肝动脉化疗栓塞联合索拉非尼治疗肝细胞癌合并肺转移的临床观察

目的 评价肝动脉化疗栓塞(TACE)联合索拉非尼治疗肝细胞癌(HCC)合并肺转移的疗效和安伞性.方法 30例伴有肺转移的晚期HCC患者,于TACE治疗后3周复查,如无禁忌证即开始服用索拉非尼,400 mg/次,2次/d;不能耐受时减至200 mg/次,2次/d.每4周进行疗效评估.结果 肺部转移病灶缩小6例,病灶稳定8例;肝脏病灶稳定22例,进展8例,在服药期问行TACE1～3次.不良反应包括手足皮肤反应7例,疲乏无力18例,脱发6例,腹泻6例,贫血和骨髓抑制5例,高血压2例,消化道出血1例.结论 HCC合并肺转移时,TACE联合索拉非尼治疗可有效控制疾病进展,安伞性及患者耐受性良好.     

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。     

经导管肝动脉化疗栓塞联合索拉非尼治疗中晚期肝细胞癌的临床观察

目的 观察经导管肝动脉化疗栓塞(TACE)联合索拉非尼治疗中晚期肝细胞癌的有效性和安全性.方法 40例已接受过TACE治疗的中晚期肝细胞癌患者口服索拉非尼单药治疗,400mg,2次/d,直至病情进展或出现不可耐受的毒性反应.按照实体瘤疗效评价标准(RECIST)评价疗效,按照美国国立癌症研究所常见毒性事件标准(NCI-CTCAE)评价不良反应.结果 40例中晚期肝细胞癌患者中,获得完全缓解1例,部分缓解7例,疾病稳定19例,疾病进展13例,疾病控制率为67.5%.全组患者的生存时间为1～18个月,1年生存率为54.0%.主要不良反应为手足皮肤反应,其次是腹泻和血小板计数降低.结论 TACE联合索拉非尼治疗中晚期肝细胞癌是有效和安全的.     

索拉非尼治疗不能手术的原发性肝细胞癌的疗效及预后因素

目的 研究索拉非尼治疗不能手术的原发性肝细胞癌(HCC)的疗效以及预后影响因素.方法 2005年12月至2009年3月间,50例肝功能分级为Child-Pugh A级的不能手术的原发性HCC患者连续口服索拉非尼治疗,索拉非尼用法为400 mg/次,每日2次.每6～8周复查CT或MRI,根据实体瘤疗效评价标准(RECIST)进行疗效评价,根据美国国立癌症研究所常见毒性分级标准评价不良反应,观察患者的总生存时间(OS)和疾病进展时间(TTP).结果 50例患者均可评价疗效,其中疾病稳定(SD)28例,疾病稳定率为56.0%;疾病进展(PD)22例,占44.0%;无完全缓解(CR)和部分缓解(PR)患者.中位随访时间为15个月,随访期间共有17例患者死亡,全组患者的中位TTP为4个月,中位OS为14个月.索拉非尼治疗不能手术的原发性HCC患者的不良反应为皮肤损害、腹泻、高血压、脱发、骨髓抑制和肝功能损害等,大多为Ⅰ～Ⅱ级,经对症处理或调整用药剂量后多可恢复.单因素分析结果显示,有无远处转移是影响HCC患者TTP的主要因素.结论 索拉非尼可有效治疗不能手术的原发性HCC,有无远处转移是影响HCC患者TTP的主要因素.     

三维适形放疗联合化疗治疗食管癌上纵隔淋巴结转移的疗效分析

目的:探讨三维适形放疗联合化疗治疗食管癌上纵隔淋巴结转移的近期疗效.方法:回顾性分析15例食管癌上纵隔淋巴结转移患者.转移灶直径<3 cm 4例, 3～5 cm 8例,>5 cm 3例,15例中右上纵隔13例,左上纵隔2例.三维适形放疗采用常规分割,1.8～2 Gy/次,5次/周,总剂量50～64 Gy(既往做过放疗的给予50 Gy), 5～7周完成.全身化疗采用顺铂(DDP) 30 mg/m2,d1～d3;亚叶酸钙(LV)500 mg/m2,d1～d5;5-氟尿嘧啶(5-FU) 500 mg/m2,d1～d5,均静脉滴入,21 d为1个周期,放疗前化疗1个周期,共4～6个周期.结果:治疗后1个月复查,病灶达CR者9例,病灶达PR者4例,无进展病例.6个月、1年生存率分别为100%、86.7%.结论:食管癌上纵隔淋巴结转移进行三维适形放射治疗联合PF方案化疗,此方案患者可耐受,方法可行.     

