Adjuvant Transarterial Chemoembolization Following Liver Resection for Intrahepatic Cholangiocarcinoma Based on Survival Risk Stratification

Background.

The effectiveness of adjuvant transarterial chemoembolization (TACE) for intrahepatic cholangiocarcinoma (ICC) after hepatectomy remains unclear. This study was performed to identify ICC patients who would benefit from adjuvant TACE.

Patients and Methods.

The study included 553 patients who underwent hepatectomy for ICC between January 2008 and February 2011 at the Eastern Hepatobiliary Surgery Hospital and who were treated with or without TACE (122 with TACE and 431 without TACE). Survival risk stratification was performed using the established prognostic nomogram (ICC nomogram). The predictive performance was evaluated by concordance index and calibration. The tumor recurrence and overall survival (OS) rates were analyzed by the Kaplan-Meier method before and after propensity score matching (PSM).

Results.

The predictive performance of the ICC nomogram was demonstrated by the well-fitted calibration curves and an optimal c-index of 0.71 for OS prediction. In the whole cohort, the 5-year recurrence and OS rates between the TACE and non-TACE groups were significantly different (5-year recurrence: 72.9% vs. 78.1%; OS: 38.4% vs. 29.7%). After 1:1 PSM, the TACE and non-TACE groups (122 patients each) had similar 5-year recurrence and OS rates (5-year recurrence: 72.9% vs. 74.2%; OS: 38.4% vs. 36.0%). By survival risk stratification based on ICC nomogram, only the patients in the lowest tertile (nomogram scores ≥77) benefited from adjuvant TACE (TACE vs. non-TACE groups: 90.4% vs. 95.9% for 5-year recurrence; 21.3% vs. 6.2% for 5-year OS).

Conclusion.

Adjuvant TACE following liver resection might be suitable for ICC patients with high ICC nomogram scores (≥77).

Implications for Practice:

The accurate predictive performance of the established prognostic nomogram for intrahepatic cholangiocarcinoma (ICC) following liver resection was reconfirmed in an independent cohort with 553 patients. Based on the survival risk stratification using the nomogram, adjuvant transarterial chemoembolization following liver resection might be suitable only for ICC patients with high scores from the nomogram.     

Development of a prognostic score for recommended transarterial chemoembolization candidates with spontaneous rupture of hepatocellular carcinoma

BackgroundAlthough transarterial chemoembolization (TACE) has been widely used for treating the spontaneous rupture of hepatocellular carcinoma (HCC), no existing model exists for predicting survival. The aim of this study was thus to develop and validate a nomogram for estimating the prognosis in patients with ruptured HCC upon undergoing TACE treatment.MethodsThis study included 55 patients with spontaneously ruptured HCC who underwent TACE treatment between January 2015 and April 2019. The diagnosis of spontaneous HCC rupture was based on the disruption of the peritumoral liver capsule with surrounding fluid in the perihepatic region. The prognostic nomogram was constructed using the independent predictors assessed by the multivariate Cox proportional hazards model.ResultsThe median overall survival (OS) was 6.4 months, with 6-month and 1-year survival rates of 52.7% and 41.8%, respectively. In the univariate analysis, the size of the largest tumor, total bilirubin (TBIL) levels, and aspartate aminotransferase (AST) levels were associated with the OS of patients. Multivariate analysis suggested that TBIL levels (HR =0.358, P=0.036) and diameter of the largest tumor (HR =1.012, P=0.044) were independent prognostic factors for predicting the OS. Based on these variables, we developed and validated a nomogram for the risk stratification of HCC rupture after TACE treatment for individual patients. According to the nomogram risk assessment, we were able to evaluate the approximate 1- and 2-year survival rates based on patients’ tumor diameter and TBIL level after TACE treatment of ruptured HCC. The concordance index for the OS prediction was 0.748 (95% CI: 0.691–0.805). This newly developed nomogram represents an intuitive tool for predicting the OS of patients with ruptured HCC.ConclusionsThis study indicated that TBIL levels and diameter of the largest tumor were independent prognostic factors for predicting the OS of ruptured HCC. This study may help maximize favorable TACE treatment outcomes.     

