晚期肝癌患者手術後經Sorafenib治療之預後

肝細胞癌（Hepatocellular carcinoma, HCC）是世界第五大最常見的癌症，也是全球第三大因癌症導致死亡的主要原因。Sorafenib（Nexavar，蕾莎瓦）於2007年核准用於治療晚期肝癌的標靶藥物，也是晚期肝癌的首要推薦治療選擇。研究已知Sorafenib對於腫瘤反應效果比較差，但是在總存活期OS（overall survival）是有其效益。近年來也證實晚期肝癌使用Sorafenib合併動脈導管肝腫瘤化學栓塞術（Transcatheter Arterial Chemoembolization, TACE）顯示出有更好的OS。此外多篇研究皆說明多重合併治療能有效延長晚期肝癌的總存活期。本篇研究將利用回溯性研究，篩選出同為晚期肝癌患者裡，分析未經手術治療過與曾手術治療後而腫瘤復發的兩個族群，在服用Sorafenib的預後分析之相關性。收集中部某區域教學綜合醫院服用Sorafenib的肝癌患者（2012至2019；1710例），經篩選出研究母群體共147例。再經傾向分數比對（Propensity score matching method）進行1：1配對，未經手術的晚期肝癌患者（No Surgery experience, 38例）；經手術後腫瘤復發的晚期肝癌患者（Surgery experience,38例）。總存活期（Overall Survival, OS）及疾病無惡化存活期（Progression Free Survival, PFS）為本研究的最終評估治療效果。研究結果顯示經手術後腫瘤復發的晚期肝癌患者與未經手術的晚期肝癌患者的中位存活期（Median Overall survival）446 V.S 150 days, Hazards Ratio 0.44（95% CI 0.27–0.73，P=0.001）及中位疾病無惡化存活期（Median progression free survival）134 V.S 56 days, Hazards Ratio 0.56（95% CI 0.37–0.94，P=0.003）。曾手術治療過的晚期肝癌患者服用Sorafenib治療與同為晚期肝癌患者卻未曾手術治療過相比，仍舊顯著的改善存活期及疾病無惡化存活期。經過本研究說明手術可以讓中晚期肝癌患者的腫瘤負擔降低，以達到較好的預後，往後即便腫瘤再復發或進展成晚期肝癌，再服用Sorafenib的治療仍比未手術治療過的患者具有更好的預後。因此，經本研究得知中晚期肝癌患者的治療建議手術治療為主，且手術治療後的益處甚至讓復發後的晚期肝癌患者也獲得較好存活期。

Hepatocellular carcinoma (HCC) is the fifth most commonly diagnosed cancer and the third leading cause of cancer death world-wide. Sorafenib was the first systemic drug approved in 2007 for the treatment of hepatocellular carcinoma and standard of care for frontline therapy. Clinical studies demonstrated some benefits of sorafenib on overall survival (OS), its efficacy against for tumor response remains moderate. In recent years, the combination therapy of transcatheter arterial chemoembolization (TACE) plus sorafenib has been increasingly used in patients with advanced HCC. Patients with advanced HCC patients who received sorafenib in a reginal teaching Hospital, between January 2012 and December 2019 were retrospectively enrolled in this study. We evaluated their clinical outcomes of those with surgery experience and without surgery experience. Among 147 patients who were eligible for the analysis and through propensity score matching, we divided patients into the No surgery experience arm (n = 38) and Surgery experience arm (n = 38; patients received sorafenib for advanced recurrence HCC). The primary endpoint was overall survival (OS) and progression free survival (PFS). The Surgery experience arm had significantly improved the median overall survival was 446 vs. 150 days (hazard ratio 0.44; 95% confidence interval 0.27–0.73，P = 0.001) and median progression free survival 134 vs. 56 days (hazard ratio 0.56; 95% confidence interval 0.37–0.94，P=0.003). The median OS and PFS were significantly longer in the Surgery experience arm than in the No surgery experience arm. We conclude that debulking the intrahepatic tumor burden is prolong survival time of patients with intermediate and advanced-stage HCC. Therefore, liver resection the first choice in the treatment of patients with intermediate and advanced-stage HCC. The benefits of surgical treatment even enable patients with advanced recurrence HCCs to achieve better survival.