肝动脉栓塞化疗后射频消融联合酒精消融对原发性肝癌的疗效评价

目的　探讨肝动脉栓塞化疗(TACE)后,CT导向下射频消融(RFA)联合无水乙醇消融(PEI)对原发性肝癌(HCC)的治疗效果。方法　经病理、AFP或典型影像学诊断证实的HCC 1 5 0例,每例肝内的病灶数目<3个,病灶大小3.1～7.9cm ,平均直径5 .5cm。全部患者按就诊单双日分为对照组和联合组。对照组74例,TACE后2周行单纯RFA ;联合组76例,TACE后2周行射频消融,间隔2 0～30d后再行PEI。结果　对照组的完全坏死率为75 .8%,联合组为89.5 %,两组间差异有统计学意义(P <0 .0 5 )。结论　HCC患者经TACE后,行CT导向下RFA联合PEI的疗效明显优于单纯RFA。     

西妥昔单抗联合化疗初始治疗转22例移性结直肠癌的近期疗效观察

目的:观察西妥昔单抗联合含奥沙利铂或伊立替康方案初始治疗转移性结直肠癌及其可评价病灶的近期疗效及全身副反应。方法:选取2007年6 月1 日至2008年6 月30日本院22例经病理学确诊的转移性结直肠癌患者,随机分两组,应用西妥昔单抗（爱必妥）:首剂400mg/m2,次周250mg/m2,每周1 次,分别联合FOLFIRI 方案（CPT-11180mg/m2,d1,CF400mg/m2,d1,5-FU 400mg/m2,静脉推注d1,5-FU 2.4mg/m2连续输注46h,d1～2,2 周重复一次）和mFOLFOX6（L-OHP85mg/m2,d1,CF400mg/m2,d1,5-FU 400mg/m2,静脉推注,d1,5-FU 2.4mg/m2连续输注46h,d1～2,2 周重复一次）行靶向治疗联合化疗,每4 周评价疗效。结果:全组有21例可评价疗效,部分缓解（PR）12例,疾病稳定（SD）6 例,有效率（RR）57.1% ,疾病控制率（CR+PR+SD ）85.7% ,其中2 例肝转移患者PR后行肝脏射频治疗,2 例行Ⅰ期转移灶切除术,转移灶转化可切除率23.5% ,使原来无法切除的转移瘤得以切除,主要不良反应为皮肤痤疮样皮疹和骨髓抑制。结论:西妥昔单抗联合含奥沙利铂或伊立替康方案初始治疗转移性结直肠癌安全有效,并一定程度上转化肝转移病灶,提高结肠癌肝转移手术切除率,可能改善预后,这将为转移性结直肠癌新的治疗策略提供有力证据。      

以索拉非尼为基础治疗晚期肝细胞癌的疗效和不良反应临床观察

背景与目的:多激酶抑制剂索拉非尼因SHARP(Sorafenib HCC Assessment RandomizedProtocol)和ORIENTAL(Sorafenib in Patients in Asia-pacific Region with Hepatocellular Carcinoma)2项Ⅲ期临床试验证实能显著改善无进展生存期(progress free survival,PFS)和延长疾病进展时间(time toprogression,TTP)和总生存期(overall survival,OS),2008年被批准为晚期肝细胞癌的治疗。本研究观察索拉非尼单用或联合TACE治疗30例晚期肝细胞癌的疗效和不良反应。方法:选择2009年3月—2011年1月,符合晚期原发性肝癌临床或病理诊断的患者30例,每次口服索拉非尼400 mg,每日2次,至少口服2个月以上,其中20例联合1～9次TACE,10例单用索拉非尼治疗。按RESIST标准,每2个月评价疗效,随访TTP和OS。结果:30例患者部分缓解(PR)3例,疾病稳定(SD)16例,疾病进展(PD)11例,临床获益率(clinical benefit rate,CBR)为63.3%。其中10例单用索拉非尼组PR 1例,SD 5例,PD 4例,CBR为60.0%;20例联合治疗组PR 2例,SD 11例,PD 7例,CBR为65.0%。27例患者生存3个月,24例6个月,21例9个月,9例1年以上,全组TTP为7个月,OS为9个月。联合组患者TTP为7个月,OS为14个月,单用索拉非尼组患者TTP为6个月,OS为9个月,差异无统计学意义(P>0.05)。患者用药1～2周开始出现不良反应,手足皮肤反应23例,腹泻24例,高血压14例,乏力24例,脱发9例,出现3度不良反应10例,给予对症治疗后,均能完成治疗。结论:索拉非尼联合TACE治疗较单用索拉非尼治疗可延长患者的TTP和OS,但两组差异无统计学意义(P>0.05)。两组患者不良反应可耐受,不良反应发生率差异无统计学意义(P>0.05)。     

