Hiyama Eiso, Hishiki Tomoro, Yoshimura Kenichi, Krailo Mark, Maibach Rudolf, Haeberle Beate, Rangaswami Arun, Lopez-Terrada Dolores, Malogolowkin Marcio H, Ansari Marc, Alaggio Rita, O'Neill Allison F, Trobaugh-Lotrario Angela D, Watanabe Kenichiro, Schmid Irene, Ranganathan Sarangarajan, Tanaka Yukichi, Inoue Takeshi, Piao Jin, Lin Jason, Czauderna Piotr, Meyers Rebecka L, Aronson Daniel C
Natural Science for Basic Research and Development, Department of Pediatric Surgery, Hiroshima University Hospital, Hiroshima University, Hiroshima, Japan.
Department of Pediatric Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
EClinicalMedicine. 2024 Sep 9;76:102811. doi: 10.1016/j.eclinm.2024.102811. eCollection 2024 Oct.
In the treatment of resectable hepatoblastoma (HB), it has not been established whether upfront surgery (UF) at diagnosis or neoadjuvant chemotherapy and delayed surgery (DL) is preferred. We compared patients with localized HB who underwent either UF, or DL after neoadjuvant chemotherapy in the Children's Hepatic tumors International Collaboration (CHIC) database of 1605 cases enrolled in eight multicenter hepatoblastoma trials between 1988 and 2010.
Among the 512 resectable HB patients who had PRETEXT (PRETreament EXTent of disease) I or II unruptured tumors at diagnosis without extrahepatic invasion, distant metastases, or massive vascular invasion, 172 underwent UF and 340 underwent DL. The primary outcomes were event-free and overall survivals after start of treatment in these two groups. Survival analysis was performed using the Kaplan-Maier analysis with long-rank tests and multivariable Cox regression models.
Complete resection rates were comparable (93.6% in UF and 89.7% in DL). The total cycles of chemotherapy of DL (median:6) were significantly more than those of UF (median:4) ( < 0.01). The 5-year event-free survival (EFS) was 90.6% and 86.6% ( = 0.89) in the UF and DL cohorts, respectively. The surgical complications, recurrence rates, and late complications were not significantly different between the cohorts but the EFS rates of DL patients with a low alpha-fetoprotein (AFP) level (100-999 ng/mL) or older age at diagnosis (≥3 years old) were significantly worse than others.
The outcomes, surgical resectability, and complications were not significantly different between the UF and DL groups. Eligible patients with a low AFP level (<1000 ng/mL) or older age (≥3 years old) showed better outcomes in the UF group and might be considered for initial resection.
European Network for Cancer Research in Children and Adolescents, funded through the Framework Program 7 of the European Commission; Children's Oncology Group Cure Search grant contributed by the Hepatoblastoma Foundation; Practical Research for Innovative Cancer Control and Project Promoting Clinical Trials for Development of New Drugs and Medical Devices, Japan Agency for Medical Research and Development; Japan Society for the Promotion of Science; and Swiss Cancer Research grant.
在可切除性肝母细胞瘤（HB）的治疗中，究竟是诊断时直接手术（UF）还是新辅助化疗后延迟手术（DL）更为可取，目前尚无定论。我们在儿童肝肿瘤国际协作组（CHIC）数据库中，比较了接受UF或新辅助化疗后DL的局限性HB患者，该数据库纳入了1988年至2010年间八项多中心肝母细胞瘤试验的1605例病例。
在512例诊断时具有PRETEXT（疾病预处理范围）I或II期未破裂肿瘤、无肝外侵犯、远处转移或大量血管侵犯的可切除性HB患者中，172例行UF，340例行DL。主要结局是这两组开始治疗后的无事件生存率和总生存率。采用Kaplan-Meier分析、长秩检验和多变量Cox回归模型进行生存分析。
完全切除率相当（UF组为93.6%，DL组为89.7%）。DL组的化疗总周期数（中位数：6）显著多于UF组（中位数：4）（<0.01）。UF组和DL组的5年无事件生存率（EFS）分别为90.6%和86.6%（=0.89）。两组的手术并发症、复发率和晚期并发症无显著差异，但甲胎蛋白（AFP）水平低（100 - 999 ng/mL）或诊断时年龄较大（≥3岁）的DL患者的EFS率明显低于其他患者。
UF组和DL组的结局、手术可切除性和并发症无显著差异。AFP水平低（<1000 ng/mL）或年龄较大（≥3岁）的符合条件患者在UF组中结局较好，可考虑初始切除。
欧洲儿童和青少年癌症研究网络，由欧盟框架计划7资助；儿童肿瘤组治愈搜索基金，由肝母细胞瘤基金会提供；日本医疗研究与开发机构的创新癌症控制实际研究和促进新药及医疗器械开发临床试验项目；日本科学促进会；以及瑞士癌症研究基金。
