Modeling Hepatocellular Carcinoma Cells Dynamics by Serological and Imaging Biomarkers to Explain the Different Responses to Sorafenib and Regorafenib
| Autor: | Veronica Romagnoli, Daniela Cavallone, Patrizia Bleve, Piero Boraschi, A. Salvati, L. Civitano, G. Ricco, Paola Scalise, Coskun Ozer Demirtas, Ferruccio Bonino, Piero Colombatto, Lucio Urbani, Barbara Coco, Filippo Oliveri, Maurizia Rossana Brunetto |
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| Přispěvatelé: | Colombatto, Piero, Demirtas, Coskun Ozer, Ricco, Gabriele, Civitano, Luigi, Boraschi, Piero, Scalise, Paola, Cavallone, Daniela, Oliveri, Filippo, Romagnoli, Veronica, Bleve, Patrizia, Coco, Barbara, Salvati, Antonio, Urbani, Lucio, Bonino, Ferruccio, Brunetto, Maurizia Rossana |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Oncology
Sorafenib Cancer Research medicine.medical_specialty AFP digital imaging HYPOXIA Vitamin k Tumor vasculature Article Serology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine GAMMA-CARBOXY PROTHROMBIN Regorafenib Internal medicine PIVKA-II Medicine HCC TUMOR PROGRESSION RC254-282 business.industry mathematical modeling Neoplasms. Tumors. Oncology. Including cancer and carcinogens hepatocellular carcinoma medicine.disease chemistry kinetics 030220 oncology & carcinogenesis Hepatocellular carcinoma Serological biomarkers Cancer cell SURVIVAL 030211 gastroenterology & hepatology sorafenib regorafenib business medicine.drug |
| Zdroj: | Cancers Cancers, Vol 13, Iss 2064, p 2064 (2021) Volume 13 Issue 9 |
| Popis: | Simple Summary Systemic therapy in advanced hepatocellular-carcinomas (HCC) has limited benefits, but some patients show partial responses (PR) and a few even a complete response (CR). Understanding the biological mechanisms could help clinicians in decision-making. Aim of this study was to develop a physic-mathematical model to investigate tumor dynamics using alpha-fetoprotein (AFP) and protein induced by vitamin K absence-II (PIVKA-II) measures combined with digital imaging. The model was set-up in three prototype patients with CR/PR to sorafenib and PR to regorafenib, and then applied in seven patients with different types of response. Overall, the rate constant of cancer cells production ranged between 0.250-0.372 C x day(-1). During therapy, neo-angiogenesis reduction was higher in four CR than in four PR or stable disease (SD) and in two non-responders (median: 83.2% vs. 29.4% vs. 2.0%). Tumor vasculature decay appeared accelerated in CR. We conclude that modeling serological and imaging biomarkers could help personalization of systemic therapy. In advanced HCC, tyrosine-kinase inhibitors obtain partial responses (PR) in some patients and complete responses (CR) in a few. Better understanding of the mechanism of response could be achieved by the radiomic approach combining digital imaging and serological biomarkers (alpha-fetoprotein, AFP and protein induced by vitamin K absence-II, PIVKA-II) kinetics. A physic-mathematical model was developed to investigate cancer cells and vasculature dynamics in three prototype patients receiving sorafenib and/or regorafenib and applied in seven others for validation. Overall four patients showed CR, two PR, two stable-disease (SD) and two progressive-disease (PD). The rate constant of cancer cells production was higher in PD than in PR-SD and CR (median: 0.398 vs. 0.325 vs. 0.316 C x day(-1)). Therapy induced reduction of neo-angiogenesis was greater in CR than in PR-SD and PD (median: 83.2% vs. 29.4% and 2.0%), as the reduction of cell-proliferation (55.2% vs. 7.6% and 0.7%). An additional dose-dependent acceleration of tumor vasculature decay was also observed in CR. AFP and cancer cells followed the same kinetics, whereas PIVKA-II time/dose dependent fluctuations were influenced also by tissue ischemia. In conclusion, pending confirmation in a larger HCC cohort, modeling serological and imaging biomarkers could be a new tool for systemic therapy personalization. |
| Databáze: | OpenAIRE |
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