| Summary: | Purpose: to evaluate the clinical impact of a protocol for the image-guided percutaneous microwave ablation (MWA) of hepatocellular carcinoma (HCC) that includes cone-beam computed tomography (CBCT), fusion imaging and ablation volume prediction in patients with hepatocellular carcinoma unsuitable for standard ultrasound (US) guidance. Materials and Methods: this study included all patients with HCC treated with MWA between January 2021 and June 2022 in a tertiary institution. Patients were divided into two groups: Group A, treated following the protocol, and Group B, treated with standard ultrasound (US) guidance. Follow-up images were reviewed to assess residual disease (RD), local tumor progression (LTP) and intrahepatic distant recurrence (IDR). Ablation response at 1 month was also evaluated according to mRECIST. Baseline variables and outcomes were compared between the groups. For 1-month RD, propensity score weighting (PSW) was performed. Results: 80 consecutive patients with 101 HCCs treated with MWA were divided into two groups. Group A had 41 HCCs in 37 patients, and Group B had 60 HCCs in 43 patients. Among all baseline variables, the groups differed regarding their age (mean of 72 years in Group A and 64 years in Group B, respectively), new vs. residual tumor rates (48% Group A vs. 25% Group B, <i>p</i> < 0.05) and number of subcapsular tumors (56.7% Group B vs. 31.7% Group A, <i>p</i> < 0.05) and perivascular tumors (51.7% Group B vs. 17.1% Group A, <i>p</i> < 0.05). The protocol led to repositioning the antenna in 49% of cases. There was a significant difference in 1-month local response between the groups measured as the RD rate and mRECIST outcomes. LTP rates at 3 and 6 months, and IDR rates at 1, 3 and 6 months, showed no significant differences. Among all variables, logistic regression after PSW demonstrated a protective effect of the protocol against 1-month RD. Conclusions: The use of CBCT, fusion imaging and ablation volume prediction during percutaneous MWA of HCCs provided a better 1-month tumor local control. Further studies with a larger population and longer follow-up are needed.
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