Purpose High serum vascular endothelial growth factor (VEGF) levels have been identified as an independent risk factor for hepatocellular carcinoma (HCC). We aimed to construct a VEGF-included prognostic model to accurately perform individualized predictions of survival probability for patients with unresectable HCC. Patients and Methods From October 2018 to March 2021, 182 consecutive newly diagnosed patients with unresectable HCC were retrospectively enrolled. Baseline serum VEGF-A and other characteristics were collected for all patients. Univariate Cox regression analysis and LASSO regression model were applied to develop the prognostic model, enhanced bootstrap method with 100 replicates was performed to validate its discrimination and calibration. We compared the final model with China Liver Cancer (CNLC) stage, American Joint Committee on Cancer (AJCC) stage, Barcelona Clinic Liver Cancer (BCLC) stage, and the model without the “VEGF”. Finally, the established model was stratified by age. Results The VEGF-associated prognostic model we established has high accuracy with an overall C-index of 0.7892 after correction for optimistic estimates. The area under the curve (AUC) of the time-dependent receiver operating characteristic (ROC) curves at 6-month, 1-year, and 2-year after correction were 0.843, 0.860, 0.833, respectively, and the calibration of the model was 0.1153, 0.1514, and 0.1711, respectively. The final model showed significant improvement in predicting OS when compared to the other models according to Harrell’s C-index, The AUC of the time-dependent ROC, area under the decision curve analysis (AUDC), integrated discrimination improvement (IDI), and continuous net reclassification index (NRI). Conclusion The VEGF-associated prognostic model may help to predict the survival probabilities of HCC patients with favorable performance and discrimination. However, further validation is required since we only verified this model using internal but not external data.
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.
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