Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
BMC Med. 2022 Oct 31;20(1):415. doi: 10.1186/s12916-022-02608-6.
Hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin and 5-fluorouracil was effective in unresectable hepatocellular carcinoma (HCC). The program of FOLFOX-HAIC in HCC was performed for 1 day (HAIC 1d) or 2 days (HAIC 2d). We hereby retrospectively compared the efficacy and safety between these two treatment regimens and explored the predictive power of thymidylate synthase (TYMS), an enzyme involved in the DNA synthesis process and metabolism of fluorouracil.
This study included patients with a primary diagnosis of unresectable HCC. These patients received HAIC for 1 day or 2 days. The overall survival (OS), progression-free survival (PFS), tumor response, and adverse events were compared. The propensity score matching (PSM) was used to reduce bias. Peripheral blood samples before the treatments were collected and used to measure the concentration of TYMS through enzyme-linked immunosorbent assay (ELISA). ELISA was performed according to the manufacturers' guidelines.
We included 368 patients for this study: 248 in the HAIC 1d group and 120 in the HAIC 2d group. There was no significant difference of OS between the two groups (14.5 for HAIC 1d vs 15.3 months for HAIC 2d, p=0.46). Compared with the HAIC 1d group, the HAIC 2d group did not prolong the PFS (7.3 vs 7.5 months, p=0.91) or elevate the tumor response (42.5% vs 39.1%, p=0.53) per RECIST 1.1. In the PSM cohort, the efficacy between the two groups was similar. The total frequencies of grade 3-4 events were higher with the HAIC 2d group than with the HAIC 1d group, especially in the PSM cohort (p=0.043). Additionally, patients with TYMS low level might benefit longer OS from the HAIC 2d group (18.7 vs 13.6 months, p=0.014).
There was not much of a difference in efficacy between the two groups, but the HAIC for 1 day might be safer, which needed further research. The level of TYMS might be the predictive biomarkers.
奥沙利铂联合氟尿嘧啶的肝动脉灌注化疗（HAIC）对不可切除的肝细胞癌（HCC）有效。FOLFOX-HAIC 方案在 HCC 中的应用时间为 1 天（HAIC 1d）或 2 天（HAIC 2d）。我们在此回顾性比较了这两种治疗方案的疗效和安全性，并探讨了胸苷酸合成酶（TYMS）的预测能力，TYMS 是一种参与 DNA 合成过程和氟尿嘧啶代谢的酶。
本研究纳入了原发性不可切除 HCC 患者。这些患者接受 HAIC 治疗 1 天或 2 天。比较总生存期（OS）、无进展生存期（PFS）、肿瘤反应和不良事件。采用倾向评分匹配（PSM）减少偏倚。在治疗前采集外周血样，通过酶联免疫吸附试验（ELISA）测量 TYMS 浓度。ELISA 按照制造商的指南进行。
本研究纳入了 368 例患者：HAIC 1d 组 248 例，HAIC 2d 组 120 例。两组 OS 无显著差异（HAIC 1d 组为 14.5 个月，HAIC 2d 组为 15.3 个月，p=0.46）。与 HAIC 1d 组相比，HAIC 2d 组并未延长 PFS（RECIST 1.1 标准下分别为 7.3 个月和 7.5 个月，p=0.91）或提高肿瘤反应率（分别为 42.5%和 39.1%，p=0.53）。在 PSM 队列中，两组的疗效相似。HAIC 2d 组 3-4 级不良事件总发生率高于 HAIC 1d 组，尤其是在 PSM 队列中（p=0.043）。此外，TYMS 水平较低的患者可能从 HAIC 2d 组获得更长的 OS（18.7 个月 vs 13.6 个月，p=0.014）。
两组疗效差异不大，但 HAIC 1 天可能更安全，这需要进一步研究。TYMS 水平可能是预测生物标志物。
