Inoperable hepatocellular carcinoma: transarterial 188Re HDD-labeled iodized oil for treatment--prospective multicenter clinical trial.
OBJECTIVE
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).


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.


CONCLUSIONS
TART appears to be a safe, effective, and promising therapeutic option in patients with inoperable HCC.
Kumar
Ajay
A
Department of Nuclear Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
Srivastava
Deep Narayan
DN
Chau
Trinh Thi Minh
TT
Long
Huynh Duc
HD
Bal
Chandrasekhar
C
Chandra
Prem
P
Chien
Le Truong
le T
Hoa
Nguyen Van
NV
Thulkar
Sanjay
S
Sharma
Sanjay
S
Tam
Le Huu
le H
Xuan
Truong Quang
TQ
Canh
Nguyen Xuan
NX
Pant
Gauri Shankar
GS
Bandopadhyaya
Guru Pad
GP
D006528:Carcinoma, Hepatocellular / Q000532:radiotherapy* / Q000601:surgery; D005260:Female; D006498:Hepatectomy; D006801:Humans; D007269:Injections, Intra-Arterial; D007459:Iodized Oil / Q000008:administration & dosage*; D008113:Liver Neoplasms / Q000532:radiotherapy* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009942:Organometallic Compounds / Q000008:administration & dosage*; D011446:Prospective Studies; D019275:Radiopharmaceuticals / Q000008:administration & dosage; D016896:Treatment Outcome
C498051:188Re-4-hexadecyl-1,2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol lipiodol conjugate; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D007459:Iodized Oil