Tolerance of Liver as a Predictor of Hepatic Dysfunction in 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 with high doses may render cirrhotic liver more susceptible to RT-induced liver injury than normal liver parenchyma. We investigated and analyzed the hepatic dysfunction associated with the dose distribution by MRI using the hepatocyte-targeted Gd-EOB-DTPAwhich has a similar feature to ICG (indocyanine green) for the liver function test. Materials/Methods: A total of 64 liver cancer patients were treated by SBRT. Of these patients, 54 were hepatocellular carcinoma (HCC) in liver cirrhosis, and 10 were metastatic cancer in normal liver. The median PTV volumes were 33.0cm3 (8.7-232.9) with HCC and 64.4cm3 (8.5-204.5) with liver metastases. The median prescribed dose delivered to the PTV was 44.0Gy (40.0-55.5) for HCC and 55.5Gy (48.0-65.0) for liver metastases, with median fraction size of 5.0Gy (4.0-15.0) and 5.5Gy (4.025.0), respectively. 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 which was injected twenty minutes before the image acquisition. All MRI data sets were merged with 3D-dosimetry data by using in-house DICOM-RT image fusion software which also 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 2Gy for intercomparing over a wide variety of dose distribution around the border. Results: The registration error was 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 BED2 provoking hepatic dysfunction was a median of 92Gy (70-179) in normal liver. However, in cirrhotic liver, it was significantly decreased to a median of 56Gy (30-228) which shows that the hypersensitivity to radiation lowered the threshold dose for hepatic dysfunction. Conclusions: The fundamental premise for liver SBRT is to preserve adequate liver function, therefore, pretreatment validation of the future liver remnant volume is critical. In this study, tolerance of liver was evaluated as a predictor of hepatic dysfunction in SBRT. The critical dose provoking hepatic dysfunction was estimated to be 56Gy (BED2) in cirrhotic liver which was about half of the dose with normal liver. Author Disclosure: R. Oh: None. H. Shiomi: None. Y. Imai: None. D. Tatsumi: None. N. Masai: None. T. Inoue: None.