The Prognosis of Hepatocellular Carcinoma Treated with Sorafenib in Combination with TACE

Objective: Sorafenib have been shown to be effective in the treatment of advanced HCC and has been standard therapy since its release in Japan in 2009 (Llovet et al., 2008; Cheng et al., 2009). However, due to a low response rate, more aggressive combination treatment has been utilized as a multimodal strategy. The present study aimed to determine the efficacy of sorafenib alone and in combination with transarterial chemoembolization (TACE) for the treatment of advanced HCC. Methods: All patients with unresectable advanced HCC who were prescribed sorafenib at Kanto Rosai Hospital were included in the study. Five-year overall survival (OS) rates were estimated for patients treated with sorafenib alone or in combination with TACE. Multivariate and univariate regression analyses were performed to identify factors affecting OS. Analysis using propensity score matching and inverse-probability weights were also performed. Results: A total of 46 patients were treated with sorafenib up to June 2018. The total sorafenib dose administered was higher in the TACE combination group (70900 mg vs. 24000 mg vs. with sorafenib alone), although the relative dose intensity was lower (11.7% vs. 17.6%, respectively). The 5-year survival prognosis estimated using the Kaplan-Meier method was longer in patients treated with sorafenib in combination with TACE versus sorafenib alone (36.3% vs. 7.7%). Combination with TACE was the only factor associated with improved OS in both univariate and multivariate analysis. Among cases matched by propensity scores the hazard rate for combination with TACE was 0.067 (95% CI 0.091-1.128). Conclusion: With an array of therapeutic options currently available, it is important to determine the efficacy of different multimodal strategies, such as sorafenib combined TACE, for patients with unresectable HCC.     

碱性磷酸酶和淋巴细胞比值在评估BCLC分级A-B级肝癌患者TACE术后生存情况的应用价值

目的:探讨碱性磷酸酶和淋巴细胞比值(ALR)在预测巴塞罗那（BCLC）分级A-B级肝癌患者肝动脉灌注化疗栓塞术（TACE）术后生存情况的价值。方法:以肝癌TACE术后肿瘤进展或死亡为状态变量,分别以中性粒细胞和淋巴细胞比值、淋巴细胞和单核细胞比值、碱性磷酸酶、淋巴细胞计数以及ALR作为检验变量,进行两者的ROC分析,根据术前ALR预测肝癌患者TACE术后肿瘤进展或死亡的最佳诊断截点将所有纳入患者分为A组和B组,对两组肝癌患者通过倾向性评分匹配法进行配对分组,通过logistic回归估计倾向性评分值,检验匹配后两组临床病理指标的均衡性,匹配后标准差异绝对值均控制在 0.10以内,Kaplan-Meier生存分析分别比较匹配后A组和B组两组肝癌患者TACE术后无进展生存率和总生存率,采用Cox 回归分析评价匹配前后ALR对肝癌患者TACE术后PFS和OS的预测价值。结果:根据ALR最佳诊断截点将纳入所有患者分为ALR<5.4×10-7(A组)和ALR≥5.4×10-7(B组),通过倾向性评分匹配,两组共 57对匹配成功,匹配前两组间有显著性差异的临床指标经匹配后均达到平衡,其他无显著性差异的指标均衡性也得到了明显的提高,Kaplan-Meier生存分析显示,匹配后A组肝癌患者TACE术后1年、2年、3年无进展生存率显著高于B组(60.5%、41.2%、33.6% vs 47.9%、20.9%、20.9%,P＜0.05),A组肝癌患者TACE术后1年、2年、3年总生存率显著高于B组(72.3%、62.4%、55.2% vs 63.5%、51.5%、31.8%,P＜0.05),Cox回归分析显示,匹配前后ALR均为肝癌患者TACE术后PFS和OS的独立预测因素。结论:术前ALR水平预测BCLC分级A-B级肝癌患者TACE术后远期生存情况具有较高的价值。     

