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.

Eligibility Criteria:
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)