A precision image-guided murine model of stereotactic ablative radiotherapy for hepatocellular carcinoma.

Abstract

Liver tumours, both primary and metastatic, are diseases of unmet clinical need. Hepatocellular carcinoma (HCC) the most common primary liver tumour, like many other cancers, may be treated by stereotactic ablative radiotherapy (SABR), reducing off-target effects of radiation on local anatomical structures. However, integrating all the necessary components for stereotactic irradiation of hepatocellular carcinoma in murine models has not yet been reported. Here we provide the development and detailed characterisation of a murine SABR model combining both MRI and CT image-guided delineation of the tumour, together with CT-guided liver tumour radiotherapy. The model enables accurate delivery of clinically relevant doses of radiotherapy with good tolerability and on-target tumour responses in models with otherwise universally progressive disease. The development of this preclinical modelling platform paves the way for its integration into multimodal therapeutic and mechanistic testing in preclinical murine models of both metastatic and primary liver tumours, including hepatocellular carcinoma.