高强度聚焦超声联合动脉栓塞化疗治疗晚期肝癌的初步临床研究

目的　探讨高强度聚焦超声 (HIFU)联合经动脉栓塞化疗 (TACE)治疗晚期肝癌的有效性。方法　 5 0例不能手术切除的晚期肝癌患者 (TNM分期Ⅳ期 )随机分为两组 :(1)单纯TACE组 2 6例 ;(2 )HIFU联合TACE组 2 4例 ,在TACE治疗后 2～ 3周 ,接受HIFU治疗。全部患者随访 3～ 2 4个月 ,平均 (8.16± 2 .79)个月。应用Kaplan Meier等统计学方法分别比较了两组患者的中位生存时间、6个月和 1年生存率、死亡患者平均生存时间。结果　HIFU联合TACE治疗组患者的中位生存时间为11.3个月 ,6个月和 1年生存率分别为 80 .4 %～ 85 .4 %和 4 2 .9% ;而TACE治疗组患者的中位生存时间为 4个月 ,6个月和 1年生存率分别为 13.2 %和 0 % ,两组比较 ,差异有显著性 (P <0 .0 1)。HIFU联合TACE治疗组死亡患者的平均生存时间为 (10 .2 1± 4 .12 )个月 ,而TACE组患者为 (4 .35± 2 .39)个月 ,两组比较 ,差异有显著性 (P <0 .0 1)。结论　HIFU联合TACE治疗晚期肝癌患者的疗效明显优于单纯TACE ,此联合治疗有望成为不能手术切除肝癌的一种有效手段。     

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.     

中性粒细胞/淋巴细胞比值血小板/淋巴细胞比值与TACE治疗肝癌患者预后的相关性

  目的  本研究探讨中性粒细胞与淋巴细胞比值（neutrophil to lymphocyte ratio,NLR）和血小板与淋巴细胞比值（platelet to lymphocyte ratio,PLR）与接受肝动脉栓塞化疗（transarterial chemoembolization,TACE）肝癌（hepatocellular carcinoma,HCC）患者术后生存期的相关性。  方法  回顾性分析2007年1月至2015年6月中山大学肿瘤防治中心肝胆胰科确诊为肝癌并行TACE治疗的216例患者。研究患者依照NLR和PLR的界值分成两组。分析并比较NLR和PLR在不同随访时间点的受试者工作曲线（ROC）下面积。单因素和多因素分析用于评价NLR和PLR与TACE术后肝癌患者预后的相关性。  结果  本研究中位随访时间为431.1 d。全体研究对象1、2、3年生存率分别为61.3%、44.2%和40.5%。中位生存时间为410.5 d。术前NLR＜1.77组和术前NLR≥1.77组1、2、3年生存率分别为81.6%、63.0%、45.7%和43.1%、27.0%、19.3%,差异具有统计学意义（P < 0.001）。术前PLR < 94.62组和术前PLR≥94.62组1、2、3年生存率分别为62.7%、47.0%、37.0%和46.8%、29.0%、18.5%,差异具有统计学意义（P=0.002）。多因素分析显示NLR≥1.77与TACE术后肝癌患者较差预后相关,是肝癌患者TACE治疗后的危险因素。  结论  TACE介入术前HCC患者的NLR水平,作为系统炎症的一个反应指标,是影响其预后的危险因素。      

Development and validation of a nomogram for predicting the survival of patients with non-metastatic nasopharyngeal carcinoma after curative treatment

Background:The TNM staging system is far from perfect in predicting the survival of individual cancer patients because only the gross anatomy is considered. The survival rates of the patients who have the same TNM stage disease vary across a wide spectrum. This study aimed to develop a nomogram that incorporates other clinicopatho-logic factors for predicting the overall survival (OS) of non-metastatic nasopharyngeal carcinoma (NPC) patients after curative treatments. Methods:We retrospectively collected the clinical data of 1520 NPC patients who were diagnosed histologically between November 2000 and September 2003. The clinical data of a separate cohort of 464 patients who received intensity-modulated radiation therapy (IMRT) between 2001 and 2010 were also retrieved to examine the extensibil-ity of the model. Cox regression analysis was used to identify the prognostic factors for building the nomogram. The predictive accuracy and discriminative ability were measured using the concordance index (c-index). Results:We identiifed and incorporated 12 independent clinical factors into the nomogram. The calibration curves showed that the prediction of OS was in good agreement with the actual observation in the internal validation set and IMRT cohort. The c-index of the nomogram was statistically higher than that of the 7th edition TNM staging sys-tem for predicting the survival in both the primary cohort (0.69 vs. 0.62) and the IMRT cohort (0.67 vs. 0.63). Conclusion:We developed and validated a novel nomogram that outperformed the TNM staging system in predict-ing the OS of non-metastatic NPC patients who underwent curative therapy.     

