Radiation Dose Limits and Liver Toxicities Resulting from Multiple Yttrium-90 Radioembolization Treatments for Hepatocellular Carcinoma

Purpose: To assess the relationship between cumulative hepatic lobar radiation dose and liver toxicities in patients with hepatocellular carcinoma (HCC) treated with multiple sessions of yttrium-90 radioembolization. Materials and Methods: Forty-one patients with HCC (age range, 46-82 years) underwent radioembolization with ⁹⁰Y. Patients were classified according to the Okuda scoring system. All patients received single liver lobar treatments on two or more occasions according to standard clinical ⁹⁰Y embolization protocol. Cumulative radiation dose to each liver lobe was measured and patients were followed to assess liver toxicities. Statistical analysis was performed with the Student t test and Kaplan-Meier analysis. Results: Patients with Okuda stage I disease received more treatments than those with Okuda stage II disease (mean, 2.65 vs 2.24; P < .05). For average cumulative radiation dose, patients with Okuda stage I disease received 247 Gy (range, 88-482 Gy) and those with Okuda stage II disease received 198 Gy (range, 51-361 Gy; P < .05). A total of 13 toxicities occurred in seven patients (16%). Patients with Okuda stage I disease were given a greater cumulative dose than patients with Okuda stage II disease before worsening of liver function: 390 Gy versus 196 Gy (P < .005). For patients with Okuda stage I disease, a higher cumulative radiation dose was associated with occurrence of one or more toxicities: 222 Gy (no toxicities) versus 390 Gy (≥1 toxicity; P < .005). No correlation between cumulative radiation dose and liver toxicities existed in patients with Okuda stage II disease. The maximum tolerated dose was between 222 and 390 Gy. Median survival times were 660 and 431 days for patients with Okuda stage I and stage II disease, respectively. Conclusions: Patients with HCC can tolerate high cumulative radiation doses with ⁹⁰Y therapy. Compared with patients with Okuda stage II disease, patients with Okuda stage I disease tolerate a higher cumulative radiation dose without liver toxicity, but liver toxicities increase with increasing cumulative radiation doses.