Treatment of inoperable hepatocellular carcinoma with intrahepatic arterial yttrium-90 microspheres: a phase I and II study

Abstract

SmumuaryEighteen patients with inoperable hepatocellular carcinoma (HCC) were treated with intrahepatic arterial yttrium-90 microspheres. All these patients showed a lung shunting below 15% and a tumour-tonormal ratio higher than 2 as determined by diagnostic technetium-99m macroaggregated albumin (Tc-MAA) gamma scintigraphy. The treatment was given through an arterial port placed during laparotomy. The radiation doses to the liver and tumour were determined intraoperatively with a beta probe and liquid scintillation counting of multiple liver biopsies. The treatment was well tolerated without major complications. In all patients the tumour marker fell to a level which ranged from 41% to 0.2% of the pretreatment level. Tumour regression was found to be dose related. Progressive or static disease occurred in a higher proportion of patients whose tumours received <120 Gy (P = 0.005). Survival was better in those whose tumours received > 120 Gy (median survival = 55.9 weeks) than those whose tumours received lower doses (median survival = 26.2 weeks). This difference is statistically significant with P = 0.005. We conclude that yttrium-90 microsphere therapy is safe and that tumour response is dose related. A tumour dose of > 120 Gy is recommended.Surgery remains the only hope of cure for patients with hepatocellular carcinoma (HCC) (Maclintosh & Minuk, 1992). Unfortunately, most patients have inoperable tumours at the time of presentation, and their prognosis is so dismal that the median survival time is usually less than 2 months (Okuda et al., 1985; Shiu et al., 1990), although longer survivals have been reported in the literature (Yamada et al., 1983;Kajanti et al., 1986;Epstein et al., 1991). Extensive trials with systemic chemotherapy have yielded disappointing results (Friedman. 1983). An increased response rate is reported for hepatic arterial chemotherapy for these tumours, but there is no good evidence that this technique prolongs survival (Malik & Wrigley, 1988).In an attempt to improve on the results of locoregional therapy for inoperable HCC, intrahepatic arterial lipiodol iodine-131 or yttrium-90 microspheres have been used with varying degrees of success (Kobayashi et al., 1986; Park et al., 1987; Bretagne et al., 1988;Houle et al., 1989;Novell et al., 1991). A choice still exists between these two radioisotopes for therapeutic purposes (Park et al., 1987;Novell et al., 1991). Theoretically, yttrium-90 is more suitable for therapy for larger tumours because of its higher energy, thus providing a deeper penetration and a higher tumour dose rate (Park et al., 1987;Lau & Li, 1992). Radiation protection is also easier with a pure beta emitter (Lau & Li, 1992).The safety and efficacy of yttrium-90 microspheres have been attested in clinical studies involving reasonably large numbers of patients with metastatic liver cancer (Blanchard et al., 1989; Gray et al., 1992). The clinical experience in HCC is more limited. A phase I study was conducted on ten patients with HCC to determine the toxicities and tum...

Efficacy and Toxicity Related to Treatment of Hepatocellular Carcinoma with 90Y-SIR Spheres: Radiobiologic Considerations

“…In particular, dose escalation in 10 patients showed that up to 138 Gy to the nontumorous liver by SIR treatment did not cause clinical radiation hepatitis (31). Moreover, 70 Gy by SIR treatment to the nontumorous part of the liver is tolerable in cirrhosis (32). Biopsies in 4 patients receiving up to 75 Gy by SIR treatment showed a minimal histologic effect in the healthy liver (31).…”

GEP-NETS UPDATE: Interventional radiology: role in the treatment of liver metastases from GEP-NETs

“…This results in delivering doses of ionizing radiation above 120 Gy to the tumor compartment without causing intolerable toxicity to the normal liver (60,61). RE demonstrated a close relation between delivered dose and tumor response (62). The dose of the radioactive microspheres is adapted to the lung shunting fraction, if present, and assessed before RE by scintigram obtained after intra-arterial infusion of 99 mTc-macroaggregated albumin (highest tolerable dose of the lung %30 Gy).…”

The effect of intra-arterial angiotensin II on the hepatic tumor to non-tumor blood flow ratio for radioembolization: a systematic review

“…Various studies have found an association between tumor absorbed radiation doses, tumor response and overall survival. [39,40,41,42] It can, therefore, be expected that improved tumor selectivity of radioactive microsphere distribution will positively affect patient outcome after RE.…”