Reduced radiotherapy by combining chemotherapy with intrathecal
administration of methotrexate for pediatric patients with intracranial
germ cell tumor
Abstract
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.