Pahwa Prabhjyoti, Sharma Deepti, Yadav Pushpa, Thomas Sherin S, Hora Sandhya, Preedia Babu E, Ramakrishna Gayatri, Sarin Shiv K, Trehanpati Nirupama
Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India.
Department of Radiation Oncology, Institute of Liver and Biliary Sciences, New Delhi, India.
J Clin Exp Hepatol. 2025 Mar-Apr;15(2):102444. doi: 10.1016/j.jceh.2024.102444. Epub 2024 Oct 25.
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.
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.
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 ( = 0.028) and VEGF-A ( = 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 ( = 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 ( = 0.326) in patients in whom HGF was reduced post-SBRT.
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.
背景/目的：立体定向体部放射治疗（SBRT）已发展成为无法接受其他局部治疗的晚期肝细胞癌（HCC）患者的一种治疗选择。通过影像学检查、血清甲胎蛋白（AFP）以及维生素K缺乏诱导蛋白-II（PIVKA-II）水平评估治疗后的反应。尽管AFP和PIVKA-II具有良好的特异性，但二者的敏感性均为低到中等。本研究旨在寻找对患者生存结局有影响的更有效的生物标志物。
我们前瞻性地收集了18例接受SBRT患者的血样。在SBRT前、SBRT后第5天和第30天动态分析血清肝细胞生长因子（HGF）和血管内皮生长因子-A（VEGF-A）水平。记录局部控制（LC）、总生存期（OS）、无进展生存期（PFS）以及治疗后不良事件。
该队列的中位随访时间为12.5个月（范围4 - 30个月）。在整个队列中，估计的平均总生存期为21.2个月（95%置信区间[CI]，15.9 - 26.4），中位无进展生存期（mPFS）为8个月（95%CI，1.7 - 14.2）。PIVKA-II水平较高（SBRT前后）的患者VEGF-A和HGF浓度也升高。与无转移组相比，初诊时伴有转移的患者HGF（P = 0.028）和VEGF-A（P = 0.027）浓度更高。与第5天相比，SBRT后第30天VEGF-A和HGF水平升高的患者无进展生存期较差。实际上，SBRT后第30天与第5天相比VEGF-A水平较低的患者，其mPFS为22个月对6个月（P = 0.301）。同样，HGF升高的患者mPFS为6个月，而SBRT后HGF降低的患者mPFS为22个月（P = 0.326）。
我们得出结论，除PIVKA-II外，HGF和VEGF-A可作为SBRT后疾病早期进展的预后和预测标志物。然而，未来有必要进行进一步的前瞻性试验以验证结果。