肝动脉栓塞化疗联合肝复乐治疗晚期肝癌临床疗效观察(英文)

Objective: The aim of this study was to evaluate the efficacy of transcatheter arterial chemoembolization (TACE) combined with a Chinese compound preparation of ganfule on advanced hepatocellular carcinoma (HCC). Methods: The study population consisted of 132 advanced HCC patients with Child-pugh A/B. Tumor in all patients was involved with main trunk of portal vein and/or inferior vena cava, or local lymph node metastasis, or distant metastasis. TACE combined with ganfule were performed in 65 patients with advanced HCC (interventional treatment group), 67 patients were treated with traditional Chinese herbal drug alone (Chinese herb group). The prime end point was overall survival (OS), and prognostic factors were analyzed. Results: The median OS was 205 days [95% confidence interval (CI), 155-255 days] in interventional treatment group and 127 days (95% CI, 70-184 days) in Chinese herb group (P<0.05). The 6-month, 1-year, and 2-year OS rates were 58.9%, 29.1%, 7.7% in interventional treatment group, and 33.3%, 12.3%, 1.8% in Chinese herb group, respectively. The portal vein thrombosis, ECOG performance status (PS) were independent prognostic factors for OS. Conclusion: Ttranscatheter arterial chemoembolization combined with a Chinese compound preparation of ganfule could greatly prolong the OS of advanced HCC patients. The portal vein thrombosis and ECOG PS were independent prognostic factors for OS.     

The safety and efficacy of TACE combined with apatinib on patients with advanced hepatocellular carcinoma: a retrospective study

As a novel vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor (VEGFR2-TKI), apatinib has a certain anti-tumor effect for a variety of solid tumors. The present study evaluates its efficacy and safety in advanced hepatocellular carcinoma (HCC). In this study, 47 patients with advanced HCC were included. TACE monotherapy group included 22 patients that responded to TACE, while the group that received TACE and apatinib included 25 patients that progressed on TACE and were able to receive apatinib off label. Median overall survival (OS) was significantly improved in the apatinib plus TACE group compared with the TACE group. Similarly, apatinib in combination with TACE significantly prolonged median progression-free survival (PFS) compared with TACE monotherapy. Furthermore, there was a significant difference between combination therapy and monotherapy in both Barcelona clinic liver cancer (BCLC) B and BCLC C group. The combination therapy had a dramatic effect on OS and PFS for patients at both BCLC B and BCLC C level. The most common clinically adverse events of apatinib plus TACE group were fatigue, weight loss, hypertension, hand-foot syndrome and anorexia, which were manageable and tolerable. The efficacy analysis showed that there was no significant association of survival benefit with age, gender, Eastern Cooperative Oncology Group (ECOG) performance status, hypertension and hand-foot syndrome. Patients with macrovascular invasion and extrahepatic invasion showed worse survival benefits. In conclusion, apatinib combined with TACE revealed certain survival benefits for HCC patients who experienced progression following TACE, which can provide a promising strategy for HCC treatment.     

PCNA在接受过术前经导管肝动脉栓塞化疗的肝癌组织中的表达及其预后意义

背景与目的:增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)可反映肝细胞癌(以下简称"肝癌")的增殖活性,经导管肝动脉栓塞化疗(transcatheter arterial chemoembolization,TACE)对术后残癌细胞增殖活性影响的报道结果不一。本研究旨在探讨术前TACE对肝癌增殖活性的影响和PCNA在二期切除肝癌复发预后中的意义。方法:选取91例术前TACE及50例未行TACE的肝癌手术切除标本,采用免疫组化方法检测两组标本PCNA的表达情况,分层分析两组PCNA表达的差异,以及术前TACE后二期根治性切除的肝癌中PCNA的表达水平与复发的关系。结果:PCNA表达于肝细胞核中,术前TACE组和未行TACE组的PCNA阳性率分别为67.0%和66.0%(P>0.05),术前TACE组中癌栓、播散结节或肿瘤低分化(Ⅲ～Ⅳ级)者PCNA的表达均明显低于对应分层的未行TACE者,差异有统计学意义(P<0.05)。术前TACE后根治性二期切除患者,复发组与未复发组肿瘤组织中PCNA阳性率分别为77.8%、47.1%,差异有统计学意义(P<0.05)。PCNA阳性组1、3、5年无瘤生存率分别为55.8%、31.8%、23.6%,PCNA阴性组分别为83.2%、62.1%、53.2%,差异有统计学意义(P<0.05)。结论:术前TACE对高侵袭肝癌细胞增殖活性有较好的抑制作用,术前TACE后二期根治性切除肝癌PCNA的表达与患者术后复发转移密切相关。     

