肝动脉化疗栓塞序贯调强适形放射治疗联合治疗原发性肝癌

背景与目的:不能手术的原发性肝癌(primary hepotocellular carcinoma,PHC)的传统治疗手段是肝动脉化疗栓塞(transarterial chemo-embolization,TACE);TACE后对肿瘤局部实施高剂量放射治疗,有望降低TACE后周边肿瘤的复发。适形放射治疗(conformal radiation treatment,CRT)与调强适形放射治疗(intensity modulated radia-tion treatment,IMRT)技术使对肝脏肿瘤进行高剂量照射成为可能。本文旨在评价TACE序贯IMRT联合治疗原发性肝癌患者的耐受性及疗效。方法:1999年9月-2004年12月共治疗PHC72例,UICC1997肝癌分期标准为T2期14例,T3期39例,T4期19例;2001年广州分期Ⅰb期4例,Ⅱa期35例,Ⅱb期20例,Ⅲa期13例。TACE经股动脉插管至肝固有动脉或其分支,注入5～20ml顺铂、表柔比星与40%碘化油混悬液,1～2mm明胶海绵栓塞肝动脉,4周1次,有门静脉癌栓不予栓塞。IMRT应用CORVUS3.0/5.0逆向治疗计划系统及MIMiC多叶调强准直器,(1.8～5.0)Gy/次,(3～5)次/周;总剂量(34.5～58.8)Gy/10-25次,L-Q方程换算等效常规照射剂量为(42～70)Gy;常规保肝治疗。结果:CR3例,PR53例,有效率(CR PR)77.78%(56/72),中位生存时间24个月,1、2、3、4、5年生存率分别为72.72%、47.22%、28.25%、16.89%、12.89%;一过性转氨酶升高20.83%(15/72),十二指肠溃疡2.78%(2/72)。结论:TACE序贯IMRT联合治疗原发性肝癌,患者耐受性良好,无严重的远期并发症。显示了较好的疗效。     

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。     

三维适形放疗联合肝动脉化疗栓塞治疗原发性肝癌的疗效

目的探讨三维适形放疗（3DCRT）联合肝动脉化疗栓塞（TACE）治疗原发性肝癌的疗效、不良反应及生存率。方法对30例原发性肝癌患者先行TACE,将顺铂60～100 mg、丝裂霉素10～20 mg、与40%碘化油20 ml混悬液,注入肝动脉栓塞治疗2～4次。化疗停3～4周后再行3DCRT,采用6MV、X射线治疗,单次剂量1.8～2.0 Gy、每周5次,总剂量45～55 Gy。结果近期有效率为83.3.%,1、2年生存率分别为76.7%、53.3%。结论三维适形放疗联合肝动脉化疗栓塞是非手术治疗原发性肝癌的有效治疗方案。     

肝动脉栓塞化疗联合三维适形放疗治疗原发性肝癌的临床分析

目的 探讨肝动脉栓塞化疗( TACE)联合三维适形放疗( 3DCRT)治疗原发性肝癌的有效性和耐受性.方法 回顾性分析采用TACE联合3DCRT治疗的53例原发性肝癌,评价其近期有效率,远期总生存率,毒副反应,通过COX回归分析其预后因素.结果 总有效率62.3%,1、2、3年总生存率和中位生存时间分别为67.9%、32.7%、11.5%和19个月.多因素分析显示门静脉有无癌栓和放疗剂量是影响预后的独立因素.结论 3DCRT联合TACE治疗原发性肝癌是一种有效的综合治疗手段,但治疗前需准确评估肝功能状态及其耐受性.     

