Optimal Timing of Radiotherapy after Incomplete Transarterial Chemoembolization for Barcelona Clinic Liver Cancer Stage B Hepatocellular Carcinoma

Abstract

Purpose: The optimal timing for radiotherapy (RT) after incomplete transarterial chemoembolization (TACE) remains unclear. This study investigated the optimal timing to initiate RT after incomplete TACE in patients with Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma.

Materials and methods: This study included 116 lesions in 104 patients who were treated with RT after TACE between 2001 and 2016. The time interval between the last TACE session and RT initiation was retrospectively analyzed. The optimal cut-off time interval that maximized the difference in local failure-free rates (LFFRs) was determined using maximally selected rank statistics.

Results: The median time interval was 26 days (range: 2-165 days). At a median follow-up of 18 months (range: 3-160 months), the median overall survival was 18 months. The optimal cut-off time interval appeared to be 5 weeks; using this cut-off, 65 and 39 patients were classified into early and late RT groups, respectively. Early RT group had a significantly poorer Child-Pugh class and higher alpha-fetoprotein levels compared to late RT group. Other characteristics, including tumor size (7 cm vs. 6 cm; p=0.144), were not significantly different between the groups. The 1-year LFFR was significantly higher in the early RT group than in the late RT group (94.6% vs. 70.8%; p=0.005). On multivariate analysis, early RT was identified as an independent predictor of favorable local failure-free survival (hazard ratio: 3.30, 95% confidence interval: 1.50-7.29; p=0.003).

Conclusion: The optimal timing for administering RT after incomplete TACE is within 5 weeks. Early administration of RT is associated with better local control.

Keywords: Carcinoma, hepatocellular; chemoembolization, therapeutic; radiotherapy.

Fig. 1. Local control probabilities at 1 year after radiotherapy as a function of time interval. The 95% confidence intervals have been plotted around the hazard ratios.

Fig. 2. LFFRs in the early and late radiotherapy groups using a cut-off time interval of (A) 2 weeks, (B) 3 weeks, (C) 4 weeks, (D) 5 weeks, (E) 7 weeks, and (F) 10 weeks. The difference in the LFFRs was the greatest using a cut-off time interval of 5 weeks. LFFR, local failure-free rate.

Fig. 3. (A) Local failure-free rate (LFFR), (B) outfield intrahepatic failure-free rate, (C) distant failure-free rate, and (D) overall survival (OS) rate in patients with cut-off time intervals of ≤5 weeks and >5 weeks.

Fig. 4. Local failure-free rates (LFFRs) in patients with cut-off time intervals of ≤5 weeks and >5 weeks after propensity score matching.