Local radiotherapy for unresectable hepatocellular carcinoma patients who failed with transcatheter arterial chemoembolization

Purpose: The purpose of this study was to investigate the efficacy of local radiotherapy (RT) as a salvage treatment for unresectable hepatocellular carcinoma (HCC) patients who failed with transcatheter arterial chemoembolization (TACE).

Methods and Materials: Patients with unresectable HCC who had been treated with and eventually failed with TACE were eligible. The judgment of TACE failure was based on incomplete tumor filling of lipiodol-adriamycin mixture on either angiography or computed tomography (CT) scan. From January 1993 to December 1997, 27 patients were entered into this study. They had UICC Stage III (17) or IVA (10) disease, with a mean tumor size of 7.2 ± 2.9 cm. Local RT was done, with a mean tumor dose of 51.8 ± 7.9 Gy, in daily 1.8-Gy fractions using a 10- or 6-MV linear accelerator. Survival was calculated from both the diagnosis and the start of RT using the Kaplan-Meier method.

Results: An objective response was observed in 16 of 24 patients (66.7%) including 1 CR. Intrahepatic metastasis was noted outside the RT field in 10 patients (37.0%). Extrahepatic distant metastasis occurred in 4 patients. Survival rates at 1, 2, and 3 years were 85.2%, 58.1%, and 33.2%, respectively, from the diagnosis and 55.9%, 35.7%, and 21.4%, respectively, from the start of RT. The median survivals were 26 months from the diagnosis and 14 months from the start of RT. Acute toxicity involved alteration in liver function test (13 patients) and thrombocytopenia (2 patients). Subacute and chronic toxicity involved gastroduodenal ulcer (3 patients) and duodenitis (2 patients). There was no treatment-related death.

Conclusion: In unresectable HCC patients who failed with TACE, local RT induced a substantial tumor response of 66.7%, with a 3-year survival rate of 21.4% and a median survival time of 14 months. Toxicity was significant but manageable. Although we do not know if there is survival benefit through this treatment, local RT in these patients seems to be valuable as a salvage for TACE-failed HCC.     

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.     

Liver fibrosis and five year survival of hepatocellular cancer cases undergoing transcatheter arterial chemo embolization using small doses

Objective: To investigate liver fibrosis, TGF-β1 levels and curative effects on hepatocellular carcinoma (HCC)with small and conventional dose perfusion chemotherapy by transcatheter arterial chemo embolization (TACE).Methods: Thirty-six hepatocellular carcinoma patients not indicated for surgical resection underwent superselectivetranscatheter arterial chemoembolization, divided into small dose (n=15) and conventional dose (n=21)chemotherapy groups. Results: With conventional doses, four indices of liver fibrosis focusing on hyaluronateacide (HA), human procollagen type-Ⅲ (hPC-Ⅲ), collagen type-Ⅳ (Ⅳ-C) and transforming growth factor-βl(TGF-β1) were obviously increased postoperative compared with preoperative (P<0.01); in contrast, with smalldoses there were no significant differences except for TGF-β1. Five year survival demonstrated no significantdifferences between the two groups (P>0.05). Conclusion: To hepatocellular carcinoma patients treated byTACE, reducing doses of chemotherapy drugs can reduce progress of liver fibrosis, without impacting on fiveyear survival.     

原发性肝癌病人肝动脉化疗栓塞术治疗的护理

目的探讨肝癌病人肝动脉化疗栓塞术治疗的护理方法。方法观察42例原发性肝癌病人肝动脉化疗栓塞术治疗前后病情的变化，并在治疗前后给予相应的护理。结果经过治疗和精心护理，本组病人治疗顺利，无严重不良反应和并发症，病人病情得到明显改善。结论有效的术前及术后护理可以消除病人紧张心理，预防和减少并发症，提高治疗的效果。     

Radiotherapy combined with transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma - a prospective clinical trial

