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FACTORS ASSOCIATED WITH RADIOGRAPHIC RESPONSE AND OVERALL SURVIVAL AFTER STEREOTACTIC ABLATIVE RADIOTHERAPY FOR HEPATOCELLULAR CARCINOMA WITH PORTAL VEIN TUMOR THROMBOSIS

肝癌合併門靜脈腫瘤栓塞以立體定位消融放射治療之臨床結果及預後因子分析

摘要


Introduction : Survival of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) is poor. While stereotactic ablative radiotherapy (SABR) has emerged as a treatment option for HCC, there are limited data on treatment outcomes and associated prognostic factors focusing on PVTT patients. Methods and Materials : Between 2008 and 2013, 42 HCC patients with PVTT underwent SABR using a Cyberknife radiosurgery system in our institute. The mean radiation dose was 42.5 Gy, 5–12.5 Gy per fraction. We collected clinical and treatment-related factors including age, Eastern Cooperative Oncology Group (ECOG) performance status, α-fetoprotein (AFP) level, Child-Pugh score, Cancer of the Liver Italian Program (CLIP) score, presence of extrahepatic metastasis (EM), and equivalent dose in 2 Gy fractions (EQD2). The patients were assessed for radiographic response and survival outcome. Image response was evaluated with Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Overall survival (OS) was calculated using the Kaplan-Meier test. Prognostic factors were evaluated using a Cox regression model. Results : At the last follow up, 38 patients had died. The median survival was 8.6 months, with 1-year and 2-year OS rates of 31.4% and 14.1%, respectively. Nine patients died before imaging studies for response evaluation could be performed. In those who had radiographic response evaluation, 3% had a complete response, 55% a partial response, 39% stable disease, and 3% disease progression. Nine (21%) patients had portal vein re-canalization and then received transarterial chemoembolization (TACE). In univariate analysis, Child-Pugh A (vs. B & C, HR = 0.470, p = 0.049), CLIP score ≤ 3 (vs. > 3, HR = 0.468, p = 0.046), and absence of EM (vs. presence of EM, HR = 0.497, p = 0.035) were associated with a higher OS rate. Multivariate analysis showed that only an absence of EM (vs. presence of EM, HR = 0.340, p = 0.015) was a significant prognostic indicator. Conclusions : SABR is an option for HCC patients with PVTT. Absence of EM is the only independent prognostic factor for better OS. A future large-scale study to identify strict patient selection criterion may maximize the benefits of SABR.

並列摘要


前言:肝癌病人如有合併門靜脈腫瘤栓塞存活率相當差。近年來許多證據支持立體定位消融放射治療可當作肝癌病人治療選擇,但是極少文獻報導關於肝癌合併門靜脈腫瘤栓塞使用立體定位消融放射治療之臨床結果及預後因子。材料與方法:本研究以回溯性的方式,篩選西元 2008 年至 2013 年於本部接受立體定位消融放射治療之 42 位肝癌合併門靜脈腫瘤栓塞病人,本部立體定位消融放射治療之執行是使用電腦刀影像導引立體放射手術系統(Cyberknife image-guided radiosurgery system (AccurayInc., Sunnyvale, CA))。所有病患接受之平均劑量為 42.5 Gy, 每次照射 5-12.5 Gy。臨床與治療相關的因子皆會詳細記錄,包括年齡、美國東岸癌症臨床研究合作組織(Eastern Cooperative Oncology Group)體能狀態、甲種胎兒蛋白數值、Child-Pugh score、Cancer of the Liver Italian Program (CLIP) score、有無肝外轉移(extrahepatic metastasis (EM))等等。治療後會依據追蹤的影像評估腫瘤反應,影像上腫瘤反應之評估是依據 Response Evaluation Criteria in Solid Tumors (RECIST) 此一準則。存活率的分析是使用 Kaplan-Meier 法。預後因子的分析則是使用 Cox 比例風險模式。結果:追蹤時間中位數為 7.8 個月,共有 38 名病患死亡,中位數存活期為 8.6 個月,第一年及第二年的整體存活率分別是 31.4%及 14.1%。9 名病患在還沒接受治療後第一次影像追蹤即死亡。在有接受任何一次治療後影像學評估的病患當中,腫瘤完全反應率(complete response)是 3%,部分反應率(partial response) 是 55%,疾病穩定率(stable disease)是 39.1%,而病情惡化率(disease progression)是 3%。9 名(21%)病患門靜脈有被打通且有接受後續肝動脈化學栓塞療法(transarterial chemoembolization)。單變量分析發現 Child-Pugh A (vs. B & C, HR = 0.470, p = 0.049)、CLIP score ≤ 3 (vs. > 3, HR = 0.468, p = 0.046) 以及無肝外轉移(vs. presence of EM, HR = 0.497, p = 0.035)的患者會有較佳的整體存活率。多變量分析則發現無肝外轉移(vs. presence of EM, HR = 0.340, p = 0.015)是唯一有統計學意義的預後因子。結論:立體定位消融放射治療,是肝癌合併門靜脈腫瘤栓塞病患的一個治療選擇;無肝外轉移是唯一可以預測較佳整體存活的獨立預後因子。

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