Patients’ demographic and clinical characteristics
Of the 93 patients who underwent liver resection, 66 (60.2%) were male and 37 (39.8%) were female (Table 1). The median age at diagnosis was 11 (range, 1.7–87) months. The median AFP level was 76,131 (range, 10–1,881,360) ng/ml and the median tumour diameter was 10.6 (range, 5.1–15.8) cm. Fifty-seven (61.3%) patients had unifocal tumours, 7 (7.5%) had multifocal tumours, and 29 (31.2%) had tumours with unspecified focality.
Thirty-six (38.7%) patients had PRETEXT stage II tumours, 23 (24.7%) had stage III tumours, 3 (3.2%) had stage IV tumours, and 31 (33.3%) had tumours with unspecified PRETEXT stages. Seven (7.5%) patients had ruptured tumours. Nine patients (9.7%) had lung metastasis, three of them had single lung metastasis and 6 had multiple lung metastasis [1 (1.1%) had portal vein thrombosis concurrently]. Sixteen (17.2%) patients underwent primary liver resection. Twenty-two patients (23.7%) received cisplatin-based neoadjuvant chemotherapy and delayed surgery, 25 (26.9%) received preoperative TACE and delayed surgery, and 30 (32.3%) received a combination of cisplatin-based neoadjuvant chemotherapy, TACE, and delayed surgery. PRETEXT stage distribution of each treatment group was provided in supplementary table 1. The median number of treatment cycles was 2.5 (range, 1–8) for neoadjuvant chemotherapy and 2 (range, 1–7) for preoperative TACE. Forty patients had information regarding both PRETEXT and POST-TEXT stages available for analysis. Using the McNemar test, significant downstage was noted for the 12 cases with both PRETEXT and POST-TEXT stage information (p<0.001). Specifically, 2 cases from stage IV to III, 8 from stage III to II, and 2 from stage II to I. Furthermore, 10 patients with unspecified PRETEXT stage were confirmed to have POST-TEXT stages II (n=8) and I (n=2) tumours.
The detailed demographic and clinical characteristics of the excluded 42 patients were listed in supplementary table 2. The excluded patients were significantly higher in age, AFP value, and PRETEXT stage than the included 93 patients. Additionally, more patients of the excluded group had lung metastases and portal vein thrombosis. The overall outcomes of these patients were largely unknown, and these patients were excluded from further analysis.
Surgery and outcomes
Thirty-seven (39.8%) patients underwent hemihepatectomy, 17 (18.3%) underwent wedge resection, 13 (14.0%) underwent trisectionectomy, 9 (9.7%) underwent bisegmentectomy (left lateral sectionectomy), and 2 (2.2%) underwent central hepatectomy. Fifteen patients underwent liver resection at other institutions, but detailed surgical information was not available. Seventy-eight patients were operated in our institution, and surgical information was collected and analysed. The operative time, estimated volume of blood lost, and volume of red blood cells transfused were 290 (range, 100–510) minutes, 8.9 (range, 1.7-111.1) ml/kg, and 26.7 (range, 0–111.1) ml/kg, respectively. There were 24 (25.8%) cases of epithelial variant hepatoblastoma, 11 (11.8%) cases of mixed epithelial hepatoblastoma, and 41 (44.1%) cases of mixed epithelial and mesenchymal hepatoblastoma; 17 cases were not sub-classified. Seven (7.5%) cases had positive surgical margins, 69 (74.2%) had negative surgical margins, and 17 (18.3%) had unspecified surgical margin status. Twelve (12.9%) patients had microvascular involvement, 43 (46.2%) had no microvascular involvement, and 38 (40.9%) cases had unspecified microvascular status. Thirty-one patients underwent lymph node dissection, none of whom had positive lymph node involvement. Among the 9 patients with lung metastasis, one underwent metastasectomy.
Sixty-three (67.7%) patients received cisplatin-based postoperative chemotherapy, with a median of 6 (range, 1–12) cycles. Twenty-seven (29.0%) patients received no postoperative chemotherapy. During a median follow-up duration of 30.5 (range, 0.7–105.1) months, 84 (90.3%) cases survived without relapse, 9 (9.7%) experienced disease recurrence, and 4 (5.4%) died. For the 9 patients with lung metastasis, 5 of them survived with metastasis cleared, 1 died, and 3 were lost to follow-up.
Subgroup analysis of managements
In this study, the differences in management between patients without metastasis and patients with metastasis (1 of them had portal vein thrombosis at the same time) [cycle of neoadjuvant chemotherapy: 1(0-6) vs 2(0-8), p=0.060; cycle of preoperative TACE: 0(0-5) vs 1(0-7), p=0.589; cycle of postoperative chemotherapy: 6(0-12) vs 6(2-10), p=0.817], and patients with negative surgical margin and positive surgical margins [cycle of neoadjuvant chemotherapy: 1(0-8) vs 1(0-3), p=0.482; cycle of preoperative TACE: 1(0-5) vs 2(0-7), p=0.081; cycle of postoperative chemotherapy: 6(0-12) vs 7(2-12), p=0.946] were not statistically significant.
Failure among patients with tumour recurrence
Among the 9 patients with tumour recurrence, the median time from diagnosis to recurrence was 8.5 (range, 0.7-22.4) months, and the median time from surgery to recurrence was 3.6 (range, 0.5-22.0) months. Among the 4 patients who died as a result of tumour recurrence, the median time from diagnosis to death was 11.3 (range, 3.6–21.4) months. Their treatment and outcome information are summarised in Table 3. Five patients underwent wedge resection, and 1 underwent left hepatectomy associated with a positive surgical margin.
The 2-year event-free survival (EFS) and overall survival (OS) rates were 89.4±3.4%, and 95.2±2.4% (Figs. 1A and 2A), respectively. The 2-year EFS and OS rates were significantly better among patients without metastasis (no metastasis vs metastasis: EFS, 93.5±3.7% vs 46.7±19.0%, p=0.002, OS, 97.6±2.4% vs 61.0±18.1%, p=0.005) (Figs. 1C and 2C). The 2-year EFS rates were significantly better among patients without microvascular involvement (No vs Involvement: EFS, 95.3±3.3% vs 67.3±16.0%, p=0.022), while the 2-year OS rates were similar (OS, 97.7±2.3% vs 90.0±9.5%, p=0.313). The differences of the 2-year EFS and OS rates of patients with PRETEXT stage IV hepatoblastoma (Ⅱ vs Ⅲ vs Ⅳ: EFS, 84.0±6.7% vs 95.7±4.3% vs 66.7±27.2%, p=0.225. OS, 90.1±5.5% vs 95.5±4.4% vs 100.0%, p=0.547), positive surgical margins (negative vs positive: EFS, 92.0±3.5% vs 64.3±21.0%, p=0.100. OS, 95.0±2.8% vs 83.3±15.2%, p=0.369) were not statistically significant. The 2-year EFS and OS rates were also similar among patients treated with different preoperative strategies (Chemotherapy only vs TACE only vs Both: EFS, 94.7±5.1% vs 91.7±5.6% vs 85.6±6.7%, p=0.542. OS, 94.1±5.7% vs 95.7±4.3% vs 96.7±3.3% p=0.845) (Figs. 1D and 2D).