Objective： This study evaluated the therapeutic effect of external beam radiotherapy （RT） combined with transcatheter arterial chemoembolization （TACE） on the patients with unresectable hepatocellular carcinoma （HCC）. Methods： From June 1994 to April 2002, 114 patients with unresectable HCC were nonrandomized prospectively stepped into our study. All patients received TACE as initial therapy, except 54 also received combination therapy with external beam therapy. Survival failure patterns were analyzed and compared between the two groups. Results： Overall survival rates in the patients in the radiotherapy group were 65%, 47%, 38% at 1,2, 3 years, respectively, improved over the non-radiotherapy group rates of 54%, 36.5%, 18% at 1, 2, 3 years, respectively. There was significant difference between two groups （P 〈 0.05）. The survival rates correlated with tumor size, number of tumors, and portal vein embolus. Conclusion： TACE combined with RT is a more effective treatment than TACE alone in patients with unresectable HCC.     

立体适形放射治疗联合肝动脉化疗栓塞治疗肝细胞性肝癌的临床研究

目的 观察立体适形放射治疗（3DCRT）联合肝动脉化疗栓塞（TACE）治疗肝细胞性肝癌（HCC）的疗效和患者的耐受性。方法 46例HCC患者,先采用TACE治疗1-3次,再进行3DCRT.2Gy／次,每天1次,每周5d。肿瘤剂量30-54 Gy,总疗程3-6周。放疗结束后采用世界卫生组织（WHO）标准评价疗效,采用美国国立癌症研究所（NCI）的毒性标准和美国放射治疗肿瘤组（RTOG）的毒副反应评价标准评价急慢性肝脏毒副反应及其他毒副反应。结果 46例患者中,部分缓解（PR）8例,稳定（SD）35例,进展（PD）3例。全组患者中位生存时间16个月,1、2、3年生存率分别为60．9％、39．1％和28．3％。1、2、3年局部控制率分别为73．9％、56．5％和39．1％。1、2、3年远处转移率分别为15．2％、21．7％和34．8％。单因素分析表明,T分期、广州会议分期、门脉癌栓（PVT）、放疗前肝硬化Child-Pugh分级和肿瘤照射剂量对生存率的影响有统计学意义。Cox多因素分析显示,肿瘤照射剂量和肝硬化Child-Pugh分级是HCC患者预后的独立影响因素。5例患者发生急性肝脏毒副反应,1级2例,3级3例。3例出现1级上消化道急性损伤,其中1例出现轻度上消化道出血。10例出现1或2级外周血白细胞降低。2例出现放射性肝病。结论 3DCRT联合TACE综合治疗HCC安全、有效,值得进一步研究。     

肝动脉插管化疗栓塞在预防肝癌术后复发中的应用价值

目的评价肝动脉插管化疗栓塞（TACE）治疗对预防肝癌术后复发的应用价值。方法本研究设TACE治疗组和对照组（非TACE治疗组）。治疗组987例,均为在我院行肝癌切除术及第1次预防性TACE治疗后无明显复发,但其后在不同时间内出现复发的患者;对照组643例,为在我院行肝癌切除术后未进行TACE治疗的患者。分析TACE治疗组和对照组病例的复发时间及其与TACE治疗和非TACE治疗间的关系。结果治疗组和对照组的复发率在6个月内分别为22．2％（219例）和61．6％（396例）,两组差异有统计学意义（u=14．83,P〈0．01）,对照组复发率显著高于治疗组;12个月内分别为78．0％（770例）和74．7％7％（480例）,两组差异无统计学意义（u=1．43,P〉0．05）;18个月分别为88．6％（874例）和80．1％（515例）,两组差异有统计学意义（u=4．38,P〈0．01）,治疗组复发率高于对照组。结论术后TACE的主要作用在于抑制和及早发现微转移灶和治疗未能切除干净的微小残癌病灶,在6个月内预防效果较好;在不能确定肝癌是否为单中心还是多中心发生时,以及在不能确定术后是否存在残癌灶和微小转移灶时,术后TACE仍是有价值的。     

