Predictors of Toxicity Associated With Stereotactic Body Radiation Therapy to the Central Hepatobiliary Tract

Purpose: To identify dosimetric predictors of hepatobiliary ( HB) toxicity associated with stereotactic body radiation therapy ( SBRT) for liver tumors. Methods and Materials: We retrospectively reviewed 96 patients treated with SBRT for primary ( 53%) or metastatic ( 47%) liver tumors between March 2006 and November 2013. The central HB tract ( cHBT) was defined by a 15mm expansion of the portal vein from the splenic confluence to the first bifurcation of left and right portal veins. Patients were censored for toxicity upon local progression or additional liver- directed therapy. HB toxicities were graded according to Common Terminology Criteria for Adverse Events version 4.0. To compare different SBRT fractionations, doses were converted to biologically effective doses ( BED) by using the standard linear quadratic model a/ b Z 10 ( BED10). Results: Median follow- up was 12.7 months after SBRT. Median BED10 was 85.5 Gy ( range: 37.5- 151.2). The median number of fractions was 5 ( range: 1- 5), with 51 patients ( 53.1%) receiving 5 fractions and 29 patients ( 30.2%) receiving 3 fractions. In total, there were 23 ( 24.0%) grade 2_ and 18 ( 18.8%) grade 3_ HB toxicities. Nondosimetric factors predictive of grade 3_ HB toxicity included cholangiocarcinoma ( CCA) histology ( P<. 0001), primary liver tumor ( PZ. 0087), and biliary stent ( P<. 0001). Dosimetric parameters most predictive of grade 3_ HB toxicity were volume receiving above BED10 of 72 Gy ( VBED1072) 21 cm 3 ( relative risk [ RR]: 11.6, P<. 0001), VBED1066 24 cm 3 ( RR: 10.5, P<. 0001), and mean BED10 ( DmeanBED10) cHBT 14 Gy ( RR: 9.2, P<. 0001), with VBED1072 and VBED1066 corresponding to V40 and VBED1072 21 cm 3, VBED1066 24 cm 3, and DmeanBED10 cHBT 14 Gy were consistently predictive of grade 3_ toxicity on multivariate analysis. Conclusions: VBED1072, VBED1066, and DmeanBED10 to cHBT are associated with HB toxicity. We suggest VBED1072 < 21 cm 3 ( 5- fraction: V40 < 21 cm 3; 3- fraction: V33.8 < 21 cm 3), VBED1066 < 24 cm 3 ( 5- fraction: V37.7 < 24 cm 3; 3- fraction: V32 < 24 cm 3) as potential dose constraints for the cHBT when clinically indicated. 2015 Elsevier Inc. All rights reserved.