Patient characteristics
The mean age of the patients was 65.6 ± 8.9 years (range, 47–79 years). Of the 53 patients, 17 (32.1%) were 65years old or younger, 23 (43.3%) were male, and 34 (64.1%) of the small HCC patients were associated with hepatitis B. In all of the patients, the mean target tumor size was 3.6 ± 0.9 (range, 2.6–4.9) cm, and 41 (77.4%) had tumors < 3 cm in diameter. Furthermore, 15 patients had tumors within 5mm of the hepatic dome, and the remaining 38 patients were beyond 5mm. Additionally, 35 (66.0%) patients were considered to be Child–Pugh A, while 18 (34.0%) were considered to be Child–Pugh B. The mean energy, ablation duration per tumor and the mean safety margin were 40.6 ± .9.7 kJ and 7.4 ± 2.5 min, respectively.
Safety
All patients underwent liver/kidney laboratory tests and alpha-fetoprotein (AFP) determination over the course of the first and fourth weeks post-procedure. The mean blood urea nitrogen (BUN) stayed within its normal range for the duration of 4 weeks after treatment. However, their mean total bilirubin (TBIL; P = 0.001) level saw a slight increase within the first week after the procedure, but was brought back to its normal levels by the fourth week. The mean albumin (ALB) was also largely back in its normal range after the fourth week. Additionally, combined treatment yielded a rapid decline in AFP levels (P<0.001), and was kept within an acceptable range after 4 weeks (Fig. 3).
Interventional-related complications
Most adverse events and complications were CTCAE grade 1 or 2 (mild symptoms, no or local/noninvasive intervention indicated), or interventional radiology society Grade A or B (no or nominal treatment, no consequences). Exceptions included six patients (11.3%) who had localized atelectasis of the lung parenchyma caused by localized thermal injury, three patients (5.7%) with perihepatic effusion requiring thoracic drainage, and one patient (1.9%) with pneumothorax who needed closed thoracic drainage and returned to stable within 3 days after treatment. None of the patients experienced life-threatening complications during or after treatment (Table 3).
LTP and OS
The survival analysis of CBCT-guided TACE sequential MWA for the treatment of small HCCs under the hepatic dome revealed a mean LTP of 44.406 months (95% CI: 39.429, 49.383) and mean OS of 55.157 months (95% CI: 52.559, 57.754) in the combination therapy. The 1-, 3- and 5-year LTP rates of the combination treatment were 92.5%, 69.6% and 34.5%, respectively (Fig. 4A); the 1-, 3- and 5-year OS rates were 100.0%, 88.4% and 70.2%, respectively (Fig. 4B). Univariate Cox proportional hazard regression indicated that Child-Pugh (A vs B), liver cirrhosis (YES vs NO) and the number of lesions (single vs 2–3 lesions) were not associated with longer LTP and OS (both P > 0.05). Additionally, both univariate and multivariate Cox regression revealed that the tumor diameter (< 3cm) and the distance to hepatic dome (⩾10mm, <5mm) did have a significant impact on the patient's LTP and OS and were related to better survival (Table 4).
Tumor diameter and the Distance to hepatic dome
The mean LTP for procedures with tumor diameter < 3cm was 50.622 months (95% CI: 46.183, 55.060), compared to 23.367 months (95% CI: 15.116, 31.617) for those with tumor diameter ≥ 3cm, <5cm (p = 0.000, log-rank test). The 1-, 3- and 5-year LTP-free survival rates for patients with tumor diameter < 3cm were 95.1%, 85.3% and 42.2%, respectively, and those with tumor diameter ≥ 3cm, <5cm were 83.3%, 8.3% and 8.3%, respectively (Fig. 5A). The mean OS was 58.342 months (95% CI: 56.732, 59.952) for those with tumor diameter < 3cm, and 44.650 months (95% CI: 37.492, 51.808) for those with tumor diameter ≥ 3cm, <5cm (p = 0.000, log-rank test). The 1-, 3- and 5-year OS rates for patients with tumor diameter < 3cm were 100.0%, 97.5% and 81.3%, respectively, and those for tumor diameter ≥ 3cm, <5cm were 100.0%, 58.3% and 33.3%, respectively (Fig. 5B). Regarding procedures with HCC distance to hepatic dome < 5mm, the mean LTP was 19.360 months (95% CI: 13.719, 57.263); for those with distance ≥ 10mm, <5mm, it was 54.350 months (95% CI: 51.437, 57.263) (p = 0.000, log-rank test). The 1-, 3- and 5-year LTP-free survival rates for patients with HCC distance to hepatic dome < 1mm were 73.3%, 6.7% and 0.0%, respectively; for those with distance ≥ 10mm, <5mm they were 100.0%, 91.9% and 48.3%, respectively (Fig. 6A). The mean OS for procedures with HCC distance to hepatic dome < 5mm was 44.962 months (95% CI: 38.906, 51.019), compared to 59.339 months (95% CI: 58.314, 60.365) for those with distance ≥ 10mm, <5mm (p = 0.000, log-rank test). The 1-, 3- and 5-year OS rates for patients with HCC distance to hepatic dome < 5mm were 100.0%, 60.0% and 17.8%, respectively, and those for distance ≥ 10mm, <5mm were 100.0%, 100.0% and 91.3%, respectively (Fig. 6B).