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The treatment of hepatic tumors remains unsatisfactory. These lesions receive most of their blood supply from the hepatic artery, therefore the hepatic artery administration of beta-emitting particulate radiopharmaceuticals is an attractive approach to deliver therapeutic irradiation to the liver and differentially to tumors within the liver.A Phase I dose escalation study of the hepatic tolerance to radiation delivered by 90Y containing glass microspheres was carried out in 24 patients with hepatic malignancy. Doses of 90Y microspheres to achieve an estimated whole-liver nominal absorbed radiation dose of 5000 cGy (two patients), 7500 cGy (six patients), 10,000 cGy (seven patients), 12,500 cGy (six patients), and 15,000 cGy (three patients) were administered via the hepatic artery. The administered nominal absorbed radiation dose (NARD) was estimated based on liver volume determined from CT scans and the assumption of uniform distribution of microspheres throughout the liver.No hematologic, hepatic or pulmonary toxicity was encountered in the dose range examined during a mean follow-up period of up to 53 mo. Reversible gastritis or duodenitis was encountered in four patients without imaging or biopsy evidence for extrahepatic deposition of microspheres. Response data, based on CT scans obtained 16 wk after treatment, showed progressive disease in eight patients, stable disease in seven patients, minimal response in four patients and partial response in five patients. Subsequent follow-up revealed three long-term survivors at 204, 216 and 228 wk.These preliminary data demonstrate that in the examined dose range, radiation may be safely delivered to liver tumors by means of 90Y glass microspheres with encouraging response data.

The nonuniformity of dose deposition for hepatic 90Y-microsphere therapy is believed to play an important role in the relative sparing of normal liver tissues. To help study this issue, three-dimensional dose calculations have been performed for the VX2 tumor model in the rabbit treated with hepatic arterial administration of 90Y-glass microspheres (90Y-MS). Colored, nonactivated spheres of similar size to 90Y-MS were injected into the hepatic artery to mimic the treatment deposition of 90Y-MS. Sample blocks of treated liver were serially sectioned (200 microns thickness), fixed and photographed showing the position of the colored microspheres. The microsphere positions were digitized into a three-dimensional treatment planning system, and three-dimensional dose calculations were performed. A 2-mm diameter liver tumor nodule receiving 15 times more microspheres than nearby normal liver resulted in tumor-to-normal-tissue (TNT) calculated dose ratios of 2.6 (average dose) and 1.9 (minimum dose). The nonuniform microsphere distribution resulted in a dose gradient over the nodule with a minimum value which was less than one half the average dose. The relative dose deposition in the vicinity of the tumor nodule does not fully reconcile the known liver tolerance dose derived from uniform irradiation with the large calculated average doses tolerated with this type of therapy.

Hepatic arterial infusion chemotherapy results in a higher concentration of drug delivered to the tumor with less systemic exposure than is possible with intravenous therapy. However, extrahepatic blood flow and/or shunting to the lung can impose a limitation. This study describes a quantitative method for calculating the extrahepatic component and monitoring its changes due to a new adjunctive therapy, degradable starch microspheres (DSM). DSM temporarily occlude the hepatic arterial circulation, thereby increasing the uptake of therapeutic drugs. Twenty patients with metastatic liver cancer underwent hepatic arterial perfusion scintigraphy (HAPS) using Tc-99m MAA to determine blood-flow distribution and to quantitate extrahepatic uptake. The percent shunt index (PSI) was determined at baseline and after each incremental dose of DSM. The baseline PSI ranged from 6-26% (mean 12.3 +/- 5.8 s.d.) and changed progressively after each injection of DSM/Tc-MAA suspension. The patterns of change in shunting are described. Quantitative HAPS provides a means of measuring the extrahepatic component, warns of potential side effects, and helps guide chemotherapeutic decisions.

In 17 patients receiving regional hepatic chemotherapy, Tc-99m macroaggregated albumin imaging was used to aid arterial catheter placement and to assess perfusion patterns. Intraoperative imaging with a portable gamma camera allowed immediate monitoring of hepatic and extrahepatic perfusion patterns and assisted catheter manipulation when necessary to achieve optimal flow distribution. In all 12 patients with standard hepatic arterial anatomy, complete perfusion of both lobes of the liver was achieved, although three of them required intraoperative catheter manipulation and repeat imaging after initial placement. The remaining five patients had aberrant hepatic arterial anatomy, and complete perfusion was more difficult to achieve; they exemplified the need for dual catheters, ligation of accessory hepatic branches, and repeated imaging.