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Background and Aims  Surgical resection is the primary treatment for HCC; however, it is associated with a high rate of recurrence and death. We conducted this phase 2 study to investigate the efficacy and safety of postoperative intensity‐modulated radiotherapy (IMRT) for HCC after narrow‐margin hepatectomy.    Approach and Results  We designed a single‐arm, prospective phase 2 trial to evaluate overall survival (OS), disease‐free survival (DFS), recurrence patterns, and toxicity in patients receiving adjuvant radiotherapy. The eligibility criteria included the following: pathological diagnosis of HCC after hepatectomy, with narrow pathological margins (< 1 cm); age > 18 years; and Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients received IMRT within 4‐6 weeks after surgical resection. This trial was registered at ClinicalTrials.gov (NCT01456156). Between 2008 and 2016, a total of 76 eligible patients who underwent narrow‐margin resection were enrolled. The median follow‐up duration was 70 months; the 3‐year OS and DFS rates were 88.2% and 68.1%, respectively; and the 5‐year OS and DFS rates were 72.2% and 51.6%, respectively. Intrahepatic recurrence was the primary recurrence pattern. No marginal recurrence was found. Intrahepatic, extrahepatic, and combined recurrences at the first relapse were found in 33, 5, and 1 patient, respectively. The most common radiation‐related grade‐3 toxicities were leukopenia (7.9%), elevated alanine aminotransferase (3.9%) and aspartate aminotransferase (2.6%) levels, and thrombocytopenia (1.3%). Classical or nonclassical radiation‐induced liver disease was not noted.    Conclusions  Adjuvant radiotherapy is an effective, well‐tolerated, and promising adjuvant regimen in patients with HCC who have undergone narrow‐margin hepatectomy. Our trial provides evidence and a rationale for planning a future phase 3 trial.

Phase 2 Study of Adjuvant Radiotherapy Following Narrow‐Margin Hepatectomy in Patients With HCC