Gallbladder Toxicity and High Dose Ablative-Intent Radiation for Liver Tumors: Should We Constrain the Dose?

Publication date: Available online 9 February 2017
Source:Practical Radiation Oncology
Author(s): Shyam K. Tanguturi, Andrzej Niemierko, Jennifer Y. Wo, Khanhnhat N. Nguyen, Hugh Prichard, Andrew X. Zhu, John A. Wolfgang, Theodore S. Hong
Purpose/Objectives(s)Little is known about the risk of gallbladder toxicity from hypofractionated (HFXRT) and stereotactic body radiotherapy (SBRT). We report on gallbladder toxicity and attribution to treatment in a prospective series of patients with primary and metastatic liver tumors receiving ablative-intent HFXRT and SBRT with protons.Methods and MaterialsWe evaluated 93 patients with intact gallbladders enrolled in either of two trials investigating proton HFXRT and SBRT for primary and metastatic liver tumors from 2009–2014. Patients received 45–67.5 GyE in 15 fractions for primary liver tumors (n=45) and 30–50 GyE in 5 fractions for metastatic tumors (n=48). No gallbladder dose constraints were used at treatment, and gallbladder volumes and dose-volume histograms were created retrospectively. Attributable toxicity was defined as cholecystitis or perforation without pre-existing gallbladder disease. Baseline factors were evaluated using Fisher's exact test and the nonparametric K-sample test.ResultsAt baseline, 25 patients had pre-existing cholelithiasis and 15 underwent biliary stenting before or after RT. Median follow-up after treatment was 11.8months (range: 0.1–59.2months). Despite maximum gallbladder doses >70 GyE in 41%, >80 GyE in 31% and >90GyE in 13% (EQD2, α/β=3), there were no attributable cases of gallbladder toxicity. Two patients developed grade 3 and 4 cholecystitis 16 and 2months after treatment, and both had a strong history of pre-existing cholelithiasis and biliary stenting. These patients received relatively low gallbladder doses with mean doses of 0.02 GyE and 5.1 GyE (EQD2, α/β=3), well below the 17.1 GyE mean for the remaining cohort (range: 0–81.1 GyE, EQD2).ConclusionsWe identified no relationship between gallbladder dose and toxicity and did not reach the maximum tolerated gallbladder dose in this cohort treated with high-dose radiation. We recommend not constraining dose to the gross tumor volume to protect the gallbladder during ablative HFXRT and SBRT.



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