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

Abstract

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, 2.5−15.7) 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.

Tandem High-Dose Chemotherapy Increases the Risk of Secondary Malignant Neoplasm in Pediatric Solid Tumors

“…Autologous hematopoietic cell transplantation and highdose chemotherapy (HDCT) are widely used to improve the survival rate of pediatric patients with high-risk or relapsed solid tumors [3][4][5]. In our institution, we implemented tandem HDCT to improve the treatment outcomes of patients with high-risk solid tumors [6][7][8][9] and minimize radiation exposure in patients with brain tumors [7,10], which has shown some success, especially in improving survival. However, because HDCT regimens for solid tumors usually include high-dose alkylating agents and, in some cases, total body irradiation (TBI), HDCT could be a risk factor for SMN development.…”