Hepatitis B virus reactivation in hepatocellular carcinoma patients undergoing transcatheter arterial chemoembolization therapy

Aim: The effect of transcatheter arterial chemoembolization (TACE) therapy on hepatitis B virus (HBV) reactivation in hepatocellular carcinoma (HCC) patients with prior resolved hepatitis B is not fully understood. Methods: From January 2006 to December 2010, 43 hepatitis B surface antigen (HBsAg)‐negative/anti‐hepatitis B core antigen (HBc) positive patients with newly diagnosed unresectable HCC were enrolled in the study. All underwent TACE therapy. Results: Four patients (9.3%) developed HBV reactivation with mild/moderate hepatitis. The median number of TACE cycles received was 3.5 (range 3–4 cycles). The median time interval between the occurrence of HBV reactivation and the completion of TACE therapy was 3 months (range 1–5 months) and their median HBV DNA level was 1.58 × 10⁴ IU/mL (range, 1.65 × 10³–6.42 × 10⁴ IU/mL). After the introduction of lamivudine at the occurrence of HBV reactivation, all had resolution of hepatitis. An exploratory analysis indicated that significant predictors of HBV reactivation included increased serum total bilirubin coexisting with cirrhosis and the total number of cycles of TACE received. Conclusion: The administration of TACE therapy may increase the risk of HBV reactivation in HBsAg‐negative/anti‐HBc‐positive patients diagnosed with unresectable HCC. Further studies are warranted to explore the optimal management of HBV reactivation in patients with prior resolved hepatitis B.     

肝动脉化疗栓塞术后胸腺法新联合索拉菲尼治疗中晚期肝癌的疗效分析

目的:探讨中晚期肝细胞型肝癌患者肝动脉化疗栓塞术(transcatheter arterial chemoembolization,TACE)后索拉菲尼联合胸腺法新的疗效分析.方法:回顾性研究第四军医大学附属唐都医院54例中晚期原发性肝癌患者,所有患者均为乙型肝炎表面抗原阳性,并均接受了TACE手术治疗.在手术治疗后三天,开始口服索拉菲尼,以及皮下注射胸腺法新,观察患者的肝功能,计算治疗的有效率以及患者的生存时间.结果:观察组患者的总体有效率82.8%,显著高于对照组的56%,差异有统计学意义(P=0.032);观察组平均生存时间为13.8个月,对照组为10.2个月,可认为观察组生存时间长于对照组(P=0.021);治疗前两组AST、ALT以及白蛋白无明显差异(P>0.05);治疗3个月后与治疗前相比,两组的AST和ALT均得到改善(P<0.05),并且观察组白蛋白提高(P<0.001).结论:胸腺法新、索拉菲尼联合TACE的治疗方法可以有效的改善肝炎病毒所致的原发性肝癌的预后,提高患者的生存期,值得临床推广.     

肝癌术后肝动脉化疗栓塞治疗患者肿瘤复发的影响因素分析

目的 探讨影响肝癌术后经导管肝动脉化疗栓塞治疗(TACE)患者肿瘤复发的危险因素.方法 选择并收集200例肝癌患者的年龄、性别等一般人口学特征和临床特征资料并对患者进行随访追踪,采用Logistic逐步回归分析法分析肿瘤复发的影响因素.结果 在200例患者中130例有肿瘤复发,占65.0％.Logistic逐步回归分析结果显示,血管癌栓(OR=3.796;95％CI:1.871～7.702)、侵透肝被膜(OR=3.340;95％CI:1.067～10.451)、肝硬化(OR=2.790;95％CI:1.771～4.396)、包膜完整性(OR=2.048;95％CI:1.273～3.298)和最大癌结节直径(OR=1.739;95％CI:1.014～2.980)是肝癌术后TACE治疗患者肿瘤复发的危险因素.结论 肝癌术后TACE治疗患者的肿瘤复发率较高,术前有无血管癌栓、侵透肝被膜和肝硬化,包膜是否完整,以及肿瘤的直径等均会影响肿瘤复发,临床需要加强患者术后复诊和康复治疗.     

