Prognostic Role of Serum Vascular Endothelial Growth Factor and Hepatocyte Growth Factor Post Stereotactic Body Radiation in Advanced Hepatocellular Carcinoma

Abstract

Background/aims: Stereotactic body radiation therapy (SBRT) has evolved as a treatment alternative for advanced hepatocellular carcinoma (HCC) patients who are ineligible for other local therapies. Posttreatment responses are assessed by imaging modalities, serum AFP, and protein induced by vitamin K absence-II (PIVKA) II levels. Despite good specificity, both AFP and PIVKA-II have low to medium sensitivity. The study aimed to find more effective biomarkers that have an impact on the survival outcomes of the patients.

Methods: We have prospectively collected blood samples from 18 patients undergoing SBRT. Serum levels of hepatocyte growth factor (HGF) and vascular endothelial growth factor-A (VEGF-A) were analyzed kinetically pre-SBRT following day 5 and day 30 post-SBRT. Local control (LC), overall survival (OS), progression free survival (PFS), and postprocedure adverse events were recorded.

Results: The cohort had a median follow-up duration of 12.5 months (range 4-30 months). In the entire cohort, the estimated mean OS was 21.2 months (95% confidence interval [CI], 15.9-26.4), and the median progression free survival (mPFS) was 8 months (95% CI, 1.7-14.2). Patients with higher PIVKA-II levels (pre- and post-SBRT) also showed increased concentrations of VEGF-A and HGF. Patients with metastasis at presentation had higher HGF (P = 0.028) and VEGF-A (P = 0.027) concentrations compared to the nonmetastatic group. Patients with increased levels of VEGF-A and HGF at day 30 post-SBRT compared to day 5 had poor PFS. Indeed, the mPFS was 22 months vs 6 months (P = 0.301) in patients with low VEGF-A post SBRT on day 30 compared to day 5. Similarly, mPFS in patients with increase in HGF was 6 months as compared to 22 months (P = 0.326) in patients in whom HGF was reduced post-SBRT.

Conclusion: We conclude that in addition to PIVKA-II, HGF, and VEGF-A can be used as prognostic and predictive markers for early progression of disease post-SBRT. However, further prospective trials are warranted in the future to validate the results.

Keywords: hepatocellular carcinoma; hepatocyte growth factor; prognosis; stereotactic body radiation therapy; vascular endothelial growth factor-A.