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

• Published in: Current oncology (Toronto) 2022-12, Vol.30 (1), p.476-491
• Main Authors: He, Kun, Yang, Zelong, Liu, Xinyu, Yang, Yanling, Song, Wenjie, Wang, Shangyu, Chen, Yong
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - therapeutic use; Carcinoma, Hepatocellular - drug therapy; Chemoembolization, Therapeutic - adverse effects; Chemoembolization, Therapeutic - methods; hepatocellular carcinoma; Humans; Liver Neoplasms - drug therapy; Niacinamide - adverse effects; Niacinamide - therapeutic use; Phenylurea Compounds - adverse effects; Phenylurea Compounds - therapeutic use; predictors; Prognosis; Retrospective Studies; sorafenib; Sorafenib - therapeutic use; transcatheter arterial chemoembolization; Treatment Outcome; vascular endothelial growth factor; Vascular Endothelial Growth Factor A - therapeutic use
• ISSN: 1718-7729; 1198-0052; 1718-7729
• DOI: 10.3390/curroncol30010038

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. Th