Postoperative Chemotherapy and Delayed Radiation in Children Less Than Three Years of Age with Malignant Brain Tumors

Patricia K. Duffner, Marc E. Horowitz, Jeffrey P. Krischer, Henry S. Friedman, Peter C. Burger, Michael E. Cohen, Robert A. Sanford, Raymond K. Mulhern, Hector E. James, Carolyn R. Freeman, F. Glen Seidel, Larry E. Kun

Research output: Contribution to journalArticle

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Abstract

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 under 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., The survival of infants and very young children with brain tumors is significantly worse than that of older children, both overall and for specific types of tumor1,2. These infants are also at risk for substantial treatment-related neurotoxicity, including mental retardation, growth failure, and leukoencephalopathy37. Poor outcome and late treatment effects have engendered a reluctance to treat young children with brain tumors, especially with radiation therapy. At the time the present study was designed, many parents chose to withhold treatment rather than face the possibility of long-term sequelae. In response to these problems, members of the Pediatric…

Original languageEnglish (US)
Pages (from-to)1725-1731
Number of pages7
JournalNew England Journal of Medicine
Volume328
Issue number24
DOIs
StatePublished - Jun 17 1993

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Brain Neoplasms
Radiation
Drug Therapy
Radiotherapy
Vincristine
Glioma
Cyclophosphamide
Disease-Free Survival
Survival Rate
Confidence Intervals
Pediatrics
Primitive Neuroectodermal Tumors
Ependymoma
Medulloblastoma
Etoposide
Therapeutics
Intellectual Disability
Cognition
Cisplatin
Brain Stem

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Duffner, P. K., Horowitz, M. E., Krischer, J. P., Friedman, H. S., Burger, P. C., Cohen, M. E., ... Kun, L. E. (1993). Postoperative Chemotherapy and Delayed Radiation in Children Less Than Three Years of Age with Malignant Brain Tumors. New England Journal of Medicine, 328(24), 1725-1731. https://doi.org/10.1056/NEJM199306173282401

Postoperative Chemotherapy and Delayed Radiation in Children Less Than Three Years of Age with Malignant Brain Tumors. / Duffner, Patricia K.; Horowitz, Marc E.; Krischer, Jeffrey P.; Friedman, Henry S.; Burger, Peter C.; Cohen, Michael E.; Sanford, Robert A.; Mulhern, Raymond K.; James, Hector E.; Freeman, Carolyn R.; Seidel, F. Glen; Kun, Larry E.

In: New England Journal of Medicine, Vol. 328, No. 24, 17.06.1993, p. 1725-1731.

Research output: Contribution to journalArticle

Duffner, PK, Horowitz, ME, Krischer, JP, Friedman, HS, Burger, PC, Cohen, ME, Sanford, RA, Mulhern, RK, James, HE, Freeman, CR, Seidel, FG & Kun, LE 1993, 'Postoperative Chemotherapy and Delayed Radiation in Children Less Than Three Years of Age with Malignant Brain Tumors', New England Journal of Medicine, vol. 328, no. 24, pp. 1725-1731. https://doi.org/10.1056/NEJM199306173282401
Duffner, Patricia K. ; Horowitz, Marc E. ; Krischer, Jeffrey P. ; Friedman, Henry S. ; Burger, Peter C. ; Cohen, Michael E. ; Sanford, Robert A. ; Mulhern, Raymond K. ; James, Hector E. ; Freeman, Carolyn R. ; Seidel, F. Glen ; Kun, Larry E. / Postoperative Chemotherapy and Delayed Radiation in Children Less Than Three Years of Age with Malignant Brain Tumors. In: New England Journal of Medicine. 1993 ; Vol. 328, No. 24. pp. 1725-1731.
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abstract = "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 under 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., The survival of infants and very young children with brain tumors is significantly worse than that of older children, both overall and for specific types of tumor1,2. These infants are also at risk for substantial treatment-related neurotoxicity, including mental retardation, growth failure, and leukoencephalopathy3–7. Poor outcome and late treatment effects have engendered a reluctance to treat young children with brain tumors, especially with radiation therapy. At the time the present study was designed, many parents chose to withhold treatment rather than face the possibility of long-term sequelae. In response to these problems, members of the Pediatric…",
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T1 - Postoperative Chemotherapy and Delayed Radiation in Children Less Than Three Years of Age with Malignant Brain Tumors

AU - Duffner, Patricia K.

AU - Horowitz, Marc E.

AU - Krischer, Jeffrey P.

AU - Friedman, Henry S.

AU - Burger, Peter C.

AU - Cohen, Michael E.

AU - Sanford, Robert A.

AU - Mulhern, Raymond K.

AU - James, Hector E.

AU - Freeman, Carolyn R.

AU - Seidel, F. Glen

AU - Kun, Larry E.

PY - 1993/6/17

Y1 - 1993/6/17

N2 - 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 under 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., The survival of infants and very young children with brain tumors is significantly worse than that of older children, both overall and for specific types of tumor1,2. These infants are also at risk for substantial treatment-related neurotoxicity, including mental retardation, growth failure, and leukoencephalopathy3–7. Poor outcome and late treatment effects have engendered a reluctance to treat young children with brain tumors, especially with radiation therapy. At the time the present study was designed, many parents chose to withhold treatment rather than face the possibility of long-term sequelae. In response to these problems, members of the Pediatric…

AB - 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 under 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., The survival of infants and very young children with brain tumors is significantly worse than that of older children, both overall and for specific types of tumor1,2. These infants are also at risk for substantial treatment-related neurotoxicity, including mental retardation, growth failure, and leukoencephalopathy3–7. Poor outcome and late treatment effects have engendered a reluctance to treat young children with brain tumors, especially with radiation therapy. At the time the present study was designed, many parents chose to withhold treatment rather than face the possibility of long-term sequelae. In response to these problems, members of the Pediatric…

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