A multicenter study was sponsored by the International Atomic Energy Agency (IAEA) to assess the safety and efficacy of transarterial rhenium-188 (188Re) HDD lipiodol (radioconjugate to lipiodol using an HDD kit) in the treatment of unresectable hepatocellular carcinoma. During 5 years, 185 patients received at least 1 treatment of radioconjugate, and 51 were retreated. The level of radioconjugate administered was based on radiation-absorbed dose to critical normal organs, calculated after a "scout" dose of radioconjugate. The total injected activity, including the scout dose during the first treatment, ranged from 21 to 364 mCi (mean, 108 mCi/4 GBq). Immediate and late side-effects were minimal. Tumor size could be evaluated in 88 patients. Among these patients, the objective response rate was 25%; stable disease was observed in 53% and tumor progression in 22%. With a median follow-up of 455 days, the estimated 12- and 24-month overall survival was 46% and 23%. This multicenter study shows that 188Re lipiodol is a safe and cost-effective method to treat primary hepatocellular carcinoma via the transarterial route and requires further evaluation by treatment of greater numbers of patients.

PURPOSE:Intra-arterial injections (IAI) of 131I-lipiodol is effective in treating hepatocellular carcinoma patients, but is expensive and requires a 7-day hospitalization in a radioprotection room. 188Re is inexpensive, requires no patient isolation, and can be used with lipiodol. METHODS AND MATERIALS:This International Atomic Energy Agency-sponsored phase II trial aimed to assess the safety and the efficacy of a radioconjugate 188Re + lipiodol (188Re-Lip) in a large cohort of hepatocellular carcinoma patients from developing countries. A scout dose is used to determine the maximal tolerated dose (lungs <12 Gy, normal liver <30 Gy, bone marrow <1.5 Gy) and then the delivery of the calculated activity. Efficacy was assessed using response evaluation criteria in solid tumor (RECIST) and alpha-feto-protein (alpha FP) levels and severe adverse events were graded using the Common Toxicity Criteria of the National Cancer Institute scale v2.0. RESULTS:The trial included 185 patients from eight countries. The procedure was feasible in all participating centers. One treatment was given to 134 patients; 42, 8, and 1 received two, three, and four injections, respectively. The injected activity during the first treatment was 100 mCi. Tolerance was excellent. We observed three complete responses and 19 partial responses (22% of evaluable patients, 95% confidence interval 16-35%); 1- and 2-year survivals were 46% and 23%. Some factors affected survival: country of origin, existence of a cirrhosis, Cancer of the Liver Italian Program score, tumor dose, absence of progression, and posttreatment decrease in alpha FP level. CONCLUSIONS:IAI of 188Re-Lip in developing countries is feasible, safe, cost-effective, and deserves a phase III trial.

PURPOSE To prospectively evaluate, in a multicenter clinical trial, dosimetry-guided transarterial radionuclide therapy (TART) with rhenium 188 ((188)Re) 4-hexadecyl 1,2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol (HDD)-labeled iodized oil in inoperable hepatocellular carcinoma (HCC). MATERIALS AND METHODS Ninety-three patients were recruited from 2000 to 2005 for this ethics committee-approved study. Informed written consent was obtained. After complete clinical evaluation (including assessment of liver status, serum alpha-fetoprotein [AFP] level, tumor size, portal vein status, Child-Pugh classification, Okuda staging), radiation absorbed dose (RAD) to various organs, including tumor, was calculated after injecting 185 MBq of (188)Re HDD iodized oil via the hepatic artery. From this value, the maximum tolerable activity of (188)Re, defined as the amount of radioactivity delivering no more than 12 Gy of RAD to lungs, 30 Gy to normal liver, or 1.5 Gy to bone marrow, was calculated and injected. RESULTS Mean patient age was 53 years (80 men and 13 women). Sixty-eight percent of patients had serologic evidence of hepatitis B and/or C; 40% had clinicoradiologic evidence of cirrhosis. Mean tumor diameter was 10.3 cm +/- 4.4, with 40% of patients having more than three lesions; in 50% of patients, tumor was either unilateral, occupying 50% or more of the liver, or bilateral. AFP was elevated in 68% of patients and was elevated to more than 300 ng/mL in 44% of patients. There was portal vein thrombosis in 38% of patients, Child-Pugh status B disease in 37% of patients, and Okuda stage II or III disease in 50% of patients. Mean first administered activity was 5.3 GBq +/- 1.6, which delivered 88 Gy of RAD to the tumor. Treatment was tolerated well. Of 66 patients in whom complete tumor response occurred, five (8%) had complete tumor mass ablation, 17 (26%) had a partial response (>50% tumor reduction), and 23 (35%) had stable disease. Only RAD to the tumors was found to be significantly (P = .001) associated with tumor and/or AFP response. Survival rates at 6, 9, 12, 24, and 36 months among patients with objective tumor response were 100%, 95%, 90%, 58%, and 30%, respectively, with a median survival of 980 days. CONCLUSION TART appears to be a safe, effective, and promising therapeutic option in patients with inoperable HCC.

