Wang Hongyu, Li Bin, Wang Yu, Zhang Jiang, Wu Yanqin, Fan Wenzhe, Li Jiaping
Department of Interventional Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Clinical Trials Unit, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
J Cancer Res Ther. 2020;16(2):301-308. doi: 10.4103/jcrt.JCRT_898_19.
The aim of the study was to determine whether the time to progression (TTP) or time to untreatable progression (TTUP) is an appropriate surrogate endpoint for overall survival (OS) in patients with hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE).
Eighty-four patients with Barcelona clinic liver cancer (BCLC) stage B or C HCC underwent TACE. The correlations of TTP and TTUP with OS were evaluated after a log transformation of the indicated values. After identifying independent prognostic factors of TTP, TTUP, and OS, the partial correlations of TTP and TTUP with OS were analyzed in all patients and subgroups. Subsequently, the prognostic value of TTP and TTUP was compared by the multivariate survival analysis of OS.
Both the BCLC stage and tumor number were correlated with TTP and TTUP. In addition, the BCLC stage, initial treatment failure, and sorafenib administration were associated with OS. In all patients, the correlation coefficients of TTP and TTUP with OS were 0.559 and 0.789, respectively. Adjustment for independent prognostic factors yielded partial correlation coefficients which were 0.433 and 0.697, respectively. Furthermore, OS was found to be associated with TTUP (P = 0.003; hazard ratio: 0.253; 95% confidence interval: 0.10-0.63) but not with TTP.
Untreatable progression is more representative of clinical progression in patients with HCC who underwent TACE. In the current study, TTUP is a more appropriate surrogate endpoint for OS than TTP. Future studies should explore whether untreatable progression is a valuable endpoint event in clinical trials or an indicator of the need for second-line therapy.
本研究旨在确定进展时间（TTP）或不可治疗进展时间（TTUP）是否是经动脉化疗栓塞术（TACE）后肝细胞癌（HCC）患者总生存期（OS）的合适替代终点。
84例巴塞罗那临床肝癌（BCLC）分期为B或C期的HCC患者接受了TACE治疗。对所示值进行对数转换后，评估TTP和TTUP与OS的相关性。在确定TTP、TTUP和OS的独立预后因素后，分析所有患者及亚组中TTP和TTUP与OS的偏相关性。随后，通过OS的多因素生存分析比较TTP和TTUP的预后价值。
BCLC分期和肿瘤数量均与TTP和TTUP相关。此外，BCLC分期、初始治疗失败和索拉非尼的使用与OS相关。在所有患者中，TTP和TTUP与OS的相关系数分别为0.559和0.789。对独立预后因素进行调整后，偏相关系数分别为0.433和0.697。此外，发现OS与TTUP相关（P = 0.003；风险比：0.253；95%置信区间：0.10 - 0.63），但与TTP无关。
不可治疗进展更能代表接受TACE治疗的HCC患者的临床进展。在本研究中，TTUP是比TTP更合适的OS替代终点。未来的研究应探讨不可治疗进展是否是临床试验中有价值的终点事件或二线治疗需求的指标。