TACE联合胸腺肽α1治疗不可切除性肝细胞肝癌

目的评估经动脉化疗栓塞(trascatheter arterial chemoembolization,TACE)联合胸腺肽α1(α1)治疗不可切除性肝细胞肝癌(HCC)的疗效。方法将64例不可切除性HCC患者分成2组,TACE+Tα1治疗组32例,予TACE治疗后每2天皮下注射1.6 mg Tα1,持续24周;单纯TACE治疗组32例,术后予对症支持治疗。通过肿瘤反应、疾病进展时间评估疗效。结果 TACE+Tα1组:肿瘤反应率62.5%、中位疾病进展时间31周;单纯TACE组:肿瘤反应率46.9%、中位疾病进展时间19周,两组比较肿瘤反应率差异无统计学意义(P=0.209),中位疾病进展时间差异有统计学意义(P=0.03)。结论TACE联合Tα1治疗不可切除性HCC可延长中位疾病进展时间,提高患者生活质量,但肿瘤反应率未见改善。     

三维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:观察三维立体适形放射治疗(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,1次/d,5d/周。肿瘤剂量30～54Gy,总疗程3～6个周。结果:46例患者中,部分缓解8例,稳定35例,进展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、放疗前肝硬化Child-Pugh分级和肿瘤照射剂量对生存率的影响差异有统计学意义。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。     

Sorafenib in combination with transarterial chemoembolization and bronchial arterial chemoinfusion in the treatment of hepatocellular carcinoma with pulmonary metastasis

Aim: Hepatocelluar carcinoma (HCC) with pulmonary metastasis is considered incurable. This study addresses the efficacy of the combination of systemic therapy using sorafenib and local treatment using transarterial chemoembolization (TACE) for intrahepatic and bronchial transarterial chemoinfusion (TAI) for pulmonary lesions for this condition. Methods: In all, 52 HCC patients with pulmonary metastasis were treated with sorafenib and TACE/TAI for intrahepatic and intrapulmonary lesions. Response to treatment, progression‐free survival (PFS), overall survival (OS) and treatment‐induced adverse effects were analyzed. Results: With a median follow‐up time of 11.4 months, radiologically confirmed complete response (CR), partial response (PR), stable disease and disease progression for intrahepatic disease were observed in 0, 22, 23 and seven patients, respectively; radiologically confirmed CR, PR, stable disease and disease progression observed for intrapulmonary lesions were in 1, 8, 25 and 18 patients, respectively. Median OS and PFS was 12.0 and 10.0 months, respectively. Median OS of patients who achieved response (i.e., CR + PR + stable disease) in their gross lesion(s) was 14.0 and 13.0 months, respectively, as compared to 4.0 and 3.0 months for patients who progressed (P < 0.003). Significant prognosticators for OS and PFS included performance status, Barcelona Clinic Liver Cancer stage and response to treatment. The combined treatment strategy was well tolerated. Conclusion: The combination of sorafenib, TACE and TAI produced median OS and PFS of 12 and 10 months, respectively, in HCC patients with lung metastasis. The outcomes of patients who achieved a response to their gross lesions were significantly better than those who had disease progression. Further investigation is warranted to test the efficacy of this treatment combination.     

