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Hiyama et al. Hepatoma Res 2021;7:44 https://dx.doi.org/10.20517/2394-5079.2021.21 Page 9 of 12

Figure 3. Resection rates of primary tumors in the JPLT-1 and JPLT-2 trials. The resection rate of primary tumors was 86.4% in JPLT-2
vs. 71.6% in JPLT-1 (chi-square = 13.743, P = 0.0002). The resection rate was significantly higher in JPLT-2 than JPLT-1. The resection
rate of the patients without distant metastasis was 90.7% in JPLT-2, which was a significant improvement compared with the rate in
JPLT-1 (81.4%). In particular, the resectability of non-metastatic PRETEXT IV tumors was significantly improved in JPLT-2 compared
with JPLT-1 (73.2% vs. 40.0%). JPLT: Japanese study group for Pediatric Liver Tumors.

Figure 4. Event-free survival (EFS) rates of the cases with microscopically positive or negative (complete resection) margins: (A)
among all resected cases; and (B) among non-metastatic cases that underwent primary tumor resection. Five-year EFS rates are shown
in this figure. The cases with microscopically positive margins showed poorer outcomes compared to those with negative margins.
MicroMPR: Microscopically marginal positive resection.

In a previous analysis of the same cohort , resectability was evaluated by imaging, and the patients were
[3]
classified according to tumor response as responders (complete or partial response) or non-responders
(stable disease or progressive disease) according to the RECIST criteria. Chemo-responders and tumor
resectability after neoadjuvant CTx were correlated with favorable outcomes. In that analysis, the resectable
cases included the microMPR cases. The tumor response was significantly correlated with resectability.
Indeed, among the patients without metastasis, EFS was significantly longer in the chemo-responders, but
OS showed no significant difference. This result might suggest that poor chemosensitivity is also correlated
with residual tumor cells at the surgical margin.

We also compared the resection rate in our study with that in the previous JPLT-1 trial . The resection rate
[29]
was significantly higher in JPLT-2, especially in the non-metastatic or PRETEXT IV cases. The resection