Efficacy and safety of high-intensity focused ultrasound ablation for hepatocellular carcinoma by changing the acoustic environment: microbubble contrast agent (SonoVue) and transcatheter arterial chemoembolization

Objective: To compare efficacy and safety of microbubble contrast agent (SonoVue) and transcatheter arterial chemoembolization (TACE) in combination with high-intensity focused ultrasound (HIFU) for treatment of patients with hepatocellular carcinoma (HCC).

Methods: According to our inclusion criteria, we retrospectively reviewed 52 patients with HCCs, and divided them into SonoVue group and TACE group. Tumors were examined by enhanced magnetic resonance imaging. Change of lesions, alpha-fetoprotein values, hepatic and renal function were measured pre- and postoperatively. Then, adverse events were observed and clinical follow-up was performed.

Results: Clinical efficacy and the majority of treatment parameters were similar, except for time and energy required for the first massive grey-scale changes in SonoVue group, which were significantly lower than those in TACE group (p?<?.05). For adverse events, only rate of fever (3.85%) in SonoVue group was significantly lower than that in TACE group (50.00%, p?<?.05). The ‘diagnosis and treatment cycle’ in SonoVue group (11.5?±?2.9) was remarkably shorter than TACE group (22.7?±?6.3, p?<?.05). Energy efficiency factor was positively correlated with distance from the deepest layer of lesion to the hepatic capsule or to the abdominal wall in SonoVue group, while that was negatively correlated with iodized oil deposition in TACE group.

Conclusion: Using microbubble (SonoVue) in HIFU procedure has a similar therapeutic effect compared with TACE, and does not increase the risk of treatment. It might present a new strategy in clinical treatment, especially for patients with a smaller diameter of HCC.     

艾迪注射液联合肝动脉灌注栓塞治疗原发性肝癌108例临床观察

目的:评价中药艾迪注射液联合肝动脉灌注栓塞治疗法治疗肝癌的疗效。方法:108例原发性肝癌患者随机分为治疗组和对照组,每组各54例。治疗组采用艾迪注射液60ml+0.9%氯化钠溶液500ml静脉点滴,d1-d21;静滴同时进行肝动脉灌注栓塞治疗,药物为羟基喜树碱(HCPT)10mg,氟尿嘧啶(5-FU)500mg,碘化油10ml,按Seldinger’s技术要求,将药物注入肝脏肿瘤供养血管并行栓塞,28d为1周期。对照组54例单用肝动脉灌注栓塞治疗方案,同治疗组,2个周期后评价。结果:治疗组和对照组的有效率分别为80.4%和63.4%,中位生存期分别为8.34个月和8.21个月,6个月生存率分别为89.1%和84.8%,12个月生存率分别为63.4%和47.8%,24个月生存率分别为28.3%和17.4%。全组初治者6个月生存率83.1%,12个月生存率46.2%,24个月生存率18.5%,复治者则分别为96.2%,77.8%,33.3%。AFP疗后下降者治疗组29例有效率为69.4%,对照组21例,有效率为54.5%。结论:艾迪注射液能提高肝动脉灌注栓塞治疗疗效,改善生存质量,延长生存期。     

BRCA1基因miRNA结合位点多态性与肝细胞癌术后总生存期的关联研究

目的 探讨BRCA1基因microRNA(miRNA)结合位点上的单核苷酸多态性对肝细胞癌(hepatocellular carcinoma,HCC)患者术后总生存期(overall survival,OS)的影响.方法 纳入2004年6月—2013年12月于广西医科大学附属肿瘤医院接受根治术切除的363例HCC患者为...     

