Proton Therapy and Bevacizumab for Primary Liver Tumors

Inclusion Criteria:

* Cytologic or histologic proof of primary liver cancer (hepatocellular carcinoma or cholangiocarcinoma). Patients with non-metastatic, unresectable disease are eligible. Patients with positive margins after surgical resection are eligible. Metastasis is defined as unequivocal evidence of extrahepatic disease based on CT imaging, excluding nodal disease.
* Tumors must not be greater than 10cm (small satellite lesions around a larger lesion are allowed), all of which can be encompassed in a radiation treatment field (as assessed by the radiation oncologist).
* Prior chemotherapy, transarterial chemoembolization and radiofrequency ablation are permitted. A minimum of four weeks must have elapsed between prior treatment and planned protocol therapy.
* Prior liver resection is permitted as long as the interval between surgery and enrollment is at least 4 weeks.
* Karnofsky performance status \>/= 70 are eligible.
* There is no age restriction.
* Absolute granulocyte count \>/= 1,500 cells/mm3, hemoglobin \>/= 8 gm/dL and platelet count \>/= 80,000 cells/mm3.
* Serum creatinine \</= 1.5 mg/dl.
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \</= 3 times the upper limit of normal. Serum bilirubin \</= 5mg/dL prior to the start of therapy.
* A signed study-specific consent form, which is attached to this protocol.

Exclusion Criteria:

* Child-Pugh class C cirrhosis.
* Gross ascites seen on CT that precludes accurate targeting of the tumor with radiation therapy
* Proteinuria at screening as demonstrated by either Urine protein:creatinine (UPC) ratio \> 1.0 at screening OR Urine dipstick for proteinuria \> 2+ (patients discovered to have \> 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate \< 1g of protein in 24 hours to be eligible).
* Patients currently receiving anticoagulation treatment with coumadin, low molecular weight heparin or IV heparin. Evidence of bleeding diathesis or coagulopathy. Anticoagulation for line maintenance is permitted.
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of the study; fine needle aspirations or core biopsies within 7 days prior to Day 0.
* Serious, nonhealing wound, ulcer, or bone fracture.
* Clinically significant cardiac disease (e.g., uncontrolled hypertension \[blood pressure of \>150/100 mmHg on medication\], history of myocardial infarction within 6 months, unstable angina), New York Heart Association (NYHA) Class II or greater congestive heart failure, unstable symptomatic arrhythmia requiring medication (subjects with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia are eligible), or Class II or greater peripheral vascular disease.
* History of aneurysms, strokes, transient ischemic attacks, and arteriovenous malformations within 6 months.
* Prior unanticipated severe reaction to bevacizumab.
* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0
* Patients who have had an organ allograft.
* Pregnant women are excluded from this study; women of childbearing potential must agree to practice adequate contraception (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) and to refrain from breast feeding, as specified in the informed consent. Women of child-bearing potential are defined as those women who have not had surgical sterilization or been menopausal for 12 consecutive months.
* Male patients must agree not to father a child and must agree to use a condom.
* Prior radiation therapy to an upper abdominal or lower thoracic field that could overlap with the proposed treatment field.
* Serious concomitant medical or psychiatric disorders that place the patient at high risk for non-compliance with or morbidity due to protocol therapy.
* Patients with a history of hypertension must be well-controlled (\</= 140/90 mmHg on a stable regimen of antihypertensive therapy)