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Background: The JPLT3-S (Japanese Study Group for Pediatric Liver Tumors-3) study, conducted cisplatin (CDDP) monotherapy for young children (<3 years old) with standard-risk hepatoblastoma (HB) using a central review system in Japan. In the previous JPLT2 study, cases with resectable tumors without any annotation factors in the PRETEXT (PRETreatment EXTent of disease) classification (standard-risk HB) showed favorable outcomes with treatment consisting of CDDP and pirarubicin, but showed toxicities and late complications. In the JPLT3-S trial, a less intense regimen consisting of CDDP alone was evaluated., Methods: Patients who were less than 3 years of age and with PRETEXT I, II, or III HB without any annotation factors (e.g., E1, E1a, E2, E2a, H1, N1, P2, P2a, V3, and V3a) were eligible for inclusion in this study. In this trial, the central radiological and pathological features of all patients were reviewed. The primary outcome was the 3-year progression-free survival (PFS)., Results: A total of 38 patients (23 female) were included. The median patient age was 12 months (range: 2-34). Two patients discontinued treatment because of progressive disease, and five patients discontinued treatment for other reasons. The 3-year PFS rate was 93.9% (95% confidence interval [CI]: 86.4%-100%). All 38 patients survived (follow-up period 38-98 months), and the OS rate was 100% (CI: 100). Eighteen of the 38 patients (47.4%) experienced ototoxicity as a late complication., Conclusion: CDDP monotherapy regimen is feasible in young patients with localized HB, as classified by a central review., (© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Two percent of pediatric malignancies arise primarily in the liver; roughly 60% of these cancers are hepatoblastoma (HB). Despite the rarity of these cases, international collaborative efforts have led to the consistent histological classification and staging systems, which facilitate ongoing clinical trials. Other primary liver malignancies seen in children include hepatocellular carcinoma (HCC) with or without underlying liver disease, fibrolamellar carcinoma (FLC), undifferentiated embryonal sarcoma of the liver (UESL), and hepatocellular neoplasm not otherwise specified (HCN-NOS). This review describes principles of surgical management of malignant pediatric primary liver tumors, within the context of comprehensive multidisciplinary care., (© 2024 Wiley Periodicals LLC.)

Purpose: Survival rates of patients with high-risk neuroblastoma are unacceptable. A time-intensified treatment strategy with delayed local treatment to control systemic diseases has been developed in Japan. We conducted a nationwide, prospective, single-arm clinical trial with delayed local treatment. This study evaluated the safety and efficacy of delayed surgery to increase treatment intensity., Patients and Methods: Seventy-five patients with high-risk neuroblastoma were enrolled in this study between May 2011 and September 2015. Delayed local treatment consisted of five courses of induction chemotherapy (cisplatin, pirarubicin, vincristine, and cyclophosphamide) and myeloablative high-dose chemotherapy (melphalan, etoposide, and carboplatin), followed by local tumor extirpation with surgery and irradiation. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), response rate, adverse events, and surgical complications., Results: Seventy-five patients were enrolled, and 64 were evaluable (stage 3, n = 8; stage 4, n = 56). The estimated 3-year PFS and OS rates (95% confidence interval [CI]) were 44.4% [31.8%-56.3%] and 80.7% [68.5%-88.5%], resspectively. The response rate of INRC after completion of the treatment protocol was 66% (42/64; 95% CI: 53%-77%; 23 CR [complete response], 10 VGPR [very good partial response], and nine PR [partial response]). None of the patients died during the protocol treatment or within 30 days of completion. Grade 4 adverse effects, excluding hematological adverse effects, occurred in 48% of patients [31/64; 95% CI: 36%-61%]. Major Surgical complications were observed in 25% of patients [13/51; 95% CI: 14%-40%]., Conclusion: This study indicates that delayed local treatment is feasible and shows promising efficacy, suggesting that this treatment should be considered further in a comparative study of high-risk neuroblastoma., (© 2024 Wiley Periodicals LLC.)

