In this study the investigators will be studying the effects of proton beam radiation therapy. This is a very accurate kind of treatment that has been shown to affect less normal tissue than a photon radiation beam. The accuracy allows the investigators to more safely increase the amount of radiation delivered to eliminate cancer. This accuracy will potentially reduce side effects that participants would normally experience using photon radiation therapy. The purpose of this study is to determine if radiation using proton beam therapy will kill the cancer cells in the participants liver.

• Participants will receive treatment as an outpatient in the Francis H. Burr Proton Center at the Massachusetts General Hospital, the MD Anderson Proton Therapy Center or the Roberts Proton Therapy Center at the University of Pennsylvania.
• Not everyone who participates in this study will be receiving the same dose of radiation. The dose received will be determined by the location of the tumor(s) within the liver.
• Proton Beam radiation therapy to the liver will be given once a day, 5 days a week (Monday-Friday), for 2 weeks.
• The following procedures will be performed once a week during treatment on days 1, 8 and 15, as well as on the last day of radiation: physical examination and blood tests.

Inclusion Criteria:

• Biopsy proven unresectable or locally recurrent hepatocellular cancer or intrahepatic cholangiocarcinoma. Patients with a single lesion must be 12cm or less in greatest dimension. For patients with two lesions, no lesion may be greater than 10cm in greatest dimension. For patients with three lesions, no lesion may be greater than 6cm in greatest dimension. Patients may have single or multinodular tumors (up to 3). There must be no evidence of extrahepatic tumor. Portal vein involvement or thrombosis is allowed.
• Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as 20mm or greater with conventional techniques or as 10mm or greater with spiral CT scan.
• Patients may have had prior chemotherapy, targeted biological therapy, surgery, transarterial chemoembolization (TACE), radiofrequency ablation, or cryosurgery for their disease as long as it is greater than 4 weeks from first protocol radiation treatment (6 weeks for nitrosoureas or mitomycin C). Patients may not have had prior radiation to the affected area.
• 18 years of age or older
• Expected survival must be greater than three months
• ECOG Performance Status of 0, 1 or 2
• Normal organ and marrow function as outlined in the protocol
• If patient has underlying cirrhosis, only Child-Pugh classification Group A or Group B patients should be included in this study.
• Patients must be either surgically sterile or post-menopausal. Male and female patients of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of the study participation.
• Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin

Exclusion Criteria:

• Women who are pregnant or lactating
• Patients with evidence of non-hepatic metastatic disease
• Local conditions or systemic illnesses which would reduce the local tolerance to radiation treatment, such as serious local injuries, active collagen vascular disease, etc.
• Prior liver directed radiation treatment
• Patients may have no serious medical illness, which may limit survival to less than 3 months
• Patients may have no serious psychiatric illness/social situations which would limit compliance with study requirements
• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Patients may not be receiving any other study agents
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia.

Adverse event information was collected from the start of treatment until 30 days after the last study visit. Radiation was delivered in 15 fractions Monday through Friday over a period of three weeks. Follow-up visits occurred at 1, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, and 60 months post treatment. Median follow-up was 19.5 months.

Adverse events were assessed with the use of regularly scheduled visits which involved physical exams, CT and/or MRI scans, laboratory tests, and patient self reporting. If an adverse event did not match any of the existing CTCAE 3 terms, it was noted as being 'other'. Adverse events noted as being 'other' were only grouped together by organ system due to incomplete data about what specific adverse event was being recorded as 'other'.