Not feasible at this time.

This phase II trial tests whether Y-90 segmentectomy (internal radiation) versus stereotactic body radiation therapy (external radiation) is more optimal in treating inoperable liver cancer. Y-90 segmentectomy consists into very tiny radioactive glass beads that can be injected into the liver through the blood vessels supplying the liver. Stereotactic body radiation therapy uses special equipment to position a patient and deliver external radiation to tumors with high precision. This study many help doctors determine which treatment, Y-90 segmentectomy or SBRT, works better in treating liver cancer.

PRIMARY OBJECTIVE:

I. Determine feasibility of trial enrollment (enrollment date).

SECONDARY OBJECTIVE:

I. To assess differences in overall survival, local control, time to intrahepatic progression, time to next treatment, rate of liver transplant, toxicity, and patient reported complications and quality of life.

EXPLORATORY OBJECTIVE:

I. Compare cumulative cost of treatment-related medical care at 13 months.

OUTLINE: Patients will be randomized in 1 of 2 arms.

Arm I: Patients undergo SBRT every other day for a total of 5 days over 2 weeks.

Arm II: Patients receive Y-90 radioembolization via injection on day 1.

After completion of study, patients are followed up at 2, 4, and 12 weeks and then every 3 months for 13 months.

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.