Purpose: The purpose of this study was to evaluate the usefulness of the combination guidance of contrast-enhanced US (CEUS) and fusion imaging in radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) with poor conspicuity on B-mode US and CEUS/fusion imaging. Materials and Methods: We conducted a retrospective cohort study, which included 356 patients with 556 HCCs that were inconspicuous on B-mode US. A total of 192 patients with 344 HCCs, 123 patients with 155 HCCs, and 37 patients with 57 HCCs underwent RFA under CEUS guidance, fusion imaging guidance, and the combination of CEUS and fusion imaging guidance. Results: The average number of treatment sessions was 1.1 (range: 1-2) in the CEUS guidance group, 1.1 (range: 1-2) in the fusion imaging guidance group, and 1.1 (range: 1-3) in the combination of CEUS and fusion imaging guidance group. Treatment analysis did not reveal significantly more RFA treatment sessions in the combination guidance group than in the other groups (p = 0.97, Student's t test). During the follow-up period (1.1-85.3 months, mean ± SD, 43.2 ± 59.5), the 3-year local tumor progression rates were 4.9, 7.2, and 5.9% in the CEUS guidance group, the fusion imaging guidance group, and the combination guidance group, respectively (p = 0.84, log-rank test). Conclusion: In spite of selection bias, session frequency and local tumor progression were not different under the combination guidance with CEUS and fusion imaging in RFA. The combination of fusion imaging and CEUS guidance in RFA therapy is an effective treatment for HCC with poor conspicuity on B-mode US and CEUS/fusion imaging.

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