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.

Appropriate high-dose chemotherapy (HDC) for high-risk neuroblastoma has not yet been established. In Japan, a unique HDC regimen (called double-conditioning regimen) comprising two cycles of total 800 mg/m2 of thiotepa and total 280 mg/m2 of melphalan is widely used. To re-evaluate the safety and the efficacy of this regimen for high-risk neuroblastoma, the medical records of 41 patients with high-risk neuroblastoma who underwent the double-conditioning regimen followed by autologous peripheral blood stem cell rescue between 2002 and 2012 were reviewed. MYCN-amplified high-risk neuroblastomas were observed in 23 patients. All patients underwent intensive multidrug induction chemotherapy, but none underwent anti-GD2 antibody immunotherapy. The primary tumor was resected at the adequate time point. The median follow-up duration for living patients was 9.2 years (range = 5.5–14.0 years). The 5-year event-free survival (EFS) and overall survival (OS) rates from treatment initiation were 41.5% ± 7.7% and 56.1% ± 7.8%, respectively. The 5-year EFS of MYCN-amplified high-risk neuroblastoma patients was 60.9% ± 10.2%, which was significantly superior compared to MYCN-non-amplified high-risk neuroblastoma patients (16.7% ± 8.8%; P < 0.001). MYCN amplification was the most favorable prognostic factor for EFS (hazard ratio = 0.29; 95% confidence interval = 0.12–0.66). Of the 41 patients, 3 died because of regimen-related toxicity (infection, n = 2; microangiopathy, n = 1). The double-conditioning regimen with thiotepa and melphalan is effective for high-risk neuroblastoma, especially in patients with MYCN amplification. However, the double-conditioning regimen is toxic and warrants special attention in clinical practice.