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.

Methotrexate (MTX) has been shown to impair neurocognitive outcomes. Because the cumulative dose of MTX used in the standard treatment of osteosarcoma is higher compared to the treatment of other childhood cancers, we analyzed the neurocognitive performance among 12 survivors of childhood osteosarcoma exposed to high-dose MTX at our institution. Prospective longitudinal evaluations of neurocognitive functioning using the Japanese Wechsler Intelligence Scale for Children-4th Edition were performed. As a result, we observed age-appropriate development of neurocognitive performance among osteosarcoma survivors. In conclusion, cognitive development was not adversely affected in this cohort of childhood osteosarcoma survivors treated with HD-MTX.

Background: Treatment of intracranial germ cell tumors (GCTs) involves radiation therapy to the whole ventricle or the whole neuroaxis, but late sequelae are a concern. Therefore, an alternative modality is needed to reduce the overreliance on radiation therapy. Intrathecal methotrexate (IT-MTX) was examined as a partial alternative to radiotherapy. Procedure: Low-risk (LR) patients (germinoma) were treated with four cycles of cisplatin, etoposide, and IT-MTX, while intermediate-risk (IR) (human chorionic gonadotropin [HCG]-producing germinoma) and high-risk (HR) (non-germinomatous GCT) patients were treated with five cycles of cisplatin, etoposide, cyclophosphamide, and IT-MTX. Local irradiation of 24 Gy was performed for the LR and IR patients, while irradiation with 51.2 Gy was performed for the HR cases. For patients with multifocal diseases and/or tumors extending to the 3rd ventricle, whole ventricle irradiation was performed. Results: A total of 57 patients were enrolled, of which three withdrew consent. Thus, 54 patients were included in the outcome analysis. The 5-year progression-free survival and overall survival were 92.0% (standard error 4.4%) and 100%, respectively, for 28 LR and 10 IR patients (median follow-up: 63 months), and 86.7% (8.8%) and 93.3% (6.4%) (median follow-up: 67 months), respectively, for 16 HR patients. The major toxicity was hematological, and most patients experienced grade 4. Conclusion: The toxicity of chemotherapy containing IT-MTX was limited, and the results suggested that this regimen could reduce the need for radiotherapy.