Two-fraction carbon ion radiotherapy for hepatocellular carcinoma: Preliminary results of a phase I/II clinical trial

Introduction: We reported that the 4-fraction/1-week carbon ion radiotherapy (CIRT) appeared to be safe and to have a promising potential as a new, radical, and minimally invasive therapeutic option for hepatocellular carcinoma (HCC) at the 2004 ASCO annual meeting. In order to evaluate the safety and efficacy of 2-fraction/2-day CIRT, the next clinical trial was conducted within a phase I/II study between April 2003 and August 2005.Methods:The subjects of this report were 32 patients with follow-up period of over 6 months. CIRT was administered in doses of 32.0 to 38.8 cobalt gray equivalent (GyE) in 2 fractions for 2 days in a step-wise dose-escalation study. The median age was 68 (53-80) years. All patients had chronic liver diseases of Child-Pugh grade A in 30 or B in 2. Nine patients had intrahepatic recurrent lesions. The median tumor size was 4.7 (2.0-6.0) cm in diameter. Because no evaluation criteria are available for general hepatic toxicity in the impaired liver, the General Hepatic Toxicity Criteria based on NCI-CTC was defined by the Liver Cancer Working Group.Results: During a median follow-up of 18 (6-28) months, no treatment-related death occurred. Grade 3 hepatic toxicity according to NCI-CTC was observed in one patient in serum-GOT, GPT, T.BIL, and prothrombin activity. Grade 3 general hepatic toxicity occurred in the same one. No other Grade 3 or worse adverse events have occurred. The overall tumor response rate was 91% (29/32) at 6 months after the therapy. One-year and 1.5-year local control rate was 96% (23/24) and 88% (15/17), respectively. One-year and 1.5-year overall survival rate was 100% (24/24) and 94% (17/18), respectively. There were preliminarily no differences in results between the 2-fraction and 4-fraction CIRT.Conclusion:Two-fraction CIRT for HCC appears preliminarily safe and effective as well as the 4-fraction one. However, further observation is needed because the follow-up period is too short to confirm its clinical efficacy.2006 Gastrointestinal Cancers Symposiu