Y-90 Versus SBRT for Inoperable HCC

Inclusion Criteria:

* Ability to understand and the willingness to sign a written informed consent document.
* Age \>= 18 years at time of informed consent. Both men and women and members of all races and ethnic groups will be included.
* Patient with non-metastatic hepatocellular carcinoma (HCC) including lesion(s) amenable to definitive therapy with either SBRT or Y-90 segmentectomy, limited to =\< 2 liver segments, as agreed upon by the multidisciplinary tumor board consensus.
* Patient not otherwise optimal candidates for resection or thermal ablation, as agreed upon by the multidisciplinary tumor board.
* Have a Child-Pugh criteria (CP) score B7 or better.
* Eastern Clinical Oncology Group (ECOG) performance status =\< 1, or Karnofsky performance scale \> 70.
* No other prior invasive malignancy is allowed except for the following: adequately treated basal or squamous cell skin cancer, in situ breast or cervical cancer. Stage I or II invasive cancer treated with a curative intent without evidence of disease recurrence for at least five years.

Exclusion Criteria:

* Participant is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment.
* Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, serious or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events (AEs) or compromise the ability of the patient to give written informed consent.