Hepatic arterial infusion chemotherapy for unresectable confined liver metastases: prediction of systemic toxicity with the application of a scintigraphic and pharmacokinetic approach

Purpose: The incorrect positioning of the arterial Port-a-Cath or the presence of anatomic or functional hepatic arteriovenous shunting may explain the occurrence of systemic toxicity of hepatic arterial infusion of floxuridine in patients with liver metastases. The aim of our study was to predict the occurrence of systemic toxic effects from this treatment using a scintigraphic and pharmacokinetic approach. Methods: A group of 26 patients were studied. Before treatment, Tc-99m-labelled macroaggregated albumin arterial perfusion scintigraphy was performed to verify the correct positioning of the catheter, to evaluate the percentage of pulmonary uptake of the tracer, reflecting intrahepatic arteriovenous anatomic shunting, and to qualitatively assess the perfusion pattern of the metastases with respect to the normal liver parenchyma (SPECT images). Hepatic arteriovenous functional shunting was assessed through the bioavailability of intraarterially administered D-sorbitol. Treatment was then started and systemic toxic effects were evaluated according to WHO recommendations. Results: No correlation was found between anatomic shunting (≤10% in all patients) and systemic toxicity of treatment. The 9 patients with hypoperfused metastases experienced a significantly lower level of toxic effects (1 low-grade toxicity and 8 no toxicity) than the 17 with hyperperfused metastases (6 high-grade toxicity, 5 low-grade and 6 no toxicity; χ2 = 7.170, P = 0.028). Functional shunting was significantly different in patients with high-grade, low-grade and no toxicity (46.5 ± 19.9%, 15.8 ± 12.7% and 16.5 ± 10.3%, respectively; P<0.001 by analysis of variance). Moreover, functional shunting was significantly greater only in patients with hyperperfused metastases who developed high-grade toxicity. Conclusions: A protocol combining scintigraphic and pharmacokinetic methods is of value in the individual patient in assessing the risk of high-grade systemic toxicity during hepatic arterial infusion of floxuridine. A flow-chart used in our ongoing prospective study for the evaluation of patients undergoing regional chemotherapy for liver metastases is included.