后早期肿瘤复发率,提高生存率,提高患者手术后的生活质量。

Nomogram model based onγ-glutamyl transferase to albumin ratio predicts survival in hepatocellular carcinoma patients with transarterial chemoembolization treatment

BACKGROUND The development of tumor is closely linked to inflammation.Therefore,targeting molecules involved in inflammation may be effective in predicting cancer prognosis.Transarterial chemoembolization(TACE)holds significant therapeutic significance in addressing hepatocellular carcinoma(HCC).At present,no studies have evaluated the predictive value ofγ-glutamyl transferase to albumin ratio(GAR)on the prognosis of HCC undergoing TACE.AIM To explore the potential prognostic significance of the GAR in individuals undergoing TACE for HCC.METHODS A total of 1231 patients from seven hospitals in China were randomized into a training cohort(n=862)and a validation cohort(n=369).To establish inde pendent prognostic factors for overall survival(OS),we utilized multivariate and univariate Cox regression models.The best cut-off value of the GAR was determined with the X-tile software,with OS as the basis.Validations were performed using dual therapy cohort and triple therapy cohort.RESULTS X-tile software revealed a GAR threshold of 4.75 as optimal.Both pre-and post-propensity score matching analyses demonstrated that the median OS in the low-GAR group(<4.75)was notably longer compared to the high-GAR group(≥4.75),showing results of 26.9 vs 9.8 months(P<0.001)initially,and 18.1 vs 11.3 months(P<0.001)after match.Furthermore,multivariate analysis identified GAR≥4.75 as an independent prognostic factor(P<0.001).The receiver operating characteristic curves for the nomogram showed area under receiver operating characteristic curves of 0.741,0.747,and 0.708 for predicting 1-,2-,and 3-year survival,respectively.Consistent findings were reiterated in the two cohorts involving TACE in combination with targeted therapy and TACE in combination with targeted therapy and immunotherapy.Calibration curve and decision curve analyses substantiated the model’s relatively robust predictive capabilities.CONCLUSION Our study validates the effective prognostic capacity of the GAR-based nomogram for HCC patients undergoing TACE or TACE in combination with systemic therapy.

核苷(酸)类似物抗病毒治疗HBV相关肝细胞癌患者低病毒血症及其对肿瘤治疗疗效的影响

目的分析核苷(酸)类似物(NAs)抗病毒治疗乙型肝炎病毒(HBV)相关肝细胞癌(HCC)患者发生低病毒血症(LLV)及其对肿瘤治疗疗效的影响。方法2016年1月~2020年12月我院收治的HBV相关HCC初治患者119例,所有患者均接受肝动脉化疗栓塞术(TACE)及其综合抗肿瘤治疗,给予恩替卡韦(ETV)或富马酸替诺福韦二吡呋酯抗病毒治疗。随访截止时间为2021年12月31日。结果在119例HBV相关HCC患者中,有42例(35.3%)抗病毒后发生LLV;LLV组血清HBeAg阳性率为64.3%,显著高于非LLV组的27.3%(P<0.05);在治疗后3个月,LLV组肿瘤客观缓解率(ORR)为33.3%,显著低于非LLV组的58.4%(P<0.05);在治疗后6个月,LLV组血清ALT、AST、Child-Pugh评分和甲胎蛋白(AFP)水平分别为35.0(28.6,56.0)U/L、56.0(43.6,78.5)U/L、7.0(6.0,8.0)分和2732.0(85.7,17595.0)ng/ml,显著高于非LLV组【分别为29.0(21.0,43.0)U/L、40.0(27.0,61.0)U/L、6.0(5.0,7.0)分和22.5(5.2,780.6)ng/ml,P<0.05】;LLV组2 a生存率为2.4%,显著低于非LLV组的41.6%(P<0.05);Logistic回归分析显示,是否存在LLV【HR(95%CI)为2.1(1.3~3.3)】、巴塞罗那(BCLC)分期【HR(95%CI)为1.7(1.2~1.9)】和射频消融术(RFA)【HR(95%CI)为0.4(0.2~0.7)】是影响HBV相关HCC患者预后的独立因素(P<0.05)。结论HBeAg阳性可能是HBV相关HCC患者NAs治疗后发生LLV的影响因素,而LLV可能影响抗肿瘤治疗疗效,值得重视。