We tried to evaluate the role of dosimetry-guided transarterial radionuclide therapy (TART) with rhenium-188 (Re-188)-4-hexadecyl 1-2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol (HDD)-lipiodol in a patient with multiple intrahepatic recurrences after radiofrequency ablation of hepatocellular carcinoma (HCC). The dosimetry helped in delivering the maximum possible activity of Re-188, thus the radiation-absorbed dose, safely to the tumour without jeopardizing other organs. There was no procedure-related complication and the patient tolerated therapy well with no adverse effects. The lesions were completely ablated with a single dose of Re-188 and the patient has been disease free for the past 18 months. TART with Re-188-HDD-lipiodol appears to be a promising therapeutic option in patients with HCC who experience recurrence after percutaneous ablative therapy.

Surgical resection with partial hepatectomy is the treatment of choice in patients with hepatocellular carcinoma (HCC). However, after recurrence, which is common, such patients have limited therapeutic options. In the present report, transarterial radionuclide therapy (TART) with rhenium 188 HDD-labeled Lipiodol was used to treat a patient with postsurgical recurrence of HCC. The patient tolerated therapy well and the lesions were completely ablated with a single dose of 188Re; the patient is free of disease for 14 months. TART with 188Re-HDD Lipiodol appears to be a promising new therapy in case of HCC recurrence after partial hepatectomy and requires further investigation.

We tried to evaluate the role of dosimetry-guided transarterial radionuclide therapy with rhenium (Re)-188 labeled lipiodol in a patient with unresectable hepatocellular carcinoma and extensive portal vein thrombosis. Dosimetry revealed that the normal liver parenchyma, lungs, bone marrow and the tumor would have received 0.276, 0.141, 0.0006 and 2.95 cGy of radiation absorbed dose per MBq of injected activity. “Maximum tolerated activity” of Re-188, which could have been safely injected to this patient, was calculated to be 8511 MBq with lungs being the dose limiting organ. The dosimetry helped to deliver the maximum possible activity of Re-188, thus radiation absorbed dose into the tumor without jeopardizing healthy liver tissue or other organs. There was no procedure related complication and the patient tolerated therapy well with no adverse effects. His 6.8 cm × 5.7 cm × 5.3 cm tumor, involving segment V–VIII with tumor thrombus in right branch and main portal vein, disappeared completely after two doses (4293 and 4170 MBq, respectively). The treatment appears to be safe, effective and promising as demonstrated by the complete disappearance of tumor along with portal vein thrombus.

Patients with differentiated thyroid cancer may have asymptomatic involvement of renal and/or adrenal gland, particularly if they are elderly and have associated metastases to other organs, which may remain undetected if these patients are not subjected to radioiodine treatment. Our experience also emphasises the role of routine post-radioiodine therapy whole body scan with high degree of clinical suspicion, which may reveal lesions otherwise not discernable in low dose whole body scan. All suspicious lesions should be subjected to structural imaging like ultrasound, CT or MRI for confirmation. In this setting, the role of radioiodine therapy is primarily aimed at palliation that might prolong their survival, probably reduce further spread and thus overall improve the quality of life.