Neoadjuvant intensity modulated radiotherapy for a single and small (≤5 cm) hepatitis B virus-related hepatocellular carcinoma predicted to have high risks of microvascular invasion: a randomized clinical trial

BACKGROUND: The presence of microvascular invasion (MVI) significantly impairs postoperative long-term survival of patients with hepatocellular carcinoma (HCC). The role of neoadjuvant radiotherapy (RT) in treating patients with an early-stage HCC predicted to have high risks of MVI remains to be explored. MATERIALS AND METHODS: Consecutive patients with a resectable single and small (≤5 cm) hepatitis B virus-related HCC predicted to have high risks of MVI were randomized 1:1 to receive either neoadjuvant intensity modulated radiation therapy (18 Gy with fractionated doses of 3 Gy) followed by surgery 4 weeks later or upfront surgery. The primary endpoint was disease-free survival (DFS). The secondary outcomes included overall survival (OS), objective response rate, RT-related toxicity and surgical complications. RESULTS: There were 30 patients randomized to each of the two groups. In the neoadjuvant RT group, three patients violated the study protocol, with two having upfront hepatectomy and one radiofrequency ablation after RT. The objective response rate after RT was 25.0% (7/28), but 2 patients suffered from grade 3 liver toxicity. The median follow-up was 68 months (interquartile range, 58–70 months) in the neoadjuvant RT group, and 68 months (interquartile range, 62–75 months) in the upfront surgery group. On intention-to-treat analysis, the median DFS and median OS were not reached in both the 2 arms. The 1-year, 2-year, 3-year and 5-year DFS rates for the neoadjuvant RT group were 86.7%, 76.7%, 60.0% and 56.3%, versus 90.0%, 66.7%, 52.8% and 45.7% in the upfront surgery group (P=0.448), respectively. The corresponding OS rates were 96.7%, 86.7%, 83.3% and 72.7%, versus 100.0%, 93.3%, 79.6% and 60.7% (P = 0.399). CONCLUSION AND RELEVANCE: For patients with a resectable single and small hepatitis B virus-related HCC predicted to have high risks of MVI, neoadjuvant RT gave a promising response rate with a mild toxicity. Nevertheless, the neoadjuvant RT yielded similar long-term DFS and OS rates compared with patients who underwent upfront surgery.