单纯肝动脉栓塞化疗和三维适形放疗联合肝动脉栓塞化疗对原发性肝癌的疗效比较

目的比较单纯肝动脉栓塞化疗和肝动脉栓塞化疗联合三维适形放疗对原发性肝癌的疗效。方法 48例原发性肝癌患者,随机分为单纯TACE组和TACE联合3DCRT组,按照WHO肿瘤评定标准评价近期疗效,以3年内生存率为指标评价远期疗效。结果 TACE组24例患者中完全缓解（CR）0例,部分缓解（PR）13例,总有效率（CR＋PR）为54.17%。TACE联合3DCRT组24例患者中完全缓解（CR）1例,部分缓解（PR）16例,总有效率（CR＋PR）为70.83%。TACE组1、2、3年生存率分别为58.33%、33.33%和16.67%;TACE联合3DCRT组1、2、3年生存率分别为79.17%、54.17%和25.00%。结论 TACE联合3DCRT组疗效优于TACE组。     

肝动脉栓塞化疗治疗中晚期肝癌的临床研究

目的：研究肝动脉拴塞化疗治疗中晚期肝癌的疗效。方法：对118例经肝动脉栓塞化疗治疗的中晚期肝癌患者评价疗效并随访2a以上，观察其生存率。结果：完全缓解8例，部分缓解49例。轻微缓解44例，无变化17例。有效率达85．6％。1a生存率为66．9％，2a生存率为31．4％。结论：肝动脉栓塞化疗治疗中晚期肝癌疗效确切，副作用较少，易于在基层医院推广。     

肝动脉栓塞化疗联合立体定向放射治疗原发性肝癌的疗效分析

目的:分析肝动脉栓塞化疗（TACE）联合立体定向放射治疗（SBRT）不能手术的原发性肝癌的疗效及毒副反应。方法:96例不能手术的原发性肝癌患者,TACE联合SBRT治疗44例（研究组）,单纯TACE治疗52例（对照组）。TACE灌注化疗药物为:氟尿嘧啶（5-FU）（1 000~1 500）mg和/或顺铂［DDP（40~60）mg］,表阿霉素（E-ADM）（30~50）mg,栓塞剂为超乳化碘油（3~18）ml。SBRT采用月亮神立体定向伽玛射线旋转聚焦全身放射治疗系统,≥50%等剂量线包绕PTV,单次剂量3~6Gy,5次/周,照射总量30~50Gy。结果:研究组和对照组的TACE平均次数分别为2.0（1~6）和3.6（1~7）。中位生存期分别为18.1个月和10.6个月。两组2年局部控制率分别为42.5%、32.8%,3年局部控制率分别为35.8%、22.5%,两组比较有显著的统计学意义（P=0.044,P=0.040）。2年生存率分别为40.5%、29.2%,3年生存率分别为32.2%、20.3%,2年、3年总生存率比较两组均有统计学差异（P=0.048,P=0.032）。研究组发现2例放射诱发的肝病。结论:TACE联合SBRT比单纯TACE对不能手术的原发性肝癌治疗疗效好,毒副反应未增加。     

立体定向适形放疗联合TACE治疗原发性肝癌的疗效观察

目的:评价立体定向适形放疗联合经肝动脉栓塞化疗治疗原发性肝癌的临床疗效.方法: 将62例中晚期肝癌患者分为R+T组(32例)与R组(30例),R+T组行立体定向适形放疗联合经导管肝动脉化疗栓塞术治疗,R组行单纯立体定向适形放疗,观察近期疗效与不良反应.结果: R+T组有效24例,有效率75.0%,R组有效15例,有效率50.0%,两者比较差异具有显著性,不良反应比较无显著性差异. 结论: 新型立体定向放疗联合TACE是治疗中晚期肝癌的有效手段.     