辅助性经肝动脉化疗栓塞对肝内胆管癌患者根治术后预后的影响

目的评估肝内胆管癌(intrahepatic cholangiocarcinoma,ICC)根治性切除术后行辅助性经肝动脉化疗栓塞(transcatheter arterial chemoembolization,TACE)治疗对患者生存及肿瘤复发的影响。方法本研究收集2010年1月—2015年12月在东方肝胆外科医院完成根治性切除术的ICC患者,按是否接受术后辅助性TACE,分为TACE组(术后接受辅助TACE)和非TACE组(术后未接受辅助TACE)。根据美国癌症联合委员会(AJCC)第8版肿瘤TNM分期系统进行分期。单因素及多因素分析用于评估独立的预后因素。Kaplan-Meier方法比较无复发生存率(RFS)和总生存率(OS)。结果共有599例ICC患者纳入本研究,TACE组115例,非TACE组484例,中位随访时间为23个月。TACE组和非TACE组的1、3、5年OS生存率分别为67.0%、51.8%、36.6%和67.2%、48.5%、35.9%,两组患者生存时间比较,差异无统计学意义(P=0.5929);TACE组的中位RFS时间要明显短于非TACE组(6个月vs 11个月),TACE组和非TACE组的1、3、5年RFS生存率分别为32.3%、24.0%、18.8%,和46.1%、33.4%、25.8%,两组比较,差异具有统计学意义(P=0.0036)。Cox回归模型显示,TACE组与非TACE组ICC患者无复发生存率存在统计学差异(HR=1.51,95%CI:1.151.96;P=0.0026)。结论ICC患者根治性切除术后辅助性TACE不能延长ICC患者的总生存率,而且可能有增加ICC术后患者肿瘤复发的风险。

老年营养风险指数与肝细胞癌经动脉化疗栓塞术患者长期预后的关联和临床价值

目的分析老年营养风险指数(GNRI)与肝细胞癌经动脉化疗栓塞术(TACE)患者长期预后的关联和临床价值。方法选取2016年6月至2019年5月在中国人民解放军总医院第一医学中心行TACE的肝细胞癌患者120例,按照3年生存情况分为生存组34例和死亡组86例。比较两组的临床资料,采用生存函数Cox回归分析临床资料对肝细胞癌TACE患者长期预后的影响,并采用Spearman分析GNRI与肝细胞癌TACE患者长期预后的关联。结果死亡组年龄(74.29±2.30)岁明显高于生存组(71.40±3.29)岁(P<0.05),死亡组GNRI(88.36±3.69)明显低于生存组(92.42±3.54)(P<0.05),死亡组肿瘤最大径、肝硬化、远处转移、脉管瘤栓与对照组比较,差异均有统计学意义(P<0.05)。死亡组性别、乙型肝炎病毒表面抗原(HB-sAg)、丙型肝炎病毒(HCV)、TNM分期、肿瘤部位、肝功能Child-Pugh分级、肿瘤数目、术前甲胎蛋白(AFP)、腹水、侵及肝被膜、冠心病、高血压、扩张型心肌病、糖尿病、心房颤动、既往脑卒中、高脂血症、吸烟史、饮酒史、TACE治疗次数与生存组比较,差异均无统计学意义(P﹥0.05)。经Cox回归分析,年龄大、肝硬化是肝细胞癌TACE患者死亡的影响因素(P<0.05),GNRI高是肝细胞癌TACE患者死亡的保护因素(P<0.05)。经Spearman分析,肝细胞癌TACE患者GNRI与预后呈负相关(P<0.05)。结论年龄大、肝硬化、GNRI低是TACE患者死亡的危险因素,GNRI和TACE患者预后可能具有一定关联,早期评估GNRI能够为有效预测患者预后提供科学依据。

肝动脉化疗栓塞联合索拉菲尼治疗中晚期肝细胞癌

目的探讨肝动脉化疗栓塞(TACE)联合索拉菲尼治疗中晚期肝细胞癌(HCC)的临床价值。方法前瞻性分析我院2011年1月至2012年1月接受TACE联合索拉菲尼(n=27)和TACE单独治疗(n=25)的中晚期HCC患者的临床资料,比较两组患者肿瘤中位进展时间、肿瘤无进展生存率和总生存率。结果随访期间,联合治疗组共发生肿瘤进展18例,死亡10例,疾病控制率为74.1%;TACE单独治疗组共发生肿瘤进展19例,死亡15例,疾病控制率为68.0%。联合治疗组和TACE单独治疗组肿瘤中位进展时间分别为6.5个月和3.3个月(P<0.05),两组6和12个月的肿瘤无进展生存率分别为51.9%、33.3%和27.6%、16.5%(P<0.05),总生存率分别为81.0%、60.8%和63.3%、34.8%(P<0.05)。联合治疗组的手足皮肤反应、口腔黏膜炎发生率较TACE单独治疗组高(P<0.05),药物减量辅以对症治疗后控制良好。结论 TACE联合索拉菲尼治疗中晚期HCC是安全有效的,优于TACE单独治疗,值得临床进一步验证推广。