Transarterial radionuclide Re-188-Lipiodol treatment of HCC

Full text: Our study, sponsored by the International Atomic Energy Agency, Vienna aims to assess the safety and efficacy of trans-arterial Re-188 HDD conjugated Lipiodol (radioconjugate) in the treatment of patients with inoperable hepatocellular carcinoma (HCC). A Tungsten (W-188-Re 188) generator was obtained from ORNL (Oak Ridge National Laboratory, Tennessee, USA). The radio-conjugate was prepared by using a HDD (4-hexadecyl 1-2, 9, 9- tetramethyl-4, 7-diaza-1, 10-decanethiol) kit developed in Korea. The level of radio-conjugate administered was based on radiation absorbed dose to critical normal organs, calculated on the basis of a 'scout' dose of radio-conjugate. Specially designed Spreadsheet was used to determine maximum tolerated activity (MTA), defined as the amount of radioactivity calculated to deliver no more than 12 Gray (Gy) to lungs, or 30 Gy to liver, or 1.5 Gy to bone marrow. Possible toxicity from Re-188-HDD-Lipiodol was evaluated by clinical laboratory testing and physical examination, which was performed at 24 hours, one week after therapy and thereafter at every 2-months. In addition, assessment of performance status (Karnovsky), liver function test (Child's classification), serum AFP level test, pulmonary function test and renal function test were performed. Tumor measurements were obtained by CT and US scans every 2-month. Thirty patients with mean age was 58 years (range 46-71) were treated trans-arterially with Re-188-Lipiodol. The treatment activity ranged from 1.7 GBq to 7.4 GBq (46 to 201 mCi) with mean activity of 2.9 GBq (78 mCi). From the spreadsheet, in 18 cases the treatment dose-limiting organ was liver and in 12 cases it was lung. Radiation dose to bone marrow was negligible and was thus not a factor for the MTA calculations. There were no significant side effects but for loss of appetite, right hypochondrial discomfort and low-grade fever, even at high levels of administered radioactivity. In patients with such symptoms simple supportive therapy was given for 1-3 days. Liver function tests and complete blood counts at 24 hrs. and one week showed no significant changes (no bone-marrow suppression). Up to now the follow up after treatment ranges from 3 to 17 months (in 17 cases follow up was 11-17 months and in other cases 3-6 months). Nineteen patients (63%) had stabilization of the disease at three months, while 5 patients (18%) showed partial response, and 6 patients (19%) had disease progression, using CT and US scans measurements. Serum alpha fetoprotein (AFP) levels were elevated in all patients at start of treatment and in 8 of them (40%) the level of AFP decreased two months post-treatment. Survival at 3 months was 100%, and at six months was 77%, while 36% survived for more than 1 year. The results of our study show that Rhenium-188 lipiodol is a safe and cost-effective method to treat primary HCC via the trans-arterial route. However, being a new therapeutic approach, it requires further evaluation in larger numbers of patients. Though the present study is small in its dimension and meta-analysis is not possible, positive results of this clinical trial support the importance of ongoing randomized multi centric clinical trial to investigate further effects of the above-mentioned treatment. (author)