Phase II Study of Short-course Carbon Ion Radiotherapy (52.8 GyE/4-fraction/1-week) for Hepatocellular Carcinoma

Background: We commenced clinical trials of carbon ion radiotherapy (CIRT)for hepatocellular carcinoma (HCC) in April 1995. The first phase I/II trial was conducted with 15-fraction/5-week regimen until March 1997. Following this, the second phase I/II trial was carried out to evaluate the short-course CIRT during the next 4 years. Based on its results, a phase II clinical trial was conducted from April 2001 to February 2003.Purpose: To evaluate the safety and efficacy of the short-course CIRT of 52.8 GyE/4-fraction/1-week for HCC.Patients and Methods: Eligibility criteria were as follows: biopsy-proven HCC; recurrent or residual tumor after other ineffective treatments or no indication for any other treatment; no tumor thrombosis of the portal main branch; no other viable lesion outside the planning target volume; no prior radiotherapy for target tumors; hepatic disorder of Child-Pugh grade A or B; Karnofsky performance status of 60-100; no other active cancer; and digestive tract not in contact with clinical target volume. CIRT was administered in doses of 52.8 cobalt gray equivalent in 4 fractions for 1 week. Results: Forty-seven patients were enrolled. Because 3 of them were twice treated with the same regimen in this study, the number of objects for local control and survival analysis was 47 and 44, respectively. The survival period was calculated from the day of start of the first CIRT. The median age at therapy was 69 (46-84) years. All patients had chronic liver diseases of Child-Pugh grade A in 37, B in 10 (liver cirrhosis: 40, chronic hepatitis: 7). Twenty patients (43%) had intrahepatic recurrent lesions. The median tumor size was 3.7 (1.2-7.5) cm in diameter. During a median follow-up of 36 (24-46) months, no hepatic failure resulting from the therapy and no treatment-related death occurred. Incidence of grade 3 early hepatic toxicity according to NCI-CTC was 0, 11, 0, 2, and 13% in the serum-GPT, ALB, T.BIL, PT and ALP, essential valuables concerning hepatic function, respectively. No grade 4 toxicity occurred. No other grade 3 or worse adverse effect occurred. In 93% and 92% of patients, the Child-Pugh score did not increase by more than 1 point in the early and late phase, respectively. Local control and overall survival rates were 98%, 93%, and 95%, 66% at 1 and 3 years, respectively. Those at 3 years in the 27 patients initially treated with CIRT were 96% and 71%, respectively, that were comparable with those in the hepatic resection. Conclusion: Short-course CIRT of 52.8GyE/4-fraction/1-week for HCC seems to have a promising potential as a new, radical, and minimally invasive therapeutic option for HCC.56th Annual Meeting of the American Association for the Study of Liver Disease