Radiation Therapy With Protons or Photons in Treating Patients With Liver Cancer

Inclusion Criteria:

• Pathologically (histologically or cytologically) or radiographically-proven (basedon the American Association for the Study of Liver Diseases [AALSD] criteria)unresectable or locally recurrent hepatocellular cancer prior to registration

• Appropriate stage for study entry based on the following diagnostic workup:

• All patients must have computed tomography (CT) scan chest/abdomen/pelvis withmultiphasic liver CT scan prior to registration; if CT contrast iscontraindicated, CT chest without contrast and magnetic resonance imaging (MRI)of abdomen is permitted

• Participants must have measurable disease at study entry, defined as at leastone lesion that can be accurately measured in at least one dimension (longestdiameter to be recorded) as > 2 cm with conventional techniques or as > 1 cmwith spiral CT scan

• Patient must have 3 or fewer single or multinodular tumors; for patients with asingle lesion, lesion must be 15 cm or less in greatest dimension; for patientswith two lesions, no lesion may be greater than 10 cm in greatest dimension;for patients with three lesions, no lesion may be greater than 6 cm in greatestdimension; portal vein involvement or thrombosis combined with a single lesionthat is >= 1 cm and =< 15 cm in greatest dimension is allowed

• Age >= 18

• Zubrod performance status 0-1 within 30 days prior to registration

• Negative urine or serum pregnancy test for women of childbearing potential within 7days prior to study entry

• Absolute neutrophil count (ANC) >= 1,000 cells/mm^3

• Platelets >= 50,000 cells/mm^3

• Hemoglobin >= 9.0 g/dl; (Note: The use of transfusion or other intervention toachieve hemoglobin [Hgb] >= 9.0 g/dl is acceptable)

• Total bilirubin < 4 x institutional upper limit of normal (ULN)

• Transaminases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) < 6 x institutional ULN

• Albumin >= 2.5 g/dl

• Creatinine < 2 mg/dl

• Prior chemotherapy, targeted biological therapy (e.g. sorafenib), surgery,transarterial chemoembolization (TACE), ablation for present disease is acceptable

• Must have Child-Turcotte-Pugh (CTP) A or B7

• The patient or a legally authorized representative must provide study-specificinformed consent prior to study registration

Exclusion Criteria:

• PRIOR TO STEP ONE REGISTRATION:

• Definitive clinical or radiologic documentation of extrahepatic tumor, defined asextrahepatic metastases or malignant nodes (that enhance with typical features ofHCC) > 3.0 cm, in sum of maximal diameters (e.g. presence of one 3.4 cm metastaticlymph node or two 2 cm lung lesions); note that benign non-enhancing periportallymphadenopathy is not unusual in the presence of hepatitis and is permitted, evenif the sum of enlarged nodes is > 2.0 cm

• Uncontrolled prior invasive malignancy, excluding the current diagnosis

• Systemic chemotherapy for the study cancer < 2 weeks prior to registration

• Pregnancy or women of childbearing potential and men who are sexually active and notwilling/able to use medically acceptable forms of contraception; this exclusion isnecessary because the treatment involved in this study may be significantlyteratogenic

• HIV positive with CD4 count < 200 cells/microliter; note that patients who are humanimmunodeficiency virus (HIV) positive are eligible, provided they are undertreatment with highly active antiretroviral therapy (HAART) and have a CD4 count >= 200 cells/microliter prior to registration; note also that HIV testing is notrequired for eligibility for this protocol; this exclusion criterion is necessarybecause the treatments involved in this protocol may be significantlyimmunosuppressive

• Prior radiotherapy to the region of the study cancer that would result in overlap ofradiation therapy fields (to include Y90)

• Prior liver transplant

• PRIOR TO STEP TWO RANDOMIZATION:

• Unable to obtain confirmation of payment coverage (insurance or other) for eitherpossible treatment