Shim Ju Hyun, Park Joong-Won, Kim Ji Hoon, An Min, Kong Sun-Young, Nam Byung-Ho, Choi Joon-Il, Kim Hyun Beom, Lee Woo Jin, Kim Chang-Min
Center for Liver Cancer, Natinoal Cancer Center, Ilsan-Gu, Goyang, Gyeonggi, Republic of Korea.
Cancer Sci. 2008 Oct;99(10):2037-44. doi: 10.1111/j.1349-7006.2008.00909.x.
We prospectively investigated the association between a change of serum vascular endothelial growth factor (VEGF) level after transcatheter arterial chemoembolization (TACE) and hepatocellular carcinoma (HCC) patient prognosis. The study involved 147 patients with unresectable HCC treated at the National Cancer Center, Korea, between July and December 2005. Serum samples were collected from each patient before TACE, and 1-2 days and 1 month after TACE. Serum VEGF concentrations were measured using an enzyme-linked immunosorbent assay (ELISA). The log(e)(VEGF/platelets) increased transiently 1-2 days after TACE and declined thereafter. Frequency of previous TACE did not correlate with log(e)(VEGF/platelets). This study found that log(e)(VEGF/platelets) 1-2 days after TACE, but not log(e)(VEGF/platelets) at baseline, was strongly correlated with vascular or nodal invasion and AJCC (American Joint Committee on Cancer)/UICC (International Union Against Cancer) stage, and was significantly greater in men. Relative changes in serum VEGF/platelet levels 1-2 days after TACE (DeltaVEGF) > 0.5 were directly correlated with tumor size, vascular invasion and modified UICC and AJCC/UICC stage (P < 0.05 for each). Additionally, DeltaVEGF > 0.5 was significantly correlated with newly developed extrahepatic metastases one and six months after TACE (P = 0.005 and 0.003, respectively). Progression free survival of patients with DeltaVEGF > 0.5 was significantly worse (P < 0.001) and DeltaVEGF > 0.5 was an independent prognostic factor for PFS (hazard ratio, 3.111; P < 0.001). This study showed that a high increment in serum VEGF level 1-2 days after TACE in HCC patients was associated with distant metastasis and unfavorable outcomes.
我们前瞻性地研究了经动脉化疗栓塞术(TACE)后血清血管内皮生长因子(VEGF)水平的变化与肝细胞癌(HCC)患者预后之间的关联。该研究纳入了2005年7月至12月在韩国国立癌症中心接受治疗的147例不可切除HCC患者。在TACE前、TACE后1 - 2天和1个月分别采集每位患者的血清样本。采用酶联免疫吸附测定(ELISA)法检测血清VEGF浓度。TACE后1 - 2天,log(e)(VEGF/血小板)短暂升高,随后下降。既往TACE的次数与log(e)(VEGF/血小板)无关。本研究发现,TACE后1 - 2天的log(e)(VEGF/血小板),而非基线时的log(e)(VEGF/血小板),与血管或淋巴结侵犯以及美国癌症联合委员会(AJCC)/国际抗癌联盟(UICC)分期密切相关,且男性患者该指标显著更高。TACE后1 - 2天血清VEGF/血小板水平的相对变化(DeltaVEGF)> 0.5与肿瘤大小、血管侵犯以及改良的UICC和AJCC/UICC分期直接相关(每项P < 0.05)。此外,DeltaVEGF > 0.5与TACE后1个月和6个月新出现的肝外转移显著相关(分别为P = 0.005和0.003)。DeltaVEGF > 0.5的患者无进展生存期显著更差(P < 0.001),且DeltaVEGF > 0.5是无进展生存期的独立预后因素(风险比,3.111;P < 0.001)。本研究表明,HCC患者TACE后1 - 2天血清VEGF水平的大幅升高与远处转移及不良预后相关。