Previous external beam radiation therapy (EBRT) is theoretically contraindicated for yttrium-90 ((90)Y) radioembolization (RE) because the liver has a lifetime tolerance to radiation before becoming vulnerable to radiation-induced liver disease. We analyzed the safety of RE as salvage treatment in patients who had previously undergone EBRT.

Between June 2004 and December 2010, a total of 31 patients who had previously undergone EBRT were treated with RE. Three-dimensional treatment planning with dose-volume histogram (DVH) analysis of the liver was used to calculate the EBRT liver dose. Liver-related toxicities including RE-induced liver disease (REILD) were reviewed and classified according to Common Terminology Criteria for Adverse Events version 4.02.

The mean EBRT and RE liver doses were 4.40 Gy (range, 0-23.13 Gy) and 57.9 Gy (range, 27.0-125.9 Gy), respectively. Patients who experienced hepatotoxicity (≥grade2; n=12) had higher EBRT mean liver doses (7.96 ± 8.55 Gy vs 1.62 ± 3.39 Gy; P=.037), the only independent predictor in multivariate analysis. DVH analysis showed that the fraction of liver exposed to ≥30 Gy (V30) was the strongest predictor of hepatotoxicity (10.14% ± 12.75% vs 0.84% ± 3.24%; P=.006). All patients with V30 >13% experienced hepatotoxicity. Fatal REILD (n=2) occurred at the 2 highest EBRT mean liver doses (20.9 Gy and 23.1 Gy) but also at the highest cumulative liver doses (91.8 Gy and 149 Gy).

Prior exposure of the liver to EBRT may lead to increased liver toxicity after RE treatment, depending on fractional liver exposure and dose level. The V30 was the strongest predictor of toxicity. RE appears to be safe for the treatment of hepatic malignancies only in patients who have had limited hepatic exposure to prior EBRT.