Study of Hypofractionated Three-Dimensional Conformal Radiotherapy Combined With Trancather Arterial Chemoembolization for advanced Hepatocellular Carcinoma

　　WANG Chuan-xi, WU De-hua, SUN ai-min, CHEN Long-hua

　　Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China山东省立医院肿瘤中心王传玺

　　【摘要】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，照射方式：6-8Gy/次，3次/周，大体肿瘤体积(GTV)剂量为48-64 Gy，总疗程2-3周；常规分割组55例行TACE 治疗后再行3D-CRT，照射方式：1.8-2Gy/次，5次/周，GTV剂量为60-70 Gy，总疗程6-7周。比较两组的毒副作用和疗效。结果: 低分割组26例为CR，24例为PR；常规分割组21例为CR，27例为PR。两组比较差异无统计学意义(χ2 =0.485 , p= 0.785 )。1、2、3年的总体生存率低分割组为78.2%、50.9%、25.9%，常规分割组为65.5%、32.7%和15%(χ2=4.123, p=0.042)；中位生存期低分割组为27月, 常规分割组为18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，治疗相关毒副作用增加，但能耐受。

　　[Abstract] Objective: To evaluate the efficacy of hypofractionated three-dimensional conformal radiotherapy (3D-CRT) combined with transcatheter hepatic arterial chemoembolization (TACE) for patients with advanced hepatocellular carcinoma. Methods:　A total of 110 patients with hepatocellular carcinoma were randomized into TACE combined with hypofractionated 3D-CRT(HFR) and with conventional fractionated 3DCRT(CFR) and treated with TACE in 4 weeks. 3D-CRT was delivered in 48 to 64 Gy at 6 to 8 Gy per frations for HRF or once-daily frations of 1.8 to 2 Gy to 60 to 70 Gy for CFR. Results: Patients in the HFR arm achieved similar trends appeared in overall response rate, radiation fever, nausea, vomiting, myelosuppression with those in the CFR arm. The 1- , 2- , and 3-year survival rates were 78.2%, 50.9% and 25.9% for the HFR arm and 65.5%, 32.7% and 15% for the HFR arm, respectively (p=0.042).The median overall survival duration was 27 months for the HFR arm and 18 months for the HFR arm, respectively. Conclusion:　HFR arm achieved better 1-, 2-, and 3-year survival rates than HFR arm and it allowed a total dose of 48 to54 Gy at 6 to 8 Gy per frations to be safely administered to patients with inoperable advanced hepatocellular carcinoma.

　　【关键词】肝肿瘤/放射疗法；放射疗法,适形；化学栓塞，治疗性

　　[Key words] Liver neoplasma/ radiotherapy; Radiotherapy, conformal; Chemoembolization, therapeutic

　　在全世界，肝细胞癌占肿瘤致死原因的第四位和肿瘤发病率的第八位。肝癌首选外科切除，但是，约80%的患者在确诊时已失去手术的机会。对于不能手术切除的病变，预后不佳。近年来，三维适形放射治疗(3D-CRT)联合肝动脉化疗栓塞术（TACE）成为非手术肝癌的主要治疗方法[1-3]。

　　采用何种分割治疗方式正确进行肝癌的放射治疗，取决于肿瘤增值状态，其中α/β值是重要的参数，以及正常肝脏组织的耐受。然而，目前在体肝癌细胞的α/β值、肿瘤细胞增值状况尚不清楚，正常组织并发症概率数学模型的参数也不能给出满意的答案。因此，我们进行了低分割3D-CRT联合TACE治疗原发性肝癌的前瞻性临床研究，探索其有效性和治疗相关毒性，为正确的临床治疗提供依据。

　　1 材料和方法

　　1.1 病例选择

　　2001年10月到2007年5月共有110例患者入组本研究，其中82例男性，28例女性，平均年龄为46岁（30-73岁）。入选病例标准为：①根据UICC分期标准(2002年)，患者为影像学、组织学证明的原发性肝细胞癌；②KPS评分≥70分；③无肝脏放射史；④转氨酶的水平小于正常值上限的两倍；⑤血清总胆红素水平5cm               37                  30

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