Preoperative serum fibrinogen as a valuable predictor in the nomogram predicting overall survival of postoperative patients with gallbladder cancer

BackgroundCoagulation and fibrinolysis activation are frequently observed in cancer patients, and the tumors in these cases are thought to be associated with a higher risk of invasion, metastasis and worse long-term outcome. The specific aim of this study was to develop an effective prognostic nomogram to help make individualized estimates for patients with resected gallbladder cancer (GBC).MethodsPatients with resected GBC who were diagnosed between 2006 and 2014 at Xinhua Hospital were selected. Model performance was measured by c-index and calibration curve. The results were further validated using bootstrap and a cohort of 38 patients from a branch hospital who underwent surgery from 2006 to 2014.ResultsBackward stepwise selection and Lasso were applied respectively to select predictors. T stage, N stage, and preoperative serum fibrinogen were included in the final model. Predictions correlated well with observed 1- and 3-year survival. The c-index for predicting survival was 0.74 (95% confidence interval, 0.70–0.78), which was statistically higher than that of the AJCC 7th system and Nevin system (P=0.04, 0.04, respectively). In the validation cohort, the nomogram performed better than the other two staging systems (c-index: 0.71 vs. 0.67 and 0.67).ConclusionsThe validated nomogram is a practical tool for predicting the overall survival (OS) of postoperative GBC patients. Preoperative serum fibrinogen levels were associated with tumor progression and may be an independent predictor for GBC patients.     

TACE联合索拉非尼治疗中晚期肝细胞性肝癌的临床研究

目的探讨经导管动脉化疗栓塞（transcatheterarterialchemoembolization,TACE）联合索拉非尼治疗中晚期肝细胞性肝癌（hepatocellularcarcinoma,HCC）的疗效及安全性。方法选择我院70例中晚期HCC患者,其中35例给予TACE联合索拉非尼治疗（观察组）,35例单纯行TACE治疗（对照组）。每4-8周根据实体瘤疗效评估标准（RECIST）行肿瘤应答评价,评估临床疗效及索拉非尼毒副反应,比较两组患者治疗后的中位生存期及中位疾病进展时间。结果观察组和对照组中位0s分别为14_8个月和8．2个月,差异有统计学意义（P〈0．05）,中位TIP分别为10．3个月和5．8个月,差异有统计学意义（P〈0．05）。观察组服用索拉非尼后有27例（77．1％）患者出现毒副反应,经对症治疗后好转。结论TACE联合索拉非尼治疗中晚期HCC疗效好,不良反应可耐受,有望成为中晚期HCC的一种治疗模式。     

Development of a novel combined nomogram model integrating Rad-score,age and ECOG to predict the survival of patients with hepatocellular carcinoma treated by transcatheter arterial chemoembolization

