Treatment variables related to liver toxicity in patients with hepatocellular carcinoma, Child-Pugh class A and B enrolled in a phase 1-2 trial of stereotactic body radiation therapy. Practical radiation oncology Lasley, F. D., Mannina, E. M., Johnson, C. S., Perkins, S. M., Althouse, S., Maluccio, M., Kwo, P., Cárdenes, H. 2015; 5 (5): e443-9


An analysis was performed on patients enrolled in a phase 1-2 trial using stereotactic body radiation therapy for hepatocellular carcinoma evaluating variables influencing liver toxicity.Thirty-eight Child-Pugh class A (CPC-A) (39 lesions) and 21 CPC-B patients (26 lesions) were followed for =6 months. Six months local control using modified Response Evaluation Criteria in Solid Tumors criteria, progression-free survival, overall survival, and grade III/IV treatment-related toxicity at 3 months were analyzed.Median follow-up was 33.3 months (2.8-61.1 months) for CPC-A and 46.3 months (3.7-70.4 months) for CPC-B patients. Local control at 6 months was 92% for CPC-A and 93% for CPC-B. Kaplan-Meier estimated 2- and 3-year local control was 91% for CPC-A and 82% for CPC-B (P = .61). Median overall survival was 44.8 months and 17.0 months for CPC-A and CPC-B. Kaplan-Meier estimated 2- and 3-year overall survival was 72% and 61% for CPC-A and 33% and 26% for CPC-B (P = .03). Four (11%) CPC-A patients and 8 CPC-B patients (38%) experienced grade III/IV liver toxicity. Overall, CPC-A patients with =grade III liver toxicity had 4.59 (95% confidence interval, 1.19-17.66) times greater risk of death than those without toxicity (P = .0268). No such correlation was seen for CPC-B patients; however, 3 of these CPC-B patients underwent orthotopic liver transplant. CPC-B patients experiencing grade III/IV liver toxicity had significantly higher mean liver dose, higher dose to one-third normal liver, and larger volumes of liver receiving doses <2.5 to 15 Gy in 2.5-Gy increments. For CPC-A patients, there was no critical liver dose or volume constraint correlated with toxicity.In our experience, liver stereotactic body radiation therapy is a safe therapy for patients with hepatocellular carcinoma in the context of liver cirrhosis; however, for CPC-B patients, careful attention should be paid to low-dose volumes that could potentially result in increased liver toxicity.

View details for DOI 10.1016/j.prro.2015.02.007

View details for PubMedID 25899219