Safety of repeated yttrium-90 radioembolization.
OBJECTIVE
Repeated radioembolization (RE) treatments carry theoretically higher risk of radiation-induced hepatic injury because of the liver's cumulative memory of previous exposure. We performed a retrospective safety analysis on patients who underwent repeated RE.


METHODS
From 2004 to 2011, a total of 247 patients were treated by RE. Eight patients (5 men, 3 women, age range 51-71 years) underwent repeated treatment of a targeted territory, all with resin microspheres (SIR-Spheres; Sirtex, Lane Cove, Australia). Adverse events were graded during a standardized follow-up. In addition, the correlation between the occurrence of RE-induced liver disease (REILD) and multiple variables was investigated in univariate and multivariate analyses in all 247 patients who received RE.


RESULTS
Two patients died shortly after the second treatment (at 84 and 107 days) with signs and symptoms of REILD. Both patients underwent whole liver treatment twice (cumulative doses 3.08 and 2.66 GBq). The other 6 patients demonstrated only minor toxicities after receiving cumulative doses ranging from 2.41 to 3.88 GBq. All patients experienced objective tumor responses. In the whole population, multifactorial analysis identified three risk factors associated with REILD: repeated RE (p = 0.036), baseline serum total bilirubin (p = 0.048), and baseline serum aspartate aminotransferase (p = 0.043). Repeated RE proved to be the only independent risk factor for REILD in multivariate analysis (odds ratio 9.6; p = 0.002). Additionally, the administered activity per target volume (in GBq/L) was found to be an independent risk factor for REILD, but only in whole liver treatments (p = 0.033).


CONCLUSIONS
The risk of REILD appears to be elevated for repeated RE. Objective tumor responses were observed, but establishment of safety limits will require improvement in dosimetric measurement and prediction.
Division of Interventional Radiology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305-5642, USA.
Marnix G E H
MG
Lam
John D
JD
Louie
Andrei H
AH
Iagaru
Michael L
ML
Goris
Daniel Y
DY
Sze
D000368:Aged; D001918:Brachytherapy / Q000009:adverse effects* / Q000379:methods; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000532:radiotherapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008099:Liver / Q000528:radiation effects; D008107:Liver Diseases / Q000209:etiology*; D008111:Liver Function Tests / Q000379:methods; D008113:Liver Neoplasms / Q000401:mortality / Q000532:radiotherapy*; D008297:Male; D008863:Microspheres; D008875:Middle Aged; D016017:Odds Ratio; D011832:Radiation Injuries / Q000209:etiology; D019233:Retreatment / Q000009:adverse effects / Q000379:methods; D012189:Retrospective Studies; D012307:Risk Factors; D015021:Yttrium Radioisotopes / Q000009:adverse effects* / Q000627:therapeutic use
D015021:Yttrium Radioisotopes