Efficacy of percutaneous transhepatic portal embolization for unresected cases of hepatocellular carcinoma

We reported an efficacy of percutaneous transhepatic portal embolization (PTPE) for three patients with hepatocellular carcinoma (HCC) who did not receive hepatic resection. All three patients, who had HCCs in the right hepatic lobe, were given transarterial chemoembolization (TACE) and PTPE in the aim of hepatic resection. However, hepatic resection was not performed because of the refusal of operation or insufficient hypertrophy of the remnant liver. Primary lesions were well controlled by TACE in all of the cases. We recognized new HCC lesions of the liver in the clinical courses, but all tumors appeared to be in the post-PTPE area only. A possibility of prevention for transportal intrahepatic dissemination by PTPE was considered. We conclude that combination therapy including PTPE for HCC patients with tumors in the limited area is useful for the improvement of their prognosis.     

Interim analysis of START: Study in asia of the combination of TACE (transcatheter arterial chemoembolization) with sorafenib in patients with hepatocellular carcinoma trial

Transarterial chemoembolization (TACE) represents a first‐line noncurative therapy for hepatocellular carcinoma (HCC). Sorafenib, a multikinase inhibitor, has been shown to be effective and safe monotherapy in patients with advanced HCC and the current study reports the interim results of a prospective Phase II, open label, trial investigating the safety and efficacy of the combination of sorafenib and conventional TACE in patients from the Asia‐Pacific region with intermediate HCC. Patients with histologically or clinically diagnosed HCC were treated with conventional TACE followed by sorafenib 4 to 7 days later. TACE was performed by selective transarterial chemotherapy in the vessels feeding the tumor with an emulsion of lipiodol (5–20 ml) and doxorubicin (30–60 mg) followed by embolization with absorbable particles (gel foam). TACE/sorafenib cycles were repeated every 6–8 weeks. Primary objectives were to evaluate the safety and tolerability, in addition to the efficacy of TACE combined with sorafenib for HCC. A total of 147 patients were included in the intention‐to‐treat analysis and received at least one dose of sorafenib. Gastrointestinal AEs were reported by 62.6% of patients while 57.8% reported skin AEs although most were mild to moderate. The mean number of cycles undertaken was 2.1 and 63.3% of patients achieved either partial response or stable disease. Clinically, the disease control rate was 91.2% while the overall response rate was calculated as 52.4%. Our study shows that concurrent sorafenib and TACE therapy is safe and effective with no unexpected side effects.     

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.     

The combination of transcatheter arterial chemoembolization and sorafenib is well tolerated and effective in Asian patients with hepatocellular carcinoma: Final results of the START trial

This phase II, investigator‐initiated, prospective single‐arm multinational study ( ClinicalTrials.gov registration NCT00990860) evaluated sorafenib in combination with doxorubicin‐based transarterial chemoembolization (TACE) in patients with intermediate‐stage, unresectable hepatocellular carcinoma (HCC). Patients with histologically or clinically diagnosed HCC received TACE with interrupted dosing of sorafenib (sorafenib discontinued for 3 days before and 4–7 days after TACE). TACE/sorafenib cycles were repeated every 6–8 weeks. Primary and secondary objectives were, respectively: to evaluate the safety and tolerability of TACE combined with sorafenib, and also their efficacy. The full analysis set comprised 192 patients (mean age 56.1 years). Most were male (87.0%), Eastern Cooperative Oncology Group (ECOG) score 0 (81.8%), Child‐Pugh A (91.8%) and Barcelona Clinic Liver Cancer (BCLC) stage B (81.5%); 81.2% had chronic hepatitis B. Combined TACE/sorafenib was well tolerated, with only 8.1% of patients discontinuing owing to adverse events (AEs). The most common grade ≥3 AEs were palmar‐plantar erythrodysesthesia syndrome (15.1%) and decreased platelet count (10.9%). Serious AEs (SAEs) occurred in 52 patients during the study; however, only four were considered related to sorafenib. A mean of 2.7 TACE cycles were administered and 52.6% of patients achieved complete response in target lesions; 16.8% achieved partial response, and 5.8% had progression of disease as their best response, evaluated by modified RECIST. Median progression‐free survival and time to progression were 384 and 415 days, respectively, and the estimated 3‐year overall survival was 86.1%. This study suggests that the combination of TACE and sorafenib is well tolerated and efficacious; the interrupted sorafenib dosing schedule may have contributed to a considerably lower AE profile than observed in other combination trials.     

