Dose escalation by intensity modulated radiotherapy in liver-directed concurrent chemoradiotherapy for locally advanced BCLC stage C hepatocellular carcinoma

Abstract

Purpose: To evaluate the effects of dose escalation by intensity-modulated radiotherapy (IMRT) in liver-directed concurrent chemoradiotherapy for locally advanced Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma (BCLC-C HCC).

Materials and methods: During 2005-2016, 637 patients with BCLC-C HCC received RT with concurrent hepatic arterial 5-fluorouracil. Patients were divided into two groups according to the biologically effective doses for a tumor (α/β = 10 Gy): <72 Gy (536 patients) and ≥72 Gy (101 patients). In each group, 128/536 (24%) and 94/101 patients (93%) used IMRT, respectively.

Results: The median follow-up for patients alive at the time of analysis was 36 months (range, 6-159 months). For ≥72 Gy and <72 Gy groups, the median overall survival (OS) was 21 and 13 months, respectively (P = .002). The 1-year local failure-free survival (LFFS) were significantly higher in high-dose group (95% vs. 79%; P < .001). After propensity score matching, high-dose group still had significantly better 1-year OS (62% vs. 51%; P = .03) and 1-year LFFS (95% vs. 78%; P = .008). In the multivariate model, RT dose was an independent predictor of LFFS and OS. The surgical conversion rate was significantly higher in high-dose group (20% vs. 12%, P = .03), with substantially increased median OS among patients who underwent surgery (104 months vs. 11 months; P < .001). There were no significant differences in gastrointestinal bleeding or radiation-induced liver disease.

Conclusions: In liver-directed concurrent chemoradiotherapy, radiation dose escalation by IMRT increased LFFS and OS for locally advanced BCLC-C HCC. It also increased the conversion rate to curative resection, which was attributable to increased OS.

Keywords: Hepatic arterial infusion chemotherapy; Hepatocellular carcinoma; Intensity modulated radiotherapy; Radiation dose–response relationship.