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) evaluated central review system in Japan. In the previous JPLT2 study, cases with resectable tumors without any annotation factors in the PRETEXT classification (standard risk HB) showed favorable outcomes by the therapies consisted of CDDP and pirarubicin, but showed toxicities and late complications. In this JPLT3-S trial, less intensity regimen consisted of CDDP alone were evaluated in the young children (< 3 years old) with standard risk HB. Methods: Patients who were less than three years of age, who had 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, we introduced central radiological and pathological reviews of all patients. The primary outcome was 3-year progression-free survival (PFS). Results: A total of 38 patients (23 female) were included. The median patient age was 12 (range, 2-34) months. 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 to 100). All 38 patients survived (follow-up period 38-98 months), and the OS rate was 100% (confidence interval, 100). There were no cases with late complication without ototoxicity. Conclusion: CDDP monotherapy regimen is feasible in young patients with localized HB classified by central review.

Background: Metronomic chemotherapy (MC) is based on chronic administration of chemotherapeutic agents at minimally toxic doses without prolonged drug-free breaks. MC has a multitargeted action of tumor angiogenesis inhibition and anticancer immune response stimulation and may also directly affect tumor cells to induce tumor dormancy. At our institute, MC has been introduced to treat patients with refractory/relapsed pediatric tumors. Methods: We retrospectively analyzed the data of pediatric patients with relapsed/refractory solid tumors who received treatment, including low-dose continuous administration of anti-cancer drugs. Results: Of the 18 patients, the disease statuses at the initiation of MC were complete remission ( n = 2), partial remission/stable disease ( n = 5), and progressive disease ( n = 11). The overall survival rate was 61% at 12 months and 34% at 24 months, and the progression-free survival rate was 21% at 12 and 24 months. Eleven of 18 patients, with tumor stabilization or maintained remission/stable disease, showed certain advantages in terms of overall survival rate. Even if limited to progressive disease, the survival time of responders was prolonged compared to non-responders (median 19.4 months vs. 4.7 months, P = 0.012). Conclusion: Approximately half of the patients demonstrated temporal tumor stabilization and improved survival time, although most patients had progressive disease, and MC was administered as palliative therapy. Large-scale studies on pediatric MC are rare; however, previous reports and the present study support the conclusion that MC has the potential to play an important role in pediatric cancer treatment during the advanced stage, both in terms of prolonging life and maintaining quality of life.

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is caused by heterozygous germline mutations in the fumarate hydratase (FH) gene and is associated with increased susceptibility to cutaneous leiomyomas, uterine leiomyomas, and renal cell carcinoma (RCC). This report describes a seven-year-old male who developed a large right kidney tumor with multiple cystic lesions that contained enhanced solid components. Whole-exome sequencing identified his germline mutation in the FH gene and its loss of heterozygosity in the tumor. This was the youngest-onset case of HLRCC-associated RCC to date. This report may affect the starting age for future RCC-surveillance programs for patients with HLRCC.

Background: The prognosis of metastatic hepatoblastoma remains poor; to improve it, pulmonary metastasis must be controlled. Indocyanine green (ICG) fluorescent imaging has been used recently for lung metastasectomy. The objective of our study was to clarify the usefulness of ICG imaging for lung metastasectomy of hepatoblastoma using detailed clinicopathological analysis. Procedure: Patients with hepatoblastoma who underwent resection of pulmonary metastases with ICG fluorescent imaging were studied using retrospective analysis of clinical information, a review of their surgical records, and a histological analysis of their metastatic nodules. Results: Sixteen patients were enrolled. In total, 61 ICG-imaging-guided pulmonary metastasectomies were performed, and 350 ICG-positive and 23 ICG-negative specimens were identified. Tumors were confirmed in 250 of the ICG-positive specimens, including eight nonpalpable nodules, on microscopic examination. One hundred ICG-positive specimens and histologically tumor-negative specimens showed histological changes suggesting the regression of a tumor or bloodstream disturbance. The palpable ICG-negative tumors showed more-severe atypia than the ICG-positive tumors. Conclusions: This study demonstrates the high sensitivity of ICG imaging in detecting metastatic lesions of hepatoblastoma. Histological examinations suggested that ICG imaging detects not only tumor cells, but also nontumorous pulmonary tissues affected by bloodstream disturbance. Because a number of false-positive specimens were detected, further optimization of the dose of ICG and the timing of its administration may be required for thorough metastasectomy. Several false-negative specimens were also detected, suggesting the presence of ICG-negative metastatic tumors. Palpation during operation and imaging studies remain essential for detecting metastatic lesions, even in the era of ICG imaging.