Impact of Radiotherapy on ctDNA in Patients With Hepatocellular Carcinoma

Radiotherapy is increasingly being used in the management of hepatocellular carcinoma (HCC) as a standalone treatment, or in combination with systemic therapy. Stereotactic Body Radiation Therapy (SBRT) causes cell death directly (via double-stranded breaks) and indirectly (via vascular bed damage or promotion of antitumour immunity). Unfortunately, the effect of cell death is not immediate and takes time. As a result, the typical arterial phase hyperenhancement on imaging may persist up to 12 months after radiotherapy, and it is not necessarily suggestive of presence of viable tumours. Therefore, there is no consensus on ideal timing of response assessment following radiotherapy to HCC. Therefore, a blood-based biomarker which can be done frequently and monitored dynamically, could be preferred for response assessment after radiotherapy. Circulating tumour DNA (ctDNA) is an emerging and promising biomarker in cancer management, which has been shown useful in cancer screening, guiding treatment, and informing prognosis. Currently, most of the clinical applications of ctDNA revolve around either the presence of ctDNA, or the genomic changes associated with these molecules. Biological properties of ctDNA such as fragment length, jaggedness of fragments, or epigenetic changes may provide additional information related to the tumour characteristics and its sensitivity to anti-cancer treatments. These biological properties of ctDNA are relatively unexplored in the context of radiotherapy. It is unknown whether these properties can be utilized for monitoring treatment response. We therefore propose to study the biological properties of ctDNA in relation to HCC patients undergoing radiotherapy.