BackgroundLiver cancer is affecting more and more people''s health. Transcatheter arterial chemoembolization (TACE) has become a routine treatment option, but the prognosis of patients is not optimistic. Effectively prediction of prognosis can provide clinicians with an objective basis for patient prognosis and timely adjustment of treatment strategies, thus improving the quality of patient survival. However, the current prediction methods have some limitations. Therefore, this study aims to develop a radiomics nomogram for predicting survival after TACE in patients with advanced hepatocellular carcinoma (HCC).MethodsSeventy advanced HCC patients treated with TACE were enrolled from January 2013 to July 2019. Clinical information included age, sex, and Eastern Cooperative Oncology Group (ECOG) score. Overall survival (OS) was confirmed by postoperative follow-up. Radiomics features were extracted using 3D Slicer (version 4.11.20210226) software, then obtain radiomics signature and calculate radiomics score (Rad-score) for each patient. Univariate and multivariate Cox regression were used to analyze the baseline clinical data of patients and establish clinical models. The obtained radiomics signature was incorporated into the clinical model to establish the radiomics nomogram. The predictive performance and calibration ability of the model were assessed by the area under the receiver operating characteristic (ROC) curve (AUC), C-index, and calibration curve.ResultsThree significant features were selected from 851 radiomics features by the least absolute shrinkage and selection operator (LASSO) Cox regression model to construct the radiomics signature, and were significantly correlated with overall survival (P<0.001). Rad-score, age, and ECOG score were combined to construct a radiomics nomogram. The AUC, sensitivity, and specificity of the radiomics nomogram were 0.801 (95% CI: 0.693–0.909), 0.822 (95% CI: 0.674–0.915), and 0.720 (95% CI: 0.674–0.915), respectively. The C-index of the radiomics nomogram was 0.700 (95% CI: 0.547–0.853). Calibration curves showed better agreement between the predicted and actual probabilities in the radiomics nomogram among the 3 features.ConclusionsThe Rad-score was a strong risk predictor of survival after TACE for HCC patients. The radiomics nomogram might be improved the predictive efficacy of survival after TACE and it may also provide assistance to physicians in making treatment decisions.     

沙利度胺联合肝动脉栓塞化疗治疗原发性肝癌随机对照研究

背景与目的:肝动脉栓塞化疗(transcatheter arterial chemoembolization,TACE)是治疗中晚期肝癌的重要手段.但是如何巩固TACE的效果,进一步提高中晚期肝癌的长期生存,是亟待研究与解决的重要问题.本研究旨在评价沙利度胺联合TACE治疗原发性肝癌的临床疗效,探索以介入治疗为主的中晚期肝癌的综合治疗模式.方法:以疾病进展时间、生存期为观察终点指标,采用前瞻性随机对照研究,对2004年8月至2006年8月入组的96例原发性肝癌患者随机分为治疗组和对照组,治疗组给予沙利度胺200 mg/d口服1～6个月联合TACE,对照组单纯行TACE.TACE用药选用吉西他滨0.4～1.6 g、奥沙利铂100～200 mg、氟尿嘧啶脱氧核苷0.5～1.0 g,栓塞剂选用碘化油、明胶海绵、无水乙醇.观察沙利度胺的不良反应,同时观察患者的生存期并作预后因素分析.结果:治疗组与对照组患者的中位生存期分别为18个月(95%可信区间12～24个月)、13个月(95%可信区间11～15个月),治疗组半年、1年、2年生存率为85.6%、66.2%、29.9%,对照组半年、1年、2年生存率为85.6%、57.2%、29.1%.治疗组与对照组中位疾病进展时间分别为181天(95%可信区间91～271天)和97天(95%可信区间33～161天),差异有统计学意义(P＜0.05).剔除口服沙利度胺不足1个月的病例后,治疗组与对照组中位生存期分别为28个月(95%可信区间11～45个月)和13个月(95%可信区间8～18个月);治疗组半年、1年、2年生存率为97.0%、75.3%、51.0%,对照组分别为84.8%、54.9%、24.6%.Kaplan-Meier生存曲线和log-rank检验结果表明,两组生存期相比差异有统计学意义(P＜0.05).治疗组5例(11.1%)发生严重皮疹,3例(6.7%)严重嗜睡.Cox回归分析表明,TACE次数是影响肝癌预后的独立因素.结论:口服沙利度胺联合TACE较单纯栓塞化疗能明显延长患者疾病进展时间与生存期,TACE次数与预后相关.     

