Three-dimentional conformal radiotherapy with or without oral Thalidomide for advanced hepatocellular carcinoma

三度空間順形放射治療合併口服「沙利竇邁」與否對肝細胞癌患者治療之評估

李明憲(Ming-Hsien Li) ； 劉育昌(Yu-chang Liu) ； 陳裕仁(Yu-Jen Chen) ； 李又文(Yu-Wen Li) ； 張國華(Kou-Hwa Chang)

《放射治療與腫瘤學》 14卷2期 (2007/06) Pp. 83-93

https://doi.org/10.6316/TRO/200714(2)83

摘要

目的：本篇研究對象為無法接受肝動脈化學栓塞、酒精注射或者經治療後復發的肝細胞癌患者，在其接受三度空間順形放射治療時，投予或不投予口服「沙利竇邁」，並比較治療效果是否有所差異。
材料及方法：自2001年1月至2004年10月間，共有37位於馬偕紀念醫院接受三度空間順形放射治療的肝細胞癌患者納入此次的回溯性研究。這些患者在1999年5月至2004年9月間被診斷為肝細胞癌。其中有6位患者因為晚期肝硬化（Child-Pugh class C）以及2位因為非腫瘤的肝臟部份小於40%而被排除在外。在這次統計的29位患者中，共有17（58.6%）位患者同時合併口服「沙利竇邁」（100-200 mg/day）。在放射治療技術方面，使用直線加速器6或10百萬伏特之光子射線，每天劑量為 160-180 cGy，總劑量為 39.6-50.4 Gy。統計並分析治療反應率、存活率以及其影響因子。
結果：在29位患者中，17位有明顯的腫瘤縮小反應；治療反應率為59%。根據統計結果，年紀（P = 0.022）與有無病毒性肝炎（P=0.026）對治療反應率有明顯的影響。這29位患者從診斷出肝細胞癌開始算起，第1、第2與第5年的存活率分別為 57.5%、29.0%與10.1%。從開始接受順行放射治療開始算起，第6、第12與第 18 個月的存活率分別為 50.4%、19.7% 與11.3%。根據單變項分析，血清中甲種胎兒蛋白（P=0.003）與肝硬化（P= 0.036）對於存活率有顯著的影響。但在多變項分析的模式下，只有血清中甲種胎兒蛋白（P = 0.01）仍對存活率有明顯的影響。
結論：三度空間順形放射治療對於無法接受肝動脈化學栓塞、酒精注射或者經治療後復發的肝細胞癌患者有中等程度的腫瘤控制效果。就短期生存率而言，合併口服「沙利竇邁」可能有改善。但是否可以增加患者的生活品質仍然需要更進一步的研究。此外統計發現較高的血清中甲種胎兒蛋白（尤其大於 4000 IU/ml）有明顯較差的生存率。我們仍需更進一步、更嚴謹的研究來確認三度空間順形放射治療合併口服「沙利竇邁」的效果。

並列摘要

Purpose : To compare the efficacy and long-term survival rates between the treatments of three-dimensional conformal radiotherapy (3D-CRT) combined with and without thalidomide for advanced hepatocellular carcinoma (HCC) patients for whom
transarterial embolization (TAE) or percutaneous ethanol injection therapy (PEIT) was ineffective or unsuitable.
Materials and Methods : From January 2001 to October 2004, 37 advanced HCC patients who received 3D-CRT at Mackay Memorial Hospital, Taipei, Taiwan were enrolled in this retrospective study. They were diagnosed as HCC during May 1999 to September 2004. Six patients with Child–Pugh class C and 2 patients with nontumor part of liver below 40% were excluded from this study. Seventeen (58.6%) of 29 patients were given thalidomide (100-200 mg/day) concomitantly with 3D-CRT. All treatments were delivered by means of a linear accelerator using 6 or 10 MV photons.
Radiotherapy was given 5 days a week with fraction dose of 1.6-1.8 Gy per day. The radiation dose to the target volume ranged from 39.6 to 50.4 Gy (46.8±5.1 Gy). Treatment response, survival rates and factors affecting survival were analyzed.
Results : Primary tumor responses were observed in 17 (59%) patients. Age (P = 0.022) and viral hepatitis (P = 0.026) significantly influenced the tumor response.
Overall survival rates form the time of diagnosis of 29 patients at 1, 2 and 5 years were 57.5%, 29.0% and 10.1%, respectively. From the time of starting 3D-CRT, survival rates at 6, 12 and 18 months were 50.4%, 19.7% and 11.3%, respectively. The 1-year survival rate was 26.9% and 7.1% in the combined modality group and 3D-CRT alone group, respectively. On univariate analysis, both alpha-fetoprotein (AFP) level (P = 0.003) and liver cirrhosis (P =0.036) were shown to significantly affect survival. On multivariate analysis, only AFP level (P = 0.001) was shown to significantly affect survival.
Conclusion : 3D-CRT provides a moderate tumor control in hepatoma patients who failed or were unsuitable for TAE/PEIT. Addition of oral thalidomide may have a benefit
on short-term survival rate, indicating that vascular disruptive agent could be an adjunct to radiotherapy. Whether this combination improves quality of life remains to be determined.
In addition, higher serum AFP level, especially over 4000 IU/ml, had a signifi-cantly poor survival rate. Further randomized-controlled study is mandatory to identify the efficacy of 3D-CRT combined with thalidomide.