Dose escalation in radiotherapy for incomplete transarterial chemoembolization of hepatocellular carcinoma

Purpose: To investigate the efficacy of radiation dose escalation in patients with hepatocellular carcinoma (HCC) after incomplete transarterial chemoembolization (TACE). Methods: This study evaluated retrospective data of 323 HCC patients who received radiotherapy after incomplete TACE from 2001–2016. Radiation dose in biologically effective dose (BED) (α/β = 10) was categorized as <72 Gy (261 patients) and ≥72 Gy (62 patients). Simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) was used significantly more frequently in the high-dose group (64.5% vs. 12.9%; P < 0.001). Local failure-free rate (LFFR), progression-free rate (PFR), and toxicities were compared between the two groups. Additionally, propensity score matching was performed. Results: Median follow-up time for patients who were alive at the time of analysis was 47 months (range 18–189 months). Median overall survival after radiotherapy was 14 months. In multivariate analysis, BED ≥72 Gy was an independent predictor of favorable LFFR (hazard ratio [HR] 0.32; 95% confidence interval [CI] 0.14–0.72; P = 0.006) and PFR (HR 0.67; 95% CI 0.45–0.98; P = 0.04). In the propensity score-matched cohort (62 pairs), 1‑year LFFR (94% vs. 81%; P = 0.002), and 1‑year PFR (49% vs. 42%; P = 0.01) were significantly higher in the high-dose group. Treatment-related toxicities were comparable between the high-dose and low-dose groups (classic radiation-induced liver disease: 5.3% [3/57] vs. 13.8% [29/210], P = 0.08; grade 2–4 gastrointestinal bleeding: 3.2% [2/62] vs. 7.3% [19/261], P = 0.39). Conclusion: Radiation dose with BED ≥72 Gy improved LFFR and PFR without increasing toxicity. In radiotherapy for incomplete TACE of HCC, dose escalation using SIB-IMRT should be actively considered to improve oncologic outcome.