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经导管动脉化疗栓塞术治疗后肝细胞癌患者预后和索拉非尼相关生存获益的潜在预测因子的鉴定。

Identification of Potential Predictors of Prognosis and Sorafenib-Associated Survival Benefits in Patients with Hepatocellular Carcinoma after Transcatheter Arterial Chemoembolization.

机构信息

Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.

出版信息

Curr Oncol. 2022 Dec 29;30(1):476-491. doi: 10.3390/curroncol30010038.

Abstract

Some studies have shown that sorafenib could significantly prolong the overall survival of patients with unresectable hepatocellular carcinoma treated with transcatheter arterial chemoembolization (TACE). However, other studies revealed that patients had no access to sorafenib-related survival benefits after TACE. To identify the predictive biomarkers of therapeutic efficacy of sorafenib, we explored the potential predictive value of vascular endothelial growth factor (VEGF) and other clinical variables for survival benefits from sorafenib in patients treated with TACE previously. The results demonstrated that patients with tumor size > 7 cm or total bilirubin ≤ 17.3 μmol/L showed significant survival benefits from sorafenib after TACE treatment compared with those with tumor size ≤ 7 cm or total bilirubin > 17.3 μmol/L. Meanwhile, patients with VEGF > 131.09 pg/mL may obtain sorafenib-associated survival benefits after TACE when compared to those with VEGF ≤ 131.09 pg/mL, which needs further confirmation. The abovementioned results are helpful to confirm the specific population who are sensitive to targeted therapy. (1) Background: VEGF plays a crucial role in modulating proliferation and metastasis in HCC. We aimed to explore the relationship between VEGF and the prognosis, as well as the mortality risk of HCC patients who received TACE, and whether it and other variables could be considered as potential biomarkers for predicting the benefits from sorafenib. (2) Method: A total of 230 consecutive newly diagnosed patients with unresectable HCC treated with either TACE or TACE−sorafenib were collected retrospectively. Cox regression analyses were performed to evaluate the prognostic value of VEGF. Furthermore, restricted cubic splines were fitted to assess the nonlinear associations between VEGF and OS, and the threshold effect analysis was subsequently performed. Lastly, the potential factors for predicting the survival benefits from sorafenib after the TACE procedure were identified using the Cox proportional hazard model with an interaction term. (3) Results: VEGF was recognized as an independent prognostic factor for OS in the TACE alone cohort (HR = 3.237, p = 0.013). A nonlinear relationship was observed between VEGF and OS in HCC patients with TACE administration after adjustment for confounders (p for nonlinearity = 0.030); the mortality risk increased with increasing the baseline VEGF before the inflection point, and the HR for death was 1.008. There was no significant interaction between the VEGF levels and treatment modality (p for interaction = 0.233), and further studies are needed to identify its predictive value on the efficacy of sorafenib. Patients with tumor size > 7 cm or total bilirubin ≤ 17.3 μmol/L derived significant sorafenib-related benefits in OS when compared to those with tumor size ≤ 7 cm or total bilirubin > 17.3 μmol/L (p for interaction = 0.004 and 0.031, respectively). (4) Conclusions: Within a certain concentration range, elevated baseline VEGF meant an increased risk of death in HCC patients treated with TACE. Significant improvements in OS associated with sorafenib were observed in patients with higher tumor size and lower total bilirubin after TACE treatment.

摘要

一些研究表明,索拉非尼可显著延长接受经导管动脉化疗栓塞 (TACE) 治疗的不可切除肝细胞癌患者的总生存期。然而,其他研究表明,TACE 后患者无法获得与索拉非尼相关的生存获益。为了确定索拉非尼治疗疗效的预测生物标志物,我们探索了血管内皮生长因子 (VEGF) 和其他临床变量对先前接受 TACE 治疗的患者接受索拉非尼治疗后生存获益的潜在预测价值。结果表明,与肿瘤大小≤7cm 或总胆红素>17.3μmol/L 的患者相比,肿瘤大小>7cm 或总胆红素≤17.3μmol/L 的患者在接受 TACE 治疗后从索拉非尼治疗中获得了显著的生存获益。同时,与 VEGF≤131.09pg/mL 的患者相比,VEGF>131.09pg/mL 的患者在接受 TACE 后可能获得与索拉非尼相关的生存获益,但需要进一步确认。上述结果有助于确认对靶向治疗敏感的特定人群。

(1)背景:VEGF 在调节 HCC 的增殖和转移中起着关键作用。我们旨在探讨 VEGF 与 TACE 治疗的 HCC 患者的预后和死亡率之间的关系,以及它和其他变量是否可以被认为是预测索拉非尼获益的潜在生物标志物。

(2)方法:回顾性收集了 230 例新诊断为不可切除 HCC 且接受 TACE 或 TACE-索拉非尼治疗的连续患者。使用 Cox 回归分析评估 VEGF 的预后价值。此外,拟合受限立方样条来评估 VEGF 与 OS 之间的非线性关系,并随后进行阈值效应分析。最后,使用具有交互项的 Cox 比例风险模型确定预测 TACE 术后索拉非尼生存获益的潜在因素。

(3)结果:VEGF 被认为是 TACE 单药治疗队列中 OS 的独立预后因素(HR=3.237,p=0.013)。在调整混杂因素后,观察到 VEGF 与 HCC 患者接受 TACE 治疗后的 OS 之间存在非线性关系(p 非线性=0.030);在拐点前,基线 VEGF 越高,死亡风险越高,死亡的 HR 为 1.008。VEGF 水平与治疗方式之间无显著交互作用(p 交互=0.233),需要进一步研究以确定其对索拉非尼疗效的预测价值。与肿瘤大小≤7cm 或总胆红素>17.3μmol/L 的患者相比,肿瘤大小>7cm 或总胆红素≤17.3μmol/L 的患者在 OS 方面从索拉非尼治疗中获得了显著的相关获益(p 交互=0.004 和 0.031)。

(4)结论:在一定浓度范围内,升高的基线 VEGF 意味着接受 TACE 治疗的 HCC 患者死亡风险增加。在接受 TACE 治疗后,肿瘤较大且总胆红素较低的患者,与索拉非尼相关的 OS 显著改善。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2890/9857819/9dc20fb0dbf8/curroncol-30-00038-g001.jpg

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