Stereotactic Body Proton Radiotherapy for the Treatment of Liver Cancer

Inclusion Criteria:

* Age \>= 18 years
* Radiologically presumed or histologically proven, newly diagnosed or recurrent, hepatocellular carcinoma
* Clinical stage T0-T4N0M0 (American Joint Committee on Cancer \[AJCC\] 8th edition).

  * One to three discrete Liver Reporting and Data System-5 (LIRADS-5) lesions that can be encompassed within a single radiation treatment plan
  * Patients treated with external beam radiation as a bridge to transplant are allowed
  * Minimum single lesion size \>= 1 cm, maximum cumulative diameter =\< 15 cm
  * Vascular involvement (including portal vein, inferior vena cava \[IVC\] and/or hepatic vein) is allowed
* Target lesion must be amenable to a SBRT regimen utilizing proton beam therapy (i.e. SBPT)
* Prior local liver treatment including surgery, percutaneous ablation, transarterial bland or chemoembolization (TACE), or Y-90 radioembolization is allowed if completed at least 6 weeks prior to treatment start date
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 2
* Life expectance \>= 3 months based on medical comorbidities, tumor extent and other clinical factors as determined by treating physician
* Child Pugh score of A or B7
* Absolute neutrophil count (ANC) \>= 1000 cells/mm\^3 (within 45 days of study entry)
* Platelets (Plt) \>= 30,000 cells/mm\^3 (the use of transfusion or other intervention to achieve the minimum platelet level is allowed) (within 45 days of study entry)
* Hemoglobin (Hgb) \>= 8.0 g/dL (the use of transfusion or other intervention to achieve the minimum hemoglobin level is allowed) (within 45 days of study entry)
* Total bilirubin \< 2 mg/dL (within 45 days of study entry)
* Able to and provides Institutional Review Board (IRB) approved study specific written informed consent
* Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
* Enrollment on a second independent protocol is allowed if the second protocol intervention will not significantly affect results of the current protocol as determined by the study investigators

Exclusion Criteria:

* Medical contraindication to receipt of radiotherapy
* Severe active co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
* Uncontrolled concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or providing informed consent
* Active systemic lupus or scleroderma
* Women of childbearing potential who are sexually active and not willing/able to use medically acceptable forms of contraception
* Prior receipt of external beam radiation to the current active disease site or if additional radiotherapy to the current site would be unsafe as determined by the treating radiation oncologist
* More than 3 LIRADS-5 lesions or disease extent such that organ at risk constraints cannot be met
* Tumor extension into common or main branch biliary duct or adjacent organs including stomach, small or large bowel
* Extrahepatic metastases or lymph node involvement
* History of other malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 1 year prior to study entry
* Patient is unable to undergo intravenous contrast enhanced liver imaging (either computed tomography \[CT\] or magnetic resonance imaging \[MRI\]) based on clinical imaging protocols established at the treating institution