The possible role of sorafenib as a part of the multimodal treatment for hepatocellular carcinoma

The role of sorafenib is unclear in multimodal treatment for hepatocellular carcinoma (HCC). We analyzed patients who underwent multimodal treatment including surgical operation for advanced HCC after administration of sorafenib. A 79- year-old man underwent extended right hepatectomy for Stage III huge HCC. Three years later, multiple recurrences observed in the liver, and an extrahepatic tumor was diagnosed. Peritoneal seeding was suspected, thus we decided to start a sorafenib administration. After 11 months, new intrahepatic lesions were detected, but extrahepatic tumor was unchanged. We considered the extrahepatic tumor was solitary and resectable, and new lesions in the liver were still treatable, then we attempted a surgical treatment with partial hepatectomy and ablation therapy. The tumor was successfully resected, and residual viable tumors were treated by radiofrequency ablation. The patient remains alive without recurrence at 7 months. We could perform a surgical treatment for another 2 patients with sorafenib treatment. These results suggested that there are cases of advance HCC in which multimodality treatment including surgical treatment can be achieved after sorafenib administration.     

Effect of rapamycin alone and in combination with sorafenib in an orthotopic model of human hepatocellular carcinoma

PURPOSE: Novel therapeutic strategies are needed to prevent the tumor recurrence or metastasis after liver transplantation for hepatocellular carcinoma (HCC). This study was to investigate the effect of rapamycin, alone and in combination with sorafenib, on HCC in vivo. EXPERIMENTAL DESIGN: Xenograft of a highly metastatic human HCC tumor (LCI-D20) was used to evaluate primary tumor growth and lung metastasis after treatment with rapamycin alone or in combination with sorafenib. Tumor cell proliferation was determined by Ki-67 immunostaining. To detect tumor cell apoptosis, the terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labeling assay was used. Tumor angiogenesis was investigated by using a monoclonal anti-CD31 antibody. A vascular endothelial growth factor ELISA kit was used to measure vascular endothelial growth factor protein levels in the mice serum. RESULTS: Rapamycin, alone and in combination with sorafenib, strongly inhibited primary tumor growth and lung metastases in LCI-D20 model. Furthermore, the combination therapy significantly enhanced the effect of antitumor on primary tumor growth compared with single treatment with either rapamycin (P < 0.001) or sorafenib (P < 0.001). Rapamycin alone inhibited HCC cell proliferation, induced apoptosis, and decreased tumor angiogenesis. Nevertheless, the combination therapy showed a significant inhibition of tumor cell proliferation (P < 0.05). Additionally, the combination therapy also further enhanced suppression of tumor cell angiogenesis compared with rapamycin treatment (P < 0.01). However, the induction of apoptosis in combination therapy group was not significantly higher than in the rapamycin-treated group (P > 0.05). CONCLUSIONS: The combination therapy of rapamycin and sorafenib could be a new and promising therapeutic approach to the treatment of HCC and prevention of HCC recurrence after liver transplantation.     

射频消融在治疗肝癌合并肝动脉-门静脉分流中的应用价值

目的评价射频消融(RFA)对肝癌合并肝动脉-门静脉分流(APS)的治疗价值。方法对34例肝癌合并APS患者,针对APS和肿瘤行射频消融治疗,2周后行肝增强CT或MRI扫描并行TACE治疗。比较肿瘤消融、坏死效果及APS分流道封闭情况。结果射频消融术后15例中央型APS完全消失4例,分流减少8例,3例无明显变化;10例肝段型APS,有3例术后APS消失,5例好转,2例无变化;周围型9例,术后消失5例,好转4例。38个消融病灶中,完全坏死11个病灶,14个病灶坏死面积超过50%,坏死50%以下有8个病灶,4个病灶RFA术后强化面积无变化,1个病灶进展。术后随访3～12月,3、6、9、12月累计生存率分别为100%、94.1％、82.4％、73.5％。结论射频消融联合TACE是治疗肝癌合并肝动脉-门静脉分流的安全有效的方法。