4种评分系统预测肝细胞癌患者经肝动脉化疗栓塞术后肝衰竭的价值

目的:探讨Child-Pugh(CTP)、ALBI、MELD、MELD-Na评分预测肝细胞癌(hepatocellular carcinoma,HCC)经肝动脉化疗栓塞(transcatheter arterial chemoembolization,TACE)治疗后并发慢性加急性肝衰竭(acute-on-chronic liver failture,ACLF)的价值。方法:回顾性分析2013月10月至2015年10月广西医科大学附属肿瘤医院接受首次TACE治疗的711例HCC患者的临床资料,采用Logistic回归分析及受试者工作特征(receiver operating characteristic,ROC)曲线评估4种评分模型预测ACLF的价值。结果:单因素、多因素分析结果均提示4种评分模型能独立预测TACE术后ACLF的发生(均P<0.05);ROC曲线分析显示,ALBI的受试者工作特征曲线下面积(area under curve,AUC)均显著高于其余三种评分的AUC(均P<0.001)。不同分型ACLF按4种评分模型的最佳截断(cut-off)值分组后,Chil...     

DC‐SIGN and VDR polymorphisms are associated with chronic form of paracoccidioidomycosis with oral manifestations

Paracoccidioidomycosis (PCM) is a granulomatous disease caused by fungi of the species complex of the Paracoccidioides genus. One of the main clinical manifestations of PCM is the presence of oral lesions with the presence of epithelioid granulomas. In this work, we aimed to evaluate the frequency of SNPs in the TNF‐α, JAK1, VDR, DC‐SIGN and FcγRIIa genes in patients with chronic PCM and verify possible association of these SNPs with the organisation pattern of the granulomas in the oral lesions. A total of 66 samples of DNA were obtained from oral lesions biopsies and 106 DNA samples were obtained from healthy individuals. The individuals were genotyped for SNPs in DC‐SIGN (rs4804803), FcγRIIa (rs1801274), JAK1 (rs11208534), TNF‐α (rs1800629) and VDR (rs7975232) by real‐time PCR and allele discrimination method. Granulomas were classified as loose or dense according to the histological pattern. In the VDR (rs7975232), the CC genotype (P < 0.001, OR = 5.94, 95% CI = 2.07‐17.05), and the C allele (P = 0.027, OR = 2.71, 95% CI = 1.07‐6.86), as well as the GG genotype in DC‐SIGN (rs4804803) (P = 0.032, OR: 3.76, 95%, I = 1.06‐13.38) are associated with an increased risk of oral PCM. Our data indicate that VDR and DC‐SIGN genetics variations are related to the susceptibility of oral PCM in the group of patients analysed.     

Study on efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with regorafenib and PD-1 antibody versus continued TACE combined with regorafenib in patients with hepatocellular carcinoma after failed second-line treatment with regorafenib

BackgroundAt present, there is no standard for the posterior treatment of hepatocellular carcinoma (HCC). This study isTo evaluate and compare the safety and efficacy of transcatheter arterial chemoembolization (TACE) combined with regorafenib and anti-PD-1 antibody with continued TACE combined with regorafenib in patients with HCC after the failure of second-line treatment with regorafenib.MethodsWe enrolled patients with advanced HCC who were treated with sorafenib and sequential regorafenib. All patients were treated with TACE and found to have tumor progression in 2021. After tumor progression, patients were treated with TACE combined with regorafenib and PD-1 antibody or with continued TACE combined with regorafenib according to the wishes of the patient. Efficacy was evaluated after 1 month of treatment. The objective response rate (ORR), disease-control rate (DCR), and safety were evaluated according to adverse reactions of patients.ResultsNine patients were treated with TACE combined with regorafenib and PD-1 antibody, and the 9 patients continued to receive TACE combined with regorafenib. There was no significant difference in baseline data between the 2 groups. In the PD-1 group five patients achieved a partial response (PR), three achieved stable disease (SD), and one patient had progressive disease (PD) after 1 month of treatment. The ORR was 55.6% and the DCR was 88.9%. In the continued TACE–regorafenib group, four patients achieved PR, one achieved SD, and four patients achieved PD after 1 month of treatment, while the ORR was 44.4% and the DCR was 55.6%. There was a significant difference in the DCR between the two groups (P=0.012), while adverse events were similar in both.ConclusionsTACE combined with regorafenib and PD-1 antibody had a higher DCR and was more effective than continued TACE combined with regorafenib in patients with HCC who failed second-line treatment with regorafenib. However, PD-1 antibody therapy might increase the risk of death by causing an uncontrollable immune response. Given the risk of an immune response, patients may choose to continue TACE combined with regorafenib, given the similar ORR of the two treatments.     