Background: The SIOPEL-4 study has demonstrated that dose-dense cisplatin-based chemotherapy dramatically improves outcome in children with high-risk hepatoblastoma in western countries. However, the feasibility and safety of this regimen have not been clarified in Japanese patients., Methods: A pilot study, JPLT3-H, was designed to evaluate the safety profile of the SIOPEL-4 regimen in Japanese children with newly diagnosed hepatoblastoma with either metastatic disease or low alpha-fetoprotein., Results: A total of 15 patients (three female) were enrolled. Median age was 2 years (range, 0-14). Three patients were PRETEXT II (where PRETEXT is PRETreatment EXTent of disease), six PRETEXT III, and six PRETEXT IV. All patients had lung metastasis, none had low alpha-fetoprotein. Eight patients completed the prescribed treatment, and seven patients discontinued therapy prematurely, four due to progressive disease and three due to causes other than severe toxicity. Grade 4 neutropenia was documented in most patients in preoperative cycles A1-3 (11/15 in A1, 9/11 in A2, and 7/11 in A3) and in all considering all cycles. Grade 3-4 thrombocytopenia and grade 3 anemia were also frequently observed. Patients experienced several episodes of grade 3 febrile neutropenia, but none had grade 4 febrile neutropenia or severe infections. One patient had grade 3 heart failure only in the first cycle. Other grade 3 or 4 toxicities were hypomagnesemia, anorexia, nausea, mucositis, liver enzyme elevation, fever, infection, and fatigue. There were no unexpected severe toxicities., Conclusion: The toxicity profile of JPLT3-H was comparable to that of SIOPEL-4. Dose-dense cisplatin-based chemotherapy may be feasible among Japanese patients with high-risk hepatoblastoma., (© 2021 Wiley Periodicals LLC.)

Purpose: Treatment outcomes for hepatoblastoma have improved markedly in the contemporary treatment era, principally due to therapy intensification, with overall survival increasing from 35% in the 1970s to 90% at present. Unfortunately, these advancements are accompanied by an increased incidence of toxicities. A detailed analysis of age as a prognostic factor may support individualized risk-based therapy stratification., Methods: We evaluated 1605 patients with hepatoblastoma included in the CHIC database to assess the relationship between event-free survival (EFS) and age at diagnosis. Further analysis included the age distribution of additional risk factors and the interaction of age with other known prognostic factors., Results: Risk for an event increases progressively with increasing age at diagnosis. This pattern could not be attributed to the differential distribution of other known risk factors across age. Newborns and infants are not at increased risk of treatment failure. The interaction between age and other adverse risk factors demonstrates an attenuation of prognostic relevance with increasing age in the following categories: metastatic disease, AFP < 100 ng/mL, and tumor rupture., Conclusion: Risk for an event increased with advancing age at diagnosis. Increased age attenuates the prognostic influence of metastatic disease, low AFP, and tumor rupture. Age could be used to modify recommended chemotherapy intensity., (© 2020 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals, Inc.)

Background: Excellent outcomes of the extreme procedure of liver resection (LR) for advanced hepatoblastoma (HB) have been achieved in recent reports. However, liver transplantation (LT) remains the only surgical treatment for patients with unresectable HB. The aim of this study was to evaluate our retrospective data for cases of advanced HB necessitating surgical intervention and analyze the prognostic factors of recurrence by comparing patients with tumors resected by LR and LT., Patients and Methods: We retrospectively reviewed 24 children with PRETEXT II/III/IV tumors that required consideration for LT between August 2011 and September 2016., Result: The staging at the time of the diagnosis was PRETEXT II/III/IV in 1/13/10 patients, respectively, while the preoperative staging after neoadjuvant chemotherapy was POSTTEXT II/III/IV in 5/17/2 patients. Among those 24 patients, complete resection of the primary tumor was achieved with LT in 12 patients and LR in 12 patients. A high serum level of alpha-fetoprotein (AFP) at the time of surgery, no significant decrease in the rate of change of AFP, and low tumor shrinkage rate were related to the risk of tumor recurrence, and patients with tumors resected by LR with those risks had a higher recurrence rate than those without them. The overall survival was higher in patients with tumors resected by LT (100%) than in patients with tumors resected by LR., Conclusion: Patients with advanced HB with a poor response to chemotherapy should definitively be prioritized for primary LT, given the possibility of vascular invasion and microscopic residual tumor., (© 2018 Wiley Periodicals, Inc.)

Minimally invasive surgery has become widely recognized and is commonly used for the diagnosis and treatment of neuroblastoma. However, in post-chemotherapy status or during reoperations, it is occasionally difficult to precisely locate small neuroblastoma lesions, and this becomes prominent in endoscopic surgeries, in which tactile sense is essentially lost. Herein, we report our preliminary experience in two abdominal neuroblastoma cases undergoing laparoscopic tumor resection with aid of intraoperative (123)I- metaiodobenzylguanidine (MIBG) radioguidance using a specifically designed gamma-probe. The procedure enables easier localization of viable neuroblastoma tissue, provided that the tumor shows moderate to high MIBG uptake., (© 2015 Wiley Periodicals, Inc.)