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局部三维适形放疗联合经动脉化疗栓塞治疗Ⅲ期肝细胞癌患者的研究

Study of local three-dimensional conformal radiotherapy combined with transcatheter arterial chemoembolization for patients with stage III hepatocellular carcinoma.

作者信息

Li Baosheng, Yu Jinming, Wang Liying, Li Chengjun, Zhou Tao, Zhai Limin, Xing Ligang

机构信息

Department of Radiation Oncology, Shandong Cancer Hospital & Institute, Jinan, Shandong Province, China.

出版信息

Am J Clin Oncol. 2003 Aug;26(4):e92-9. doi: 10.1097/01.COC.0000077936.97997.AB.

Abstract

The purpose of this study was to evaluate treatment-related toxicity, outcome, patterns of failure, and prognostic factors for patients with stage III unresectable hepatocellular carcinoma (HCC) treated with a combination of local 3-dimensional conformal radiotherapy (3D-CRT) and transcatheter arterial chemoembolization (TACE) under the support of G-CSF. From October 1997 to August 2001, 45 patients with stage III unresectable hepatocellular carcinoma underwent transcatheter arterial chemoembolization with local 3D-CRT. Twenty-seven patients were classified as having stage IIIA disease according to the American Joint Committee on Cancer (AJCC) staging system and 18 were classified as stage IIIB. The mean diameter of the treated hepatic tumor was 8.5 cm. Before 3D-CRT, 2 cycles of transcatheter arterial chemoembolization were prescribed. Forty-eight hours later, the G-CSF was prescribed for 5 days after the completion of every TACE. With the interval of 10 to 14 days after the second cycle of TACE, 3D-CRT was prescribed to all patients with a total dose of 50.4 Gy at 1.8 Gy per fraction 5 days per week. After the completion of 3D-CRT, the additional 2 cycles of TACE were given. All patients were monitored for treatment-related toxicity, outcome, patterns of failure, causes of death, and prognostic factors. Forty-two of 45 patients were treated smoothly with the primary schedule. In a median follow-up period of 27 months, 22 patients were alive and 23 were dead. Progressive disease occurred in 28 patients, including local recurrence alone (4 patients), distant metastases with local recurrence (8 patients), and distant metastases alone (16 patients). Nine patients developed radiation-induced liver disease (RILD). Three patients had treatment-related gastrointestinal bleeding. There were 2 treatment-related deaths, including 1 from RILD and 1 from gastrointestinal bleeding. Complete regression (CR) was observed in 6 patients, partial regression (PR) in 35 patients, and stable disease (SD) in 4 patients. The median overall survival duration from treatment was 23.5 months with a 1-year overall survival rate of 68.5%, a 2-year survival rate of 48.3%, and a 3-year survival rate of 22.6%. The median freedom from progressive disease survival duration from treatment was 25 months with 1-year, 2-year, and 3-year progression-free survival rates of 76.2%, 56.8%, and 42.4%, respectively. The stage of HCC, regional lymph node status, portal vein thrombosis, pretreatment alpha-fetoprotein level (AFP), and tumor size affected the treatment outcomes significantly. Therefore, for patients with stage III unresectable hepatocellular carcinoma, combined local 3D conformal radiotherapy with transcatheter arterial chemoembolization under the support of G-CSF is an effective treatment protocol. Further research is required to decrease distant metastases and to determine the safe irradiation dose-volume.

摘要

本研究的目的是评估在粒细胞集落刺激因子(G-CSF)支持下,采用局部三维适形放疗(3D-CRT)联合经动脉化疗栓塞术(TACE)治疗Ⅲ期不可切除肝细胞癌(HCC)患者的治疗相关毒性、疗效、失败模式及预后因素。1997年10月至2001年8月,45例Ⅲ期不可切除肝细胞癌患者接受了局部3D-CRT联合经动脉化疗栓塞术治疗。根据美国癌症联合委员会(AJCC)分期系统,27例患者被分类为ⅢA期疾病,18例被分类为ⅢB期。治疗的肝肿瘤平均直径为8.5 cm。在进行3D-CRT之前,规定进行2个周期的经动脉化疗栓塞术。48小时后,在每次TACE完成后给予G-CSF,持续5天。在第二个TACE周期后间隔10至14天,对所有患者进行3D-CRT,总剂量为50.4 Gy,每周5天,每次分割剂量为1.8 Gy。在3D-CRT完成后,再给予2个周期的TACE。对所有患者监测治疗相关毒性、疗效、失败模式、死亡原因及预后因素。45例患者中有42例按原计划顺利完成治疗。在中位随访期27个月时,22例患者存活,23例患者死亡。28例患者出现疾病进展,包括单纯局部复发(4例)、远处转移合并局部复发(8例)和单纯远处转移(16例)。9例患者发生放射性肝病(RILD)。3例患者出现治疗相关的胃肠道出血。有2例治疗相关死亡,包括1例死于RILD,1例死于胃肠道出血。6例患者观察到完全缓解(CR),35例患者部分缓解(PR),4例患者疾病稳定(SD)。治疗后的中位总生存时间为23.5个月,1年总生存率为68.5%,2年生存率为48.3%,3年生存率为22.6%。治疗后的中位无进展生存期为25个月,1年、2年和3年无进展生存率分别为76.2%、56.8%和42.4%。HCC分期、区域淋巴结状态、门静脉血栓形成、治疗前甲胎蛋白水平(AFP)和肿瘤大小对治疗结果有显著影响。因此,对于Ⅲ期不可切除肝细胞癌患者,在G-CSF支持下局部3D适形放疗联合经动脉化疗栓塞术是一种有效的治疗方案。需要进一步研究以减少远处转移并确定安全的照射剂量体积。

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