Hepatocellular Carcinoma: Preliminary Results of the First Prospective Study on Short-Course Carbon-Ion Radiotherapy

Purpose: To evaluate the toxicity and anti-tumor effect of short-course carbon-ion radiotherapy for hepatocellular carcinoma (HCC) within a phase I and II clinical trial. Patients and Methods: Eighty-six lesions of histologically documented HCC associated with chronic liver disease were treated with short-course carbon-ion radiotherapy. Fifty-two (60%) lesions were recurrent (locally: 40, regionally: 12). Thirty-eight (44%) were Stage II disease, 35 (41%) Stage IIIA and 13 (15%) Stage IVA. Child-Pugh grade, an indicator of liver function, was A in 69, B in 14 and unevaluable in 3. Thirty-four lesions were treated with 12 fractions / 3 weeks, 24 with 8 fractions / 2 weeks, 28 with 4 fractions / 1 week. A dose escalation study was carried out by fraction dose increments of 10 % from 4.5 GyE for 12 fractions, resulting in total doses of 54.0 to 69.6 GyE in 12 fractions, 48.0 to 58.0 GyE in 8 fractions and 48.0 to 52.8 GyE in 4 fractions. Common Toxicity Criteria, RTOG/EORTC criteria and Child-Pugh score were used for evaluation of toxicity. Anti-tumor effect was evaluated by the best tumor response based on the WHO criteria, cumulative local control and survival rates. Results: During a mean follow-up of 42 (19-64) months, no severe adverse effects and no treatment-related deaths have occurred. Within 3 months after the start of therapy (early phase), no change or decrease in the Child-Pugh score was observed in 65% of the patients and an increase by only 1 point in 30%. Within 3 to 12 months after (late phase), similar observations were made in 52% and 26%, respectively. Only in the late phase, it increased by 3 points in three patients (5%), none of whom died of hepatic failure within 1 year after the first increase of the score. As to the best tumor response, the ratio of the number of CR and PR to that of all the lesions was 67/86 (78%). Local control rates were 92.8% and 87.3% at 1 and 2 to 3 years, respectively. Overall survival rates were 89%, 68% and 45% at 1, 2 and 3 year, respectively. Conclusion: The short-course carbon-ion radiotherapy for HCC preliminary proved to be safe and effective even for the patients with chronic liver diseases