Tolerance of Cirrhotic Liver Comparing With Normal Liver to Stereotactic Body Radiation Therapy

Abstract

Purpose/Objective(s): In recent years stereotactic body radiation therapy (SBRT) has been used to treat liver cancer and has resulted in good outcomes. However, the hepatic tolerance to small volume with hypofractionated high dose irradiation is unclear. Especially partial liver irradiation to high doses may render cirrhotic liver more susceptible to RT-induced liver injury than normal liver. We investigated and analyzed the hepatic radiation injury associated with the dose distribution by using MRI with hepatocyte-targeted Gd-EOB-DTPA. Materials/Methods: A total of 19 liver cancer patients were treated by SBRT. Of these patients, 13 were hepatocellular carcinoma (HCC) in liver cirrhosis, and 6 were metastatic cancer in normal liver. The median prescribed dose delivered to the PTV was 52 Gy (range, 40-56 Gy), with median fraction size of 9 Gy (range, 5-14 Gy) and in a median total irradiation time of 6 days (range, 4-12 days). MRI was performed during 3-6 months after SBRT. MR-sequences were conducted with T1WI with GRE (LAVA; liver acquisition with volume acceleration) enhanced by Gd-EOB-DTPA. All MRI data sets were merged with 3D-dosimetry data by using in-house DICOM-RT image fusion software. The reviewer indicated the border of hypointensity on T1WI (loss of hepatocyte function) and read the isodose line on the border. This boundary doses were corrected to biologically effective dose (BED) using the linear-quadratic (LQ) formulation assuming an a/ b Z 2 Gy for intercomparing over a wide variety of dose distribution around the border. Results: The registration errors were negligible small after image fusion of the planning CT to the follow-up MRI so that the development of hepatocyte dysfunction was definitely validated in correlation to the isodose distribution. The dose per fraction at the border of hepatocyte dysfunction was a median of 4 Gy (range, 2.4-8 Gy). This results indicated that the minimal BED provoking hepatocyte function loss was a median of 105 Gy (range, 70-137 Gy, using LQ formulation, a/b Z 2 Gy) in normal liver. However, in cirrhotic liver, it was significantly decreased to a median of 51 Gy (range, 30-70 Gy, using LQ formulation, a/b Z 2 Gy) so that the toxic effects lowered the threshold dose for hepatic dysfunction in liver cirrhosis. Conclusions: For liver SBRT, the fundamental premise is that to preserve adequate liver function, a minimum volume of normal liver must be spared from receiving a dose that might render it nonfunctional. In this study, the maximum dose allowed to this critical volume was estimated to be 16 Gy in four fractions (BED Z 50 Gy based on LQ conversion, a/b Z 2 Gy) in cirrhotic liver which was half of the BED for normal liver. Author Disclosure: R. Oh: None. H. Shiomi: None. Y. Imai: None. T. Igura: None. Y. Miyata: None. H. Nakamura: None. T. Inoue: None.