APRI评分对HBV相关肝细胞癌切除术患者预后的预测价值

目的:评估天冬氨酸转氨酶与血小板计数比值指数（APRI）对HBV相关肝细胞癌（HCC）切除术患者术后总生存率（OS）的预测价值。方法:采用回顾性队列研究方法,收集2012年1月至2016年12月期间在广西医科大学附属肿瘤医院行切除术治疗的1 031例HBV相关HCC患者的术前临床资料。通过Kaplan-Meier生存曲线确定APRI评分的cutoff值。采用Kaplan-Meier法绘制不同APRI组患者的生存曲线,并通过Log-rank检验评估两组人群的生存差异。运用逐步多因素Cox回归筛选患者OS独立影响因素。采用限制性立方条图（RCS)评价患者APRI与死亡风险的相关性。建立列线图模型评估APRI对OS的预测能力并内部验证。结果:RCS显示APRI与死亡风险呈非线性关联（非线性P＜0.001）。多因素Cox回归结果显示:APRI、BCLC分期、AFP、性别和肿瘤大小是OS独立影响因素,高APRI组死亡风险是低APRI组2.1倍。患者OS的列线图显示APRI对OS的预测能力仅次于BCLC分期。在建模组和验证组中预测OS列线图的C-index分别为0.71（95%CI:0.68~0.74）、0.69（95%CI:0.64~0.75）;1和5年OS校正曲线显示列线图具有良好的校准度;临床决策曲线（DCA）显示模型具有良好的临床应用价值。结论:APRI是HBV相关HCC切除术患者OS独立影响因素,基于APRI对患者预后进行分层,有利于进行个体化治疗和随访。     

海藻酸钠微球在肝动脉化疗栓塞治疗中晚期原发性肝癌中的疗效研究

目的 比较海藻酸钠(KMG)微球和明胶海绵颗粒在肝动脉化疗栓塞中的栓塞效能、疗效,并探讨栓塞效能和疗效间的关系.方法 接受KMG微球及明胶海绵颗粒栓塞的同质中晚期肝癌患者各50例,分别为实验组和对照组,比较两组患者的栓塞效能(术后1个月瘤灶的碘油沉积率)以及栓塞疗效,并比较栓塞效能与疗效间的关系.结果 术后第一个月的碘油沉积率实验组和对照组分别为(81.32±13.322)%和(50.78±19.723)%;差别有统计学意义.2年肝内肿瘤进展率实验组和对照组分别为48%和68%;差异有统计学意义;无进展生存率实验组和对照组分别为46%和26%,有统计学意义.实验组和对照组1年和2年生存率分别82%,72%和60%,38%;差异有统计学意义.实验组和对照组1、2年肝外肿瘤进展率分别2%,4%和20%,30%,有统计学意义.1年肝内肿瘤进展及1年无进展生存率,两组比较无差别.实验组和对照组1年生存率分别为82.2%和33.3%;差异有统计学意义,而无进展生存率分别为74.0%和30.4%;P=0.009,且1年肝内肿瘤进展率分比为4.1%和29.6%;P<0.001,肝外肿瘤进展率实验组和对照组分别为0.31%vs 35.5%;P<0.001.结论 KMG微球治疗应用于肝动脉化疗栓塞术中治疗原发性肝癌安全,患者耐受良好;作为栓塞剂,较之明胶海绵颗粒,能取得更优的近期以及远期疗效. 肿瘤灶中碘油的沉积率作为栓塞效果的指标,碘油沉积率较高的肝癌患者其预后往往更优于乏碘油沉积的肝癌患者.     

Advanced hepatocellular carcinoma treated by transcatheter arterial chemoembolization with drug-eluting beads plus lenvatinib versus sorafenib,a propensity score matching retrospective study

