Survival benefit of higher fraction dose delivered by three-dimensional conformal radiotherapy in hepatocellular carcinoma smaller than 10 cm in size

Objective: Even in early-stage hepatocellular carcinoma (HCC), patients are often ineligible for surgical resection, transplantation, or local ablation due to advanced cirrhosis, donor shortage, or difficult tumor location. To compare the safety and efficacy of different fractions on the survival of patients with tumors smaller than 10 cm in size, hepatocellular carcinoma (HCC) patients ineligible for curative therapies were treated with three-dimensional conformal radiotherapy (3DCRT). Methods: A total of 198 HCC patients who had tumors smaller than 10 cm and were not eligible for surgical resection or local ablation therapy received 3DCRT. Participants were separated into two groups. The treatment for Group A (n = 111) was a median total dose of 53 Gy with a fraction of 2.5-4.9 Gy given three times a week, while treatment for Group B (n=87) was a median total dose of 52 Gy with a fraction of 5.0-7.0 Gy given three times a week. Propensity score matching (PSM) was conducted, and after the PSM, 81 pairs of patients arose. The Kaplan-Meier method was adopted to analyze overall survival; multivariate analysis was applied to identify the prognostic factors of survival. Results: The median follow-up time was 19.7 months (ranging from 1 to 186 months). The median survival for Group A patients versus Group B patients was 14.4 versus 24.8 months (P=0.003), respectively. The overall survival rates at 1, 3, and 5 years were 57.7%, 30.6%, and 18.9% for Group A patients and 73.6%, 43.7%, and 33.3% for Group B patients, respectively (P=0.009). In addition, the results in the PSM model appeared to be similar between the two groups. After PSM, the association between four independent prognostic factors and worse overall survival was discovered as follows: tumor size (>5 cm), Child-Pugh class B, portal vein tumor thrombosis, and fraction of 2.5-4.9 Gy/fx. The two groups also shared similar toxicities. Conclusions: Higher fraction dose radiotherapy delivered by 3DCRT was effective, as it offered a survival benefit without aggravating the toxicities in patients with small- to medium-sized HCC tumors who were ineligible for curative therapies.