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

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

• Ma Y
• Lim DH
• Cho H
• Lee JW
• Sung KW
• Yoo KH
• Koo HH
• Shin HJ
• Suh YL

• KMID: 2509526
• DOI: http://doi.org/10.3346/jkms.2020.35.e405

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, eventfree, 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.

Keyword

Brain Tumor; High-dose Chemotherapy; Radiation Therapy; Children

Figure

• 

  Fig. 1 Treatment scheme.CT = chemotherapy, HDCT = high-dose chemotherapy, L-RT = local radiotherapy, CSRT = craniospinal radiotherapy, ATRT = atypical teratoid/rhabdoid tumor, PNET = primitive neuroectodermal tumor, R = post-operative gross residual tumor, M = metastases.

• 

  Fig. 2 Flow of patients.HDCT1= first high-dose chemotherapy, HDCT2 = second HDCT, CR = complete response, CCR = continuous CR, PR = partial response, PD = progressive disease, REL = relapse, TRM = treatment-related mortality, off-Tx = off treatment, RT = radiotherapy, MB = medulloblastoma, AE = anaplastic ependymoma, CPC = Choroid plexus carcinoma, ATRT = atypical teratoid/rhabdoid tumor, ETMR = embryonal tumor with multilayered rosette, C19MC-altered, GM = glioblastoma multiforme, IMT = immature teratoma, MFH = malignant fibrous histiocytoma, ET = embryonal tumor, NOS.

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  Fig. 3 Survival rates. (A) The 5-year OS and EFS rates were 85.0% ± 8.0% and 70.0% ± 10.2%, respectively. (B) The 5-year CSRT-free survival was 75.0% ± 9.7%. (C) The EFS was lower in patients with gross residual tumor than in those without (37.5% ± 17.1% versus 91.7% ± 8.0%, P = 0.012). (D) There was no difference in EFS between embryonal and non-embryonal tumors.OS = overall survival, EFS = event-free survival, CSRT = craniospinal radiotherapy, GTR = gross total resection.

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  Fig. 4 Vertical growth during follow-up.Dx = diagnosis, Off-Tx = off treatment, GH = growth hormone.

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