Recently, a prospective randomized study suggested that transcatheter arterial chemoembolization (TACE) plus lenvatinib, as opposed to TACE plus sorafenib, was an effective and promising treatment for patients with advanced hepatocellular carcinoma (HCC) having portal vein thrombus (PVTT) and large tumor burden. However, no propensity score matching retrospective studies on TACE with drug-eluting beads (DEB-TACE) plus lenvatinib (DEB-TACE+LEN) versus DEB-TACE plus sorafenib (DEB-TACE+SOR) for advanced HCC has been reported to date. The medical records of consecutive patients with advanced HCC who underwent DEB-TACE+LEN or DEB-TACE+SOR between January 2017 and December 2020 were retrospectively reviewed. Mutation genes (VEGF, ANG2, FGF19, FGF21, and FGF23) were measured by whole-exome sequencing (WES). Adverse events (AEs), objective response rate (ORR), disease control rate (DCR), overall survival (OS) and time to progression (TTP) were compared between patients who underwent DEB-TACE+LEN and DEB-TACE+SOR. In total, 150 patients were enrolled in this study. The DEB-TACE+LEN group (n=50) showed significantly better ORR (64.0% vs. 33.3%; P=0.008), OS (hazard ratio [HR]=0.63, 95% confidence interval (CI): 0.41-0.98; P=0.043), and TTP (HR=0.65, 95% CI: 0.45-0.94; P=0.023) than that in the DEB-TACE+SOR group (n=100). Subgroup analyses showed that in patients with portal vein tumor thrombus (PVTT), OS and TTP were significantly longer in the DEB-TACE+LEN group than in the DEB-TACE+SOR group (HR=0.59, 95% CI: 0.36-0.98; P=0.043; HR=0.89, 95% CI: 0.35-2.29; P=0.035). In patients with FGF21 amplification, OS was also significantly longer in the DEB-TACE+LEN group than that in the DEB-TACE+SOR group (HR=0.19, 95% CI: 0.06-0.66; P=0.003). The patients in DEB-TACE+LEN group had a significantly lower incidence of hand-foot skin reaction (32.0% vs. 49.0%; P=0.048), but a higher incidence of proteinuria (26.0% vs. 10.0%; P=0.010) than that in the DEB-TACE+SOR group. In conclusion, DEB-TACE+LEN conferred better ORR, OS and TTP than did DEB-TACE+SOR in patients with advanced HCC, especially those with PVTT and FGF21 amplification, with acceptable AEs; thus making it a superior treatment modality for these patients.     

Low serum levels of vitamin D in metastatic cancer patients: a case–control study

We aimed to elucidate whether serum VEGFR2 concentration before and after transarterial chemoembolization (TACE) can predict survival in patients with unresectable hepatocellular carcinoma (HCC). Serum VEGFR2 concentrations were serially measured in 169 patients with advanced HCC before and after TACE. We defined a decrease in the serum VEGFR2 level >10 % from the pretreatment level as response. Serum VEGFR2 concentrations decreased in 44 (26.0 %) patients at week 4. Patients who had a VEGFR2 response at week 4 had a longer median survival than those who did not have a VEGFR2 decrease (19.0 vs. 9.8 months, p < 0.001). Clinical variables associated with OS in addition to VEGFR2 response also included extrahepatic metastases (p = 0.005) and vascular invasion (p = 0.035). VEGFR2 decrease after TACE (p = 0.012) and presence of extrahepatic metastases (p = 0.02) were independently associated with OS by multivariate analysis. A serum VEGFR2 concentration decrease at 4 weeks after TACE may predict favorable overall survival in patients with advanced HCC.     

Preoperative transcatheter arterial chemoembolization reduces long-term survival rate after hepatic resection for resectable hepatocellular carcinoma.

AIMS: To study the effect of preoperative transcatheter arterial chemoembolization (TACE) on long-term survival after hepatic resection for hepatocellular carcinoma (HCC), we conducted a comparative analysis in 235 HCC patients who underwent hepatic resection with a curative intent. METHODS: We compared clinicopathologic background, mortality, and survival rates after hepatic resection between those who underwent preoperative TACE (n=109) and those who did not (n=126). RESULTS: One hundred and two patients in the TACE group (93.6%) received TACE only once. The mean interval between TACE and hepatic resection was 33.1days. Patients in the TACE group were younger than those in the non-TACE group, and liver cirrhosis and non-anatomical hepatic resection were more prevalent in this group. The 5-year overall survival rate after hepatic resection was significantly lower in the TACE group (28.6%) than in the non-TACE group (50.6%), especially in patients without cirrhosis or with stage I or II tumor. There was no difference between the two groups in mortality or disease-free survival after hepatic resection. Multivariate analysis showed preoperative TACE, preoperative aspartate aminotransferase elevation, and microscopic portal invasion to be independent risk factors for a poor outcome after hepatic resection. CONCLUSIONS: Preoperative TACE should be avoided for patients with resectable HCC, especially for those without cirrhosis or with an early stage tumor.