立体定向适形放疗联合TACE治疗原发性肝癌的疗效观察

目的：评价立体定向适形放疗联合经肝动脉栓塞化疗治疗原发性肝癌的临床疗效。方法：将62例中晚期肝癌患者分为R＋T组（32例）与R组（30例）,R＋T组行立体定向适形放疗联合经导管肝动脉化疗栓塞术治疗,R组行单纯立体定向适形放疗,观察近期疗效与不良反应。结果：R＋T组有效24例,有效率75．0％,R组有效15例,有效率50．0％,两者比较差异具有显著性,不良反应比较无显著性差异。结论：新型立体定向放疗联合TACE是治疗中晚期肝癌的有效手段。     

Clinical study of transarterial chemoembolization combined with 3-dimensional conformal radiotherapy for hepatocellular carcinoma

Background

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Monotherapy is not very effective for intermediate or advanced stage HCC. Efficacy of combined therapy using transarterial chemoembolization (TACE) with three-dimensional conformal radiotherapy (3-DCRT) for advanced HCC should be evaluated.

Methods

HCC patients were selected from our patient database. The sequence of treatments that patients underwent was several courses of TACE followed in 2-4 weeks by 3-DCRT. The median tumor irradiation dose was 44Gy. Toxicity, tumor response, and overall survival rate were analyzed.

Results

140 HCC patients were followed up by the last follow-up time. Among these patients, hepatic toxicities due to treatment were notable in 15 cases. Gastrointestinal bleeding after the overall treatment occurred in 3 cases. Leukopenia of grade III was detected in 1 case. Radiation-induced liver disease (RILD) was observed in 3 patients. Among 140 patients, 27, 97, and 16 cases achieved partial response, stable disease, and progressive disease, respectively. The overall survival rates of 1-year, 3-years, and 5-years were 66%, 29%, and 13%, respectively, with a median survival time of 18 months. Both Child-Pugh grade and radiation dose were determined to be independent predictors for overall survival from multivariate analysis.

Conclusion

The combined modality of TACE and 3-DCRT is a promising treatment for unresectable HCC. A large-scale, prospective randomized trial should be performed to confirm the utility of this combined therapy.     

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.     

粒子植入放疗联合肝动脉化疗栓塞治疗肝癌的临床研究

目的观察局部125I粒子植入放疗联合肝动脉化疗栓塞(TACE)治疗肝细胞性肝癌疗效和患者耐受性。方法56例患者先采用TACE治疗1-3次,再行CT引导下125I粒子植入放疗。125I粒子植入12周后采用世界卫生组织标准评价疗效,采用美国国立癌症研究所毒性标准和美国放疗肿瘤组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56例中部分缓解18例,稳定36例,进展2例。全组中位生存时间31个月,1、3年生存率分别为88%、54%。1、3年局部控制率分别为93%、70%。1、3年远处转移率分别为9%、13%。单因素分析表明T分期、门脉癌栓、放疗前肝硬化Child-pugh分级、肿瘤数目和125I粒子空间排列对生存率有影响。多因素分析显示125I粒子空间排列、肿瘤数目和肝硬化Child-pugh分级是患者预后独立影响因素。5例发生急性肝脏毒副反应,1级2例,3级3例。9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,8例表现为恶性、呕吐。10例出现1、2级外周血白细胞降低。2例出现放射性肝病。结论局部125I粒子植入放疗联合TACE综合治疗安全、有效,值得进一步研究。     

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。     

肝动脉栓塞联合三维放射治疗肝癌的疗效评价

目的 评估经首次导管化疗栓塞(TACE)后,碘油栓塞不完全的中晚期肝细胞癌患者序贯适形外放射治疗的疗效及毒副作用。方法 2008年1月—2010年1月,纳入首次栓塞不完全的50例中晚期肝细胞癌患者,随机分两组,25例患者依据病情进行2~3次单纯TACE,25例序贯采用三维适型外放射补充治疗。测量肿瘤大小变化评价肿瘤的反应,评估治疗毒副作用。结果 单纯TACE组治疗前后平均肿瘤直径分别为(8.37±9.15)cm和(4.22±5.66)cm;TACE放疗组治疗前后平均肿瘤直径分别为(8.65±6.89)cm和(3.86±4.32)cm。两组治疗前后比较差异具有统计学意义,两组间比较无统计学意义。TACE放疗组总有效率为52%,完全反应16%,部分反应36%。两组患者12个月生存率分别为48%和64.0%,差异具有统计学意义(P＜0.05)。没有出现三级及更高级别的毒副作用。结论 对首次栓塞不完全的肝细胞癌患者,序贯采用三维适型外放射补充治疗能有效的提高患者的生存率,且毒副作用可以耐受。     

