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Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors.

Publication ,  Journal Article
Duffner, PK; Horowitz, ME; Krischer, JP; Friedman, HS; Burger, PC; Cohen, ME; Sanford, RA; Mulhern, RK; James, HE; Freeman, CR
Published in: N Engl J Med
June 17, 1993

BACKGROUND: Among patients with malignant brain tumors, infants and very young children have the worst prognosis and the most severe treatment-related neurotoxic effects. Therefore, in 1986, the Pediatric Oncology Group began a study in which postoperative chemotherapy was given in order to permit a delay in the delivery of radiation to the developing brain. METHODS: Children under 36 months of age with biopsy-proved malignant brain tumors were treated postoperatively with two 28-day cycles of cyclophosphamide plus vincristine, followed by one 28-day cycle of cisplatin plus etoposide. This sequence was repeated until the disease progressed or for two years in 132 children 24 months of age at diagnosis and for one year in 66 children 24 to 36 months of age at diagnosis. After this, the patients received radiation therapy. The response to the first two cycles of chemotherapy was measured in 102 patients with residual postoperative disease. RESULTS: The first two cycles of cyclophosphamide and vincristine produced complete or partial responses in 39 percent of the 102 patients who could be evaluated. The response rates were highest among patients with medulloblastomas, malignant gliomas, or ependymomas. Patients with brain-stem gliomas or embryonal tumors (primitive neuroectodermal tumors) had little or no response. The progression-free survival rate was 41 percent at one year for children who were 24 to 36 months old at diagnosis and 39 percent at two years for those under 24 months of age at diagnosis. Multivariate analysis identified embryonal tumors as a significant adverse prognostic feature (relative risk, 2.2; 95 percent confidence interval, 1.4 to 3.4) and complete resection as a favorable feature (relative risk, 0.33; 95 percent confidence interval, 0.20 to 0.54). Complete responses to chemotherapy were associated with a progression-free survival rate approaching that achieved with gross total resection. A comparison of cognitive evaluations obtained at base line and after one year of chemotherapy revealed no evidence of deterioration in cognitive function. CONCLUSIONS: Chemotherapy appears to be an effective primary postoperative treatment for many malignant brain tumors in young children. Disease control for one or two years in a large minority of patients permitted a delay in the delivery of radiation and, on the basis of preliminary results, a reduction in neurotoxicity. For patients who had undergone total surgical resection or who had a complete response to chemotherapy, the results are sufficiently encouraging to suggest that radiation therapy may not be needed in this subgroup of children after at least one year of chemotherapy.

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Published In

N Engl J Med

DOI

ISSN

0028-4793

Publication Date

June 17, 1993

Volume

328

Issue

24

Start / End Page

1725 / 1731

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Survival Rate
  • Prospective Studies
  • Postoperative Period
  • Neoplasms, Germ Cell and Embryonal
  • Medulloblastoma
  • Male
  • Humans
  • Glioma
  • General & Internal Medicine
 

Citation

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Duffner, P. K., Horowitz, M. E., Krischer, J. P., Friedman, H. S., Burger, P. C., Cohen, M. E., … Freeman, C. R. (1993). Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors. N Engl J Med, 328(24), 1725–1731. https://doi.org/10.1056/NEJM199306173282401
Duffner, P. K., M. E. Horowitz, J. P. Krischer, H. S. Friedman, P. C. Burger, M. E. Cohen, R. A. Sanford, R. K. Mulhern, H. E. James, and C. R. Freeman. “Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors.N Engl J Med 328, no. 24 (June 17, 1993): 1725–31. https://doi.org/10.1056/NEJM199306173282401.
Duffner PK, Horowitz ME, Krischer JP, Friedman HS, Burger PC, Cohen ME, et al. Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors. N Engl J Med. 1993 Jun 17;328(24):1725–31.
Duffner, P. K., et al. “Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors.N Engl J Med, vol. 328, no. 24, June 1993, pp. 1725–31. Pubmed, doi:10.1056/NEJM199306173282401.
Duffner PK, Horowitz ME, Krischer JP, Friedman HS, Burger PC, Cohen ME, Sanford RA, Mulhern RK, James HE, Freeman CR. Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors. N Engl J Med. 1993 Jun 17;328(24):1725–1731.
Journal cover image

Published In

N Engl J Med

DOI

ISSN

0028-4793

Publication Date

June 17, 1993

Volume

328

Issue

24

Start / End Page

1725 / 1731

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Survival Rate
  • Prospective Studies
  • Postoperative Period
  • Neoplasms, Germ Cell and Embryonal
  • Medulloblastoma
  • Male
  • Humans
  • Glioma
  • General & Internal Medicine