194 hepatocellular cancers treated by radiation and chemotherapy combinations: toxicity and response: a Radiation Therapy Oncology Group Study.

Hepatocellular carcinoma is known to have a doubling time of approximately 41 days. This rapid cell division suggested that hyperfractionated radiation and chemotherapy might add an advantage in gaining remission of this malignancy. One hundred and thirty-five patients (70% with metastasis and/or previous treatment) were prospectively treated with single daily fractions to the liver (3.0 Gy external beam radiation, total dose 21.0 Gy), and chemotherapy for hepatocellular carcinoma. The low dose chemotherapy used in conjunction with the radiation was 2 hr before treatment on days 1, 3, 5, and 7 and consisted of Adriamycin, 15 mg IV and 5-FU, 500 mg IV. These patients were compared to a second group of 59 patients (80% with metastases and/or previous treatment) treated using the same chemotherapy regimen but using hyperfractionated whole liver external beam irradiation (1.2 Gy twice daily, 4 hr between treatments, 5 days per week to 24.0 Gy, 10 MV photons). Response was determined by CT scan tumor volumetric analysis. The response rate for the single daily fraction patient group was 22% and for the new hyperfractionated group, 18% (p = 0.68). Toxicity was evaluated by RTOG criteria. The grade 4 hematologic toxicity noted in the daily fraction patient group was 6%. Among 59 patients treated with the hyperfractionated liver irradiation, 2% experienced grade 4 hematologic toxicity. Esophagitis occurred in 1% of patients in the standard fractionation group and 19% in the hyperfractionated group (p = 0.0001). Grade 1-4 thrombocytopenia occurred in 49% of patients in the conventional group and 68% in the hyperfractionated group (p = 0.03). Normal liver volume changes with treatment were measured with CT scan tumor volumetric analysis. The hyperfractionated group experienced a median of 11 cc increase in liver volume and the conventional group a 46 cc decrease, but the difference was not significant. Hyperfractionated radiation did not demonstrate a significant benefit over standard daily radiation, but acute toxicity appeared to be higher.