肝动脉栓塞化疗联合放疗治疗不能手术的原发性肝癌的临床观察

目的　观察肝动脉栓塞化疗（ＴＡＣＥ）联合直线加速器或全身伽玛刀治疗不能手术的原发性肝癌（ＰＨＣ）的疗效及毒副反应。方法　２００５年７月至２００８年６月,１０８例不能手术的ＰＨＣ患者中５０例行ＴＡＣＥ联合直线加速器放疗（加速器组）,５８例行ＴＡＣＥ联合全身伽玛刀放疗（伽玛刀组）。ＴＡＣＥ灌注化疗药物包括丝裂霉素（ＭＭＣ）１０～２０ｍｇ、氟尿嘧啶（５-ＦＵ）１０００～１５００ｍｇ、表阿霉素（Ｅ-ＡＤＭ）３０～５０ｍｇ,栓塞剂为４０％超液态碘化油５～２０ｍｌ。直线加速器治疗用６ＭＶ Ｘ,９５％等剂量线包绕ＰＴＶ,４０～６０Ｇｙ／１５～２５ｆ,３～５ｆ／周;伽玛刀治疗用月亮神立体定向伽玛射线旋转聚焦全身放射治疗系统（ＬＵＮＡ-ＴＭ-２６０）,４０％ ～６０％等剂量线包绕ＰＴＶ,单次剂量３～６Ｇｙ,３～５ｆ／周,照射总量３０～５０Ｇｙ。联合应用ＴＡＣＥ为１～３个疗程。结果　加速器组及伽玛刀组的中位生存期分别为１４个月和１６个月,中位肿瘤进展时间（ＴＴＰ）分别为７.６个月和８.１个月;２年局部控制率分别为４５.４％和４３.６％（χ^２ ＝０.０２０,Ｐ＝０.８８７）,３年局部控制率分别为３６.５％和３７.９％（χ^２ ＝０.０４０,Ｐ＝０.８４１）;２年生存率分别为４１１％和３９６％（χ^２ ＝０.０２１,Ｐ＝０.８８５）,３年生存率分别为３４.３％和３０.２％（χ^２ ＝０.３６８,Ｐ＝０.５４４）。加速器组中出现１例放射诱发的肝病,伽玛刀组未见相关病例。结论　直线加速器和伽玛刀联合ＴＡＣＥ治疗ＰＨＣ均安全可靠,疗效相当。     

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.     

低分割三维适形放疗联合肝动脉化疗栓塞治疗中晚期原发性肝癌的疗效评价

目的:评价低分割三维适形放疗(3D-CRT)联合肝动脉化疗栓塞(TACE)对中晚期肝癌综合治疗效果。方法:对确诊的110例中晚期肝癌患者随机分成两组,低分割组55例,先行TACE治疗后再行3D-CRT,6～8Gy/次,3次/周,大体肿瘤体积(GTV)剂量为48～64Gy,总周期3～4周;常规分割组55例,行TACE治疗后再行3D-CRT,1.8～2Gy/次,5次/周,GTV剂量为60～70Gy,总周期6～7周。比较两组的毒副反应和疗效。结果:低分割组CR26例,PR24例;常规分割组CR21例,PR27例。两组比较差异无统计学意义,χ2=0.485,P=0.785。低分割组1、2和3年总体生存率分别为78.2%、50.9%和25.9%,常规分割组分别为65.5%、32.7%和15.0%,χ2=4.123,P=0.042;低分割组中位生存期为27个月,常规分割组为18个月。结论:低分割3D-CRT联合TACE较常规分割明显提高中晚期肝癌的远期疗效,治疗相关毒副反应增加,但能耐受。