Precision Oncology With Radiogenomics: Non-invasive Interrogation of Liver Cancer Genomics to Select Drug Therapy and Monitor Patient Response

Background: Significant intratumoral heterogeneity is present in hepatocellular carcinoma (HCC) and single biopsy samples severely underread the genomic profile of the tumor. This confounds drug development in HCC and makes it extremely challenging to stratify and prognosticate patients to select therapy on the basis of genomic biomarkers. Multiregion sampling of surgically resected HCC allows for these intratumoral heterogeneity to be unraveled and this is currently carried out in our prospective PLANET (Precision Medicine in Liver Cancer across an Asia-Pacific Network) program. However, multiregion sampling is not practical in unresectable HCC cases, which comprise 80% of the disease burden. Radiogenomics studies on liver, lung and head-and-neck cancers have established the capability of radiomics analysis in capturing intratumor heterogeneity with the identification of radiomics signatures that are representative of underlying gene expression patterns. Aim: On this basis, our PLANET program has adopted a radiogenomics approach to characterize the intratumoral heterogeneity in HCC. Methods: This approach will leverage on the correlation of distinctive imaging traits in CT scans against the gene expression profiles of surgically resected HCC patients. Our PLANET program and the data-science enterprise Holmusk have embarked on close collaborative efforts to develop an algorithm that characterizes intratumoral heterogeneity based on distinctive traits in the CT scans. Results and conclusion: The development of such an algorithm is potentially ground-breaking as it allows for the noninvasive interrogation of liver cancer genomics and prognostication of HCC patients. This allows the easy screening of patients for therapeutic targets in vivo and will significantly improve the selection of drug therapy and monitoring of therapeutic response in HCC.