脾动脉部分栓塞联合肝动脉化疗栓塞治疗原发性肝细胞癌合并脾亢的临床研究

背景与目的：原发性肝细胞癌（primary hepatocellular carcinoma,PHC）患者70％-90%有肝硬化、脾功能亢进以致患者术前外周血象偏低或术后外周血象恢复缓慢常影响经肝动脉化疗栓塞（transcatheter hepatic arterial chemoembolization,TACE）的正常进行。本研究探讨脾动脉部分栓塞（partial splenic embolization,PSE）联合经TACE治疗合并脾功能亢进的PHC的方法和意义。方法：对26例PHC患者采用PSE联合TACE治疗的方法,26例PHC患者单用TACE治疗。结果：PSE联合TACE较单用TACE治疗明显改善PHC患者外周血象,PSE术后3天、1周、2周及4周外周血白细胞、红细胞、血小板较栓塞前明显提高。结论：PSE联合TACE是PHC合并脾亢的安全、有效治疗方法。     

TACE联合3DCRT治疗肝癌伴门静脉癌栓疗效分析

目的：分析肝动脉化疗栓塞（TACE）结合三维适形放射治疗对原发性肝癌（HCC）并门静脉癌栓（PVVT）的疗效。方法：2004年10月至2009年10月,共收治32例HCC合并PVVT患者,采用肝动脉化疗栓塞联合三维适形放射治疗,观察肿瘤及癌栓的近期疗效,用Kaplan-Meier法进行生存分析,采用Cox比例风险模型作多因素分析。结果：原发灶肿瘤近期有效率71.9%,癌栓有效率为81.3%。平均生存时间为20.63±1.23个月,中位生存时间为19.0±1.02个月。多因素分析显示肿瘤分期、癌栓类型、肝功Child-Pugh分级、卡氏评分是影响预后的主要因素（P〈0.05）。结论：TACE联合3DCRT治疗肝癌合并PVTT疗效好,损伤小,易耐受,是治疗HCC合并PVTT有效治疗方法。     

TACE联合3DCRT治疗肝癌伴门静脉癌栓疗效分析

目的:分析肝动脉化疗栓塞(TACE)结合三维适形放射治疗对原发性肝癌(HCC)并门静脉癌栓(PVVT)的疗效。方法:2004年10月至2009年10月,共收治32例HCC合并PVVT患者,采用肝动脉化疗栓塞联合三维适形放射治疗,观察肿瘤及癌栓的近期疗效,用Kaplan-Meier法进行生存分析,采用Cox比例风险模型作多因素分析。结果:原发灶肿瘤近期有效率71.9%,癌栓有效率为81.3%。平均生存时间为20.63±1.23个月,中位生存时间为19.0±1.02个月。多因素分析显示肿瘤分期、癌栓类型、肝功Child-Pugh分级、卡氏评分是影响预后的主要因素(P<0.05)。结论:TACE联合3DCRT治疗肝癌合并PVTT疗效好,损伤小,易耐受,是治疗HCC合并PVTT有效治疗方法。