Tandem High-dose Chemotherapy without Craniospinal Irradiation in Treatment of Non-metastatic Malignant Brain Tumors in Very Young Children

J Korean Med Sci. 2020 Dec 14;35(48):e405. doi: 10.3346/jkms.2020.35.e405.


Background: Infants and very young children with malignant brain tumors have a poorer survival and a higher risk for neurologic deficits. The present study evaluated the feasibility and effectiveness of multimodal treatment including tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) in minimizing use of radiotherapy (RT) in very young children with non-metastatic malignant brain tumors.

Methods: Twenty consecutive patients younger than 3 years were enrolled between 2004 and 2017. Tandem HDCT/auto-SCT was performed after six cycles of induction chemotherapy. Local RT was administered only to patients with post-operative gross residual tumor at older than 3 years. Since September 2015, early post-operative local RT for patients with atypical teratoid/rhabdoid tumor or primitive neuroectodermal tumor was administered.

Results: All 20 enrolled patients underwent the first HDCT/auto-SCT, and 18 proceeded to the second. Two patients died from toxicity during the second HDCT/auto-SCT, and four patients experienced relapse/progression (one localized and three metastatic), three of whom remained alive after salvage treatment including RT. A total of 17 patients remained alive at a median 7.8 (range, 2.5-5.7) years from diagnosis. Nine survivors received no RT, six survivors received local RT alone, and two survivors who experienced metastatic relapse after tandem HDCT/auto-SCT received both local and craniospinal RT. The 5-year overall, event-free, and craniospinal RT-free survival rates were 85.0% ± 8.0%, 70.0% ± 10.2%, and 75.0% ± 9.7%, respectively. Neuroendocrine and neurocognitive functions evaluated 5 years after tandem HDCT/auto-SCT were acceptable.

Conclusion: Our results suggest that non-metastatic malignant brain tumors in very young children could be treated with multimodal therapy including tandem HDCT/auto-SCT while minimizing RT, particularly craniospinal RT.

Keywords: Brain Tumor; Children; High-dose Chemotherapy; Radiation Therapy.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Brain Neoplasms / radiotherapy
  • Carboplatin / administration & dosage
  • Child, Preschool
  • Craniospinal Irradiation
  • Etoposide / administration & dosage
  • Female
  • Hearing Loss / etiology
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Humans
  • Induction Chemotherapy
  • Infant
  • Male
  • Neoplasm Recurrence, Local
  • Progression-Free Survival
  • Risk Factors
  • Salvage Therapy
  • Survival Rate
  • Thiotepa / administration & dosage
  • Transplantation, Autologous / adverse effects


  • Etoposide
  • Thiotepa
  • Carboplatin