SELECTIVE INTERNAL RADIATION-THERAPY FOR NONRESECTABLE HEPATOCELLULAR-CARCINOMA WITH INTRAARTERIAL INFUSION OF (90)YTTRIUM MICROSPHERES

Purpose: To evaluate the efficacy of intraarterial (90)yttrium (Y-90) microspheres in nonresectable hepatocellular carcinoma (HCC). Methods and Materials: Patients with nonresectable HCC, but without extrahepat ic disease, who also had lung shunting <15% and tumor-to-normal ratio greater than or equal to 2, as determined by simulation using (99m)tec hnetium macroaggregated albumin, were entered into the study. The radi ation dose delivered to the lungs, tumor, and normal liver ,vas estima ted by a partition model. Y-90 microspheres were infused into the hepa tic artery at the time of hepatic angiography or through an implanted arterial portacatheter under fluoroscopy. Repeated treatments were giv en for residual or recurrent tumor. Response to treatment was monitore d by serum alpha-fetoprotein or ferritin revels, together with serial computed tomography. Results: Seventy-one patients, including 20 patie nts with postoperative recurrence, were initially treated with an acti vity of 0.8 to 5.0 Giga-Becquerel (GBq) (21.6-135.1 mCi) (median 3.0 G Bq or 81.1 mCi) of Y-90 microspheres. There was a 50% reduction in tum or volume in 19 (26.7%) patients after the first treatment. However, t he overall objective response in terms of changes in alpha-fetoprotein levels was 89% [partial response (PR) 67%, complete response (CR) 22% ] among the 46 patients with raised pretreatment levels. The serum fer ritin level in the other 25 patients dropped by 34 to 99% after treatm ent, Treatment was repeated in 15 patients. The maximum number of trea tments was 5 and the maximum total activity was 13.0 GBq (351.4 mCi), given in 3 treatments. The estimated radiation doses to the nontumorou s liver ranged from 25 to 136 Gy (median 52 Gy) in the first treatment and the highest total radiation dose was estimated to be 324 Gy. For the tumors, the estimated radiation doses ranged from 83 to 748 Gy (me dian 225 Gy) in the initial treatment and the highest cumulative dose reached was 1580 Gy. The residual tumors were resected in 4 patients. Two of these had complete histological remission, but only occasional viable tumor cells were found in the necrotic centers of the tumors re sected from the other 2 patients. The median survival of the 71 patien ts was 9.4 months (range 1.8 to 46.4 months). Treatment was well toler ated and there was no bone-marrow toxicity, or clinical evidence of ra diation hepatitis or pneumonitis. Conclusions: Selective internal radi ation therapy using Y-90 microspheres is effective for selected cases of nonresectable HCC and is web tolerated. The objective response rate in terms of drop in tumor marker levels is higher than that based on reduction in tumor volume shown by computed tomography. The nontumorou s liver appears more tolerant to internal radiation than external beam radiation. Selective internal radiation treatment may convert nonrese ctable tumors to resectable ones. (C) 1998 Elsevier Science Inc.