Dosimetric analysis of liver toxicity after liver metastasis stereotactic body radiation therapy

Purpose The aim of this study is to describe the incidence and type of liver toxicity seen following liver metastases stereotactic body radiation therapy (SBRT) and the corresponding clinical and dosimetric factors associated with toxicity. Methods and materials Between 2002 and 2009, 81 evaluable patients with liver metastases were treated on 2 prospective studies assessing SBRT, with prescription doses based on the effective liver volume irradiated evaluated. Toxicity was defined as grade ≥2 classic or nonclassic radiation induced liver disease (RILD). Specific toxicity endpoints evaluated were worsening transaminases and albumin levels within 3 months of SBRT. Results Seventy percent of patients had colorectal carcinoma, 55% had extrahepatic disease, 1 patient had hepatitis B, and 54% had received prior chemotherapy. Baseline transaminases were elevated at Common Terminology Criteria for Adverse Effects, V4.0, grade 1, 2, and 3 levels in 33 (41%), 2 (2%), and 0 (0%) patients. The mean prescription dose was 43 Gy (27.7-60 Gy) in 6 fractions. The mean liver (minus gross tumor volume) dose (MLD) was 16 Gy (3-25.6 Gy) in 6 fractions. No classic or nonclassical ≥grade 2 RILD was observed. Within 3 months of SBRT, 49 (61%) patients had worsening of grade of transaminase and 23 (28%) patients had a reduction in albumin, all transient (majority grade ≤2 toxicity) without subsequent clinical toxicity. Seventeen patients exceeded Quantitative Analysis of Normal Tissue Effects in the Clinic MLD guidelines (≤20 Gy), 13 (76%) of whom had worsening of transaminase grade. On multivariate analysis, worsening of liver enzymes was more likely in patients with higher doses to the spared 700 mL of liver (P =.026), and reduction of albumin was more likely with higher effective liver volume (odds ratio, 1.53 [range, 1.08-2.16]) P =.016). Conclusions Liver metastases SBRT is safe with a low risk of transient biochemical liver toxicity, more likely in patients with a higher effective liver volume and higher doses to the spared uninvolved liver volume.