3536 - PIVKA-II as an Adjunct Biomarker to AFP for the Assessment of the Early Radiographic Treatment Response to SBRT in HCC
Presenter(s)
S. Sil1, K. M. Banson1, A. Singh2, J. Xiao3, D. B. Hewitt4, G. D. Sacks4, M. Silk5, C. Wolfgang4, K. L. Du6, A. Mahadevan1, and C. Hill1; 1Department of Radiation Oncology, NYU Langone Health, New York, NY, 2Department of Chemistry and Biochemistry, University of California–Los Angeles, Los Angeles, CA, 3Department of Radiation Oncology, NYU Grossman School of Medicine, New York, NY, 4Department of Hepatobiliary and Pancreatic Surgery, NYU Langone Health, New York, NY, 5Department of Vascular and Interventional Radiology, NYU Langone Health, New York, NY, 6Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT
Purpose/Objective(s): The radiographic assessment of treatment response to stereotactic body radiation (SBRT) in hepatocellular carcinoma (HCC) is often confounded by persistent arterial phase hyper-enhancement (APHE) and washout even in effectively treated HCC. Protein induced by vitamin K absence or antagonist II (PIVKA-II) may be a more specific biomarker for HCC than alpha fetoprotein (AFP) and has a shorter half-life. Higher PIVKA-II levels may correlate with larger tumor size, macrovascular invasion (MVI), and extrahepatic disease. We hypothesize that PIVKA-II is more reflective of tumor biology compared to AFP and post-SBRT kinetics may help assess the treatment response even with APHE.
Materials/Methods: This is a single institution retrospective study, including patients with HCC treated with SBRT from 2012-2024 with PIVKA-II levels pre-SBRT. The changes in AFP and PIVKA-II were calculated as the difference between the pre-SBRT level and the nadir within 1-6 months after SBRT and were only calculated for patients that had elevated AFP or PIVKA-II levels prior to SBRT.
Results: 15 patients with HCC were included with a median follow-up of 8 months. At diagnosis, the majority were Child-Pugh class A (60%) and albumin-bilirubin index grade 2 (67%). Multifocal disease was present in 13 patients (87%), 4 (27%) had MVI, and 0 had extrahepatic disease. The median tumor size was 4.65 cm (range 1.2-10.2 cm). The median SBRT dose delivered was 50 Gy in a median of 5 fractions. Median serum AFP and PIVKA-II pre-SBRT were 10.4 ng/ml (range 2.5-1525) and 12.2 ng/ml (range 0.2-206.2), respectively. Prior to SBRT,10 patients (67%) had elevated PIVKA-II (PIVKA+) and 10 (67%) had elevated AFP (AFP+); 7 patients (47%) were PIVKA+ and AFP+ (PIVKA+/AFP+). Elevated pre-SBRT PIVKA-II was present in all patients with MVI and correlated with larger mean tumor size (5.82±0.79 vs 2.20±0.33). Post-SBRT biomarker data was available in 5 patients: 3 PIVKA+/AFP+, 1 PIVKA+/AFP-, and 1 PIVKA-/AFP+. The median decrease in PIVKA-II and AFP post-SBRT was 42.8 ng/ml and 11.5 ng/ml, respectively. At 3 months, 3 out of 3 evaluable PIVKA+ patients (1 missing data) had decreased PIVKA-II levels with median decrease of 91% and had concordant imaging with LR-TR non-progressing despite APHE. At 6 months, PIVKA-II levels were decreased in 3 out of 3 evaluable PIVKA+ patients (1 missing data) with a median decrease of 28%, whereas only 2 out of 4 AFP+ patients had decreased AFP. On imaging, all 3 PIVKA+/AFP+ lesions were LR-TR non progressing with corresponding decrease in PIVKA-II (100%), but only 1 had a concordant decrease in AFP (33%).
Conclusion: PIVKA-II correlates with more aggressive HCC features such as larger tumor size and MVI. In addition, PIVKA-II may have clinical utility in assessing the early treatment response post-SBRT, especially with APHE and persistent washout. Further studies are needed to validate the clinical utility of PIVKA-II in HCC treated with SBRT and its complementary role to AFP and magnetic resonance imaging.