Pinato D J, Karamanakos G, Arizumi T, Adjogatse D, Kim Y W, Stebbing J, Kudo M, Jang J W, Sharma R
Division of Experimental Medicine, Imperial College London, Hammersmith Hospital, London, UK.
Aliment Pharmacol Ther. 2014 Dec;40(11-12):1270-81. doi: 10.1111/apt.12992. Epub 2014 Oct 18.
Transarterial chemoembolisation (TACE) is a standard treatment for unresectable, intermediate stage hepatocellular carcinoma (HCC). Survival after TACE, however, can be highly variable, with no suitable biomarker predicting therapeutic outcome. The inflammation-based index (IBI) has previously been shown to independently predict overall survival (OS) in all stages of HCC.
To explore the prognostic ability of IBI as a predictor of survival after TACE.
Baseline staging, biochemical and clinicopathological features including IBI were studied in a derivation set of 64 patients undergoing TACE for intermediate stage HCC. Dynamic changes in IBI before and after TACE were studied as predictors of survival using both a univariate and multivariate Cox regression model and further validated in two independent patient cohorts from Korea (n = 76) and Japan (n = 577).
Pre-treatment IBI predicted for OS in the derivation set (P = 0.001). Other univariate predictors of OS included radiological response to TACE (P < 0.001), pre-TACE CLIP score (P < 0.01), tumour diameter >5 cm (P = 0.05) and AFP ≥400 (P < 0.001). Normalisation of IBI post-TACE was associated with radiological response by mRECIST criteria and improved OS (P < 0.001). Normalisation of IBI remained a significant multivariate predictor of OS in both the derivation and validation sets (P < 0.001).
Normalisation of IBI after TACE is shown to be an independent predictor of survival and may be integrated into the retreatment criteria for repeat TACE in intermediate stage HCC. IBI and its dynamic changes after treatment are validated as a biomarker allowing the stratification of patients with a significant survival advantage following initial TACE.
经动脉化疗栓塞术(TACE)是不可切除的中期肝细胞癌(HCC)的标准治疗方法。然而,TACE后的生存期差异很大,尚无合适的生物标志物可预测治疗结果。基于炎症的指标(IBI)此前已被证明可独立预测HCC各阶段的总生存期(OS)。
探讨IBI作为TACE后生存期预测指标的预后能力。
在一组64例接受TACE治疗的中期HCC患者的衍生队列中,研究了包括IBI在内的基线分期、生化及临床病理特征。使用单变量和多变量Cox回归模型研究TACE前后IBI的动态变化作为生存期的预测指标,并在来自韩国(n = 76)和日本(n = 577)的两个独立患者队列中进一步验证。
治疗前IBI可预测衍生队列中的OS(P = 0.001)。OS的其他单变量预测指标包括对TACE的放射学反应(P < 0.001)、TACE前CLIP评分(P < 0.01)、肿瘤直径>5 cm(P = 0.05)和甲胎蛋白≥400(P < 0.001)。TACE后IBI的正常化与根据mRECIST标准的放射学反应相关,并改善了OS(P < 0.001)。在衍生队列和验证队列中,IBI的正常化仍然是OS的显著多变量预测指标(P < 0.001)。
TACE后IBI的正常化被证明是生存期的独立预测指标,可纳入中期HCC重复TACE的再治疗标准。IBI及其治疗后的动态变化被验证为一种生物标志物,可对初次TACE后具有显著生存优势的患者进行分层。