The purpose of this study is to determine if baseline liquid biopsy assays (CTC and cf-DNA) as well as single circulating tumor cell-DNA (sCTC DNA) dynamics in the early post-treatment period can predict subsequent treatment response to Y-90 radioembolization in patients with hepatocellular carcinoma (HCC).

Study Aims and Objectives:

1. Assess the detection rate of CTC and cfDNA-based mutations and the distribution of molecular features of HCC prior to Y90 across BCLC A-C stages.
2. Determine CTC and cfDNA predictors at baseline that predict Y90 treatment response at 6-9 months.
3. Determine temporal changes in CTC and cfDNA mutations from baseline over 6-9 month course post Y90.
4. Determine if CTC mean distribution, sCTCDNA, and/or cfDNA mutational dynamic changes are predictive of treatment response at 6-9 months.
5. Assess radiomic and liquid biopsy signatures associated with outcome
6. Compare predictive outcome models using liquid biopsy data, imaging data, or a combination (multiomic data)

Inclusion Criteria:

1. Age > or = 18 years
2. HCC confirmed on imaging, BCLC stage 0, A, B, or C
3. Transarterial Y90 radioembolization approved by multidisciplinary tumor board -

Exclusion Criteria:

1. Not eligible for Y90 procedure
2. Prior surgery or ablation on indicated tumors
3. Patient unable to complete the follow up visits required for clinical care or research -

Patients at VAPAHCS with HCC