Lee Hyung Soon, Choi Gi Hong, Choi Jin Sub, Kim Kyung Sik, Han Kwang-Hyub, Seong Jinsil, Ahn Sang Hoon, Kim Do Young, Park Jun Yong, Kim Seung Up, Kim Beom Kyung
Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
Ann Surg Oncol. 2014 Oct;21(11):3646-53. doi: 10.1245/s10434-014-3652-3. Epub 2014 Jun 11.
This study evaluated the down-staging efficacy and impact on resectability of concurrent chemoradiotherapy (CCRT) followed by hepatic arterial infusion chemotherapy (HAIC) in locally advanced hepatocellular carcinoma, and identified prognostic factors of disease-free survival (DFS) and overall survival (OS) after curative resection.
DFS and OS were investigated using clinicopathologic variables. Functional residual liver volume (FRLV) was assessed before CCRT and again before surgery in patients with major hepatectomy. Tumor marker response was defined as elevated tumor marker levels at diagnosis but levels below cutoff values before surgery (α-fetoprotein < 20 ng/mL, protein induced by vitamin K absence or antagonist-II < 40 mAU/mL).
Of 243 patients who received CCRT followed by HAIC between 2005 and 2011, 41 (16.9 %) underwent curative resection. Tumor down-staging was demonstrated in 32 (78 %) of the resected patients. FRLV significantly increased from 47.5 to 69.9 % before surgery in patients who underwent major hepatectomy. In addition, the OS of the curative resection group was significantly higher than the OS of the CCRT followed by HAIC alone group (49.6 vs. 9.8 % at 5-year survival; p < 0.001). By multivariate analysis, the poor prognostic factors for DFS after curative resection were tumor marker non-response and the presence of a satellite nodule; however, tumor marker non-response was the only independent poor prognostic factor of OS.
CCRT followed by HAIC increased resectability by down-staging tumors and increasing FRLV. Curative resection may provide good long-term survival in tumor marker responders who undergo CCRT followed by HAIC.
本研究评估了同步放化疗（CCRT）联合肝动脉灌注化疗（HAIC）对局部晚期肝细胞癌降期的疗效及其对可切除性的影响，并确定了根治性切除术后无病生存期（DFS）和总生存期（OS）的预后因素。
采用临床病理变量研究DFS和OS。对接受大范围肝切除术的患者，在CCRT前及手术前再次评估功能性残余肝体积（FRLV）。肿瘤标志物反应定义为诊断时肿瘤标志物水平升高，但手术前低于临界值（甲胎蛋白<20 ng/mL，维生素K缺乏或拮抗剂-II诱导蛋白<40 mAU/mL）。
2005年至2011年间，243例接受CCRT联合HAIC治疗的患者中，41例（16.9%）接受了根治性切除。32例（78%）切除患者实现了肿瘤降期。接受大范围肝切除术的患者术前FRLV从47.5%显著增加到69.9%。此外，根治性切除组的OS显著高于单纯CCRT联合HAIC组（5年生存率分别为49.6%和9.8%；p<0.001）。多因素分析显示，根治性切除术后DFS的不良预后因素为肿瘤标志物无反应和存在卫星结节；然而，肿瘤标志物无反应是OS唯一独立的不良预后因素。
CCRT联合HAIC通过使肿瘤降期和增加FRLV提高了可切除性。根治性切除可能为接受CCRT联合HAIC治疗且肿瘤标志物有反应的患者提供良好的长期生存。
