Abstract
Simple SummaryRadioembolization of hepatic tumors is performed by injecting 90Y or 166Ho loaded spheres into the hepatic artery. A twofold tumor to normal liver absorbed dose ratio is commonly obtained. In order to improve tumoral cell killing while preserving lobule function, co-injection of arterial vasoconstrictor has been proposed, but without success: the hepatic arterial buffer response quickly inhibits the arterioles vasoconstriction. The aim of the study is to investigate whether it is possible to take benefit from this buffer response, by co-infusing a mesenteric arterial vasodilator in order to dump the hepatic lobules arterial flow. Animal studies evidencing such mechanism are reviewed. Some potential mesenteric vasodilators are identified and their safety profile discussed. A four to sixfold improvement of the tumoral to normal tissue dose ratio is expected, pushing the therapy towards a real curative intention, especially in hepatocellular carcinoma (HCC), more frequent in obese subjects, and where ultra-selective spheres delivery is often not possible.Liver radioembolization is a treatment option for unresectable liver cancers, performed by infusion of 90Y or 166Ho loaded spheres in the hepatic artery. As tumoral cells are mainly perfused via the liver artery unlike hepatic lobules, a twofold tumor to normal liver dose ratio is commonly obtained. To improve tumoral cell killing while preserving lobules, co-infusion of arterial vasoconstrictor has been proposed but with limited success: the hepatic arterial buffer response (HABR) and hepatic vascular escape mechanism hamper the arterioles vasoconstriction. The proposed project aims to take benefit from the HABR by co-infusing a mesenteric arterial vasodilator: the portal flow enhancement inducing the vasoconstriction of the intra sinusoids arterioles barely impacts liver tumors that are mainly fed by novel and anarchic external arterioles. Animal studies were reviewed and dopexamine was identified as a promising safe candidate, reducing by four the hepatic lobules arterial flow. A clinical trial design is proposed. A four to sixfold improvement of the tumoral to normal tissue dose ratio is expected, pushing the therapy towards a real curative intention, especially in HCC where ultra-selective spheres delivery is often not possible.
Highlights
Liver radioembolization using 90 Y or 166 Ho loaded spheres injected via the hepatic artery is an evolving technique for primary and secondary liver tumors treatment [1].Normal liver tissue is mainly fed by the portal vein
2.1 ± 1.3 and 1.8 ± 0.9 are commonly reached in hepatocellular carcinoma (HCC) and in secondary colorectal cancer (CRC) tumors [2], respectively
The goal of the present study is to investigate how benefit could be taken from the hepatic arterial buffer response (HABR) by co-infusing a mesenteric arterial vasodilator
Summary
Liver radioembolization using 90 Y or 166 Ho loaded spheres injected via the hepatic artery is an evolving technique for primary and secondary liver tumors treatment [1].Normal liver tissue is mainly fed by the portal vein. Liver radioembolization using 90 Y or 166 Ho loaded spheres injected via the hepatic artery is an evolving technique for primary and secondary liver tumors treatment [1]. Tumors, in order to sustain their high metabolism, trigger arterial angiogenesis by releasing vascular endothelial growth factor (VEGF). A tumor to normal tissue dose ratio (T/N) of about. The maximal tumor dose reachable is limited by the need to preserve the remaining functional liver tissue. Contrary to external beam radiotherapy (EBRT), where uniform dose deposition is feasible, the tumor-absorbed doses in radioembolization are very heterogeneous due to the random nature of sphere dynamic transport in the arterial tree [3]. Tumor-absorbed doses above 200 Gy are required in order to get significant patient outcome improvement [4]
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