Radiation Therapy in Treating Patients With Liver Cancer That Cannot Be Removed by Surgery
Radiation Therapy in Treating Patients With Liver Cancer That Cannot Be Removed by Surgery
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. This may be an
 effective treatment for liver cancer.

 PURPOSE: This phase I/II trial is studying the side effects and best dose of external-beam
 radiation therapy in treating patients with liver cancer that cannot be removed by surgery.
OBJECTIVES:

 -  To assess the feasibility and safety of radiotherapy (RT) in patients with
 hepatocellular carcinoma. (Phase I)

 -  To assess the safety and efficacy of RT in these patients. (Phase II)

 -  To generate reproducible peptide patterns of the serum proteome or specific serum sub
 proteomes in these patients.

 -  To assess changes in the proteome or sub proteome patterns after RT in these patients.

 -  To detect peptides that discriminate between before and after RT in these patients.

 -  To identify these discriminating peptides in these patients.

 OUTLINE: This is a multicenter, phase I dose-escalation study followed by a phase II study.

 Patients undergo radiotherapy (RT) once daily, five days a week, for 6 weeks.
 Intensity-modulated, 3-dimensional conformal, or fractionated stereotactic RT may be used.

 After completion of study therapy, patients in the phase I portion are followed for 1 year
 and patients in the phase II portion are followed for 3 years.
DISEASE CHARACTERISTICS:

 -  Histologically, cytologically, or radiologically confirmed hepatocellular carcinoma

 -  Clinical stage T2-4, N0-1, M0 (stage II, IIIA, IIIB, IIIC) OR unresectable T1,
 N0-1, M0 (stage I) disease

 -  M1 disease allowed in phase I if at least 90% of the tumor load (volume) is
 in the liver

 -  Measurable disease (at least one liver lesion that can be measured in at least one
 dimension as ≥ 10 mm in multislice CT scan/MRI)

 -  Volumetry of liver tumor and residual liver tissue: residual liver volume (= total
 liver volume - gross tumor volume) has to be ≥ 800 mL and ≥ 40% of total liver volume

 -  No operable disease (with curative intent or planned liver transplantation)

 -  No presence of clinical ascites

 PATIENT CHARACTERISTICS:

 -  WHO performance status 0-2

 -  Cirrhosis Child-Pugh class A or B (Child-Pugh score of ≤ 9)

 -  Hemoglobin ≥ 100 g/L

 -  ANC ≥ 1,200/mm³

 -  Platelet count ≥ 50,000/mm³

 -  ALT and AST ≤ 7 times upper limit of normal (ULN)

 -  AP ≤ 10 times ULN

 -  Bilirubin ≤ 50 μmol/L

 -  INR ≤ 2

 -  Creatinine clearance ≥ 50 mL/min

 -  Functional left kidney (scintigraphy mandatory for phase I, phase II only if
 indicated)

 -  Lipase ≤ 2 times ULN (phase I only)

 -  Able to tolerate proton-pump inhibitors or H2 antagonists during radiation therapy

 -  Not pregnant

 -  Negative pregnancy test

 -  Fertile patients must use effective contraception during and for 4 months after
 completion of study therapy

 -  No prior malignancy allowed, except for the following:

 -  Adequately treated cervical carcinoma in situ

 -  Adequately treated localized nonmelanoma skin cancer

 -  Any other malignancy from which patient has been disease-free for 5 years

 -  No presence of medically uncontrolled encephalopathy

 -  No myocardial infarction within the past 6 months

 -  No esophageal varices ≥ grade 3, with red signs, or bleeding within the past 3 months

 -  No symptoms of colitis, enteritis, esophagitis, fistula, gastritis, ileus, necrosis,
 perforation, stricture, or ulcer

 -  No severe anorexia, constipation, dehydration, diarrhea, or vomiting

 -  No serious underlying medical condition that, in the opinion in the investigator,
 would preclude study participation (e.g., active autoimmune disease or uncontrolled
 diabetes)

 -  Portal vein thrombosis allowed

 -  No psychiatric disorder precluding understanding of information on study related
 topics or giving informed consent

 -  No nutritional intake < 1500 calories per day (corrected)

 -  No weight loss ≥ 15 % within the past 3 months

 PRIOR CONCURRENT THERAPY:

 -  At least 8 weeks since prior transarterial chemoembolization (TACE), radiofrequency
 ablation, or radiotherapy (RT) unless progressive disease was documented after this
 therapy

 -  At least 21 days since prior and no other concurrent treatment with experimental drugs

 -  At least 21 days since prior and no other concurrent treatment on another clinical
 trial

 -  At least 21 days since prior and no other concurrent anticancer therapy

 -  No prior RT to the abdomen or caudal chest

 -  Prior RT to pelvis allowed

 -  Prior RT to chest must be above D5 vertebra

 -  Portal vein embolization ligation or pre-RT TACE allowed

 -  No concurrent treatment with steroids or non-steroidal anti-inflammatory drugs during
 RT (proton-pump inhibitor allowed)