Low-stage medulloblastoma: Final analysis of trial comparing standard-dose with reduced-dose neuraxis irradiation

Patrick R.M. Thomas, Melvin Deutsch, James L. Kepner, James M. Boyett, Jeffrey Krischer, Patricia Aronin, Leland Albright, Jeffrey C. Allen, Roger J. Packer, Rita Linggood, Raymond Mulhern, James A. Stehbens, James Langston, Philip Stanley, Patricia Duffner, Lucy Rorke, Joel Cherlow, Henry S. Friedman, Jonathan L. Finlay, Teresa J. ViettiLarry E. Kun

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Abstract

Purpose: To evaluate prospectively the effects on survival, relapse-free survival, and patterns of relapse of reduced-dose (23.4 Gy in 13 fractions) compared with standard-dose (36 Gy in 20 fractions) neuraxis irradiation in patients 3 to 21 years of age with low-stage medulloblastoma, minimal postoperative residual disease, and no evidence of neuraxis disease. Patients and Methods: The Pediatric Oncology Group and Children's Cancer Group randomized 126 patients to the study. All patients received posterior fossa irradiation to a total dose of 54 Gy in addition to the neuraxis treatment. Patients were staged postoperatively with contrast-enhanced cranial computed to mography, myelography, and CSF cytology. Of the registered patients, 38 were ineligible. Results: The planned interim analysis that resulted in closure of the protocol showed that patients randomized to the reduced neuraxis treatment had increased frequency of relapse. In the final analysis, eligible patients receiving standard-dose neuroxis irradiation had 67% event-free survival (EFS) at 5 years (SE = 7.4%), whereas eligible patients receiving reduced-dose neuroxis irradiation had 52% event-free survival at 5 years (SE = 7.7%) (P = .080). At 8 years, the respective EFS proportions were also 67% (SE = 8.8%) and 52% (SE = 11%) (P = .141). These data confirm the original one-sided conclusions but suggest that differences are less marked with time. Conclusion: Reduced-dose neuroxis irradiation (23.4 Gy) is associated with increased risk of early relapse, early isolated neuraxis relapse, and lower 5-year EFS and overall survival than standard irradiation (36 Gy). The 5-year EFS for patients receiving standard-dose irradiation is suboptimal, and improved techniques and/or therapies are needed to improve ultimate outcome. Chemotherapy may contribute to this improvement. (C) 2000 by American Society of Clinical Oncology.

Original languageEnglish (US)
Pages (from-to)3004-3011
Number of pages8
JournalJournal of Clinical Oncology
Volume18
Issue number16
DOIs
StatePublished - Jan 1 2000

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Medulloblastoma
Disease-Free Survival
Recurrence
Survival
Myelography
Residual Neoplasm
Cell Biology
Therapeutics
Pediatrics
Drug Therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Thomas, P. R. M., Deutsch, M., Kepner, J. L., Boyett, J. M., Krischer, J., Aronin, P., ... Kun, L. E. (2000). Low-stage medulloblastoma: Final analysis of trial comparing standard-dose with reduced-dose neuraxis irradiation. Journal of Clinical Oncology, 18(16), 3004-3011. https://doi.org/10.1200/JCO.2000.18.16.3004

Low-stage medulloblastoma : Final analysis of trial comparing standard-dose with reduced-dose neuraxis irradiation. / Thomas, Patrick R.M.; Deutsch, Melvin; Kepner, James L.; Boyett, James M.; Krischer, Jeffrey; Aronin, Patricia; Albright, Leland; Allen, Jeffrey C.; Packer, Roger J.; Linggood, Rita; Mulhern, Raymond; Stehbens, James A.; Langston, James; Stanley, Philip; Duffner, Patricia; Rorke, Lucy; Cherlow, Joel; Friedman, Henry S.; Finlay, Jonathan L.; Vietti, Teresa J.; Kun, Larry E.

In: Journal of Clinical Oncology, Vol. 18, No. 16, 01.01.2000, p. 3004-3011.

Research output: Contribution to journalArticle

Thomas, PRM, Deutsch, M, Kepner, JL, Boyett, JM, Krischer, J, Aronin, P, Albright, L, Allen, JC, Packer, RJ, Linggood, R, Mulhern, R, Stehbens, JA, Langston, J, Stanley, P, Duffner, P, Rorke, L, Cherlow, J, Friedman, HS, Finlay, JL, Vietti, TJ & Kun, LE 2000, 'Low-stage medulloblastoma: Final analysis of trial comparing standard-dose with reduced-dose neuraxis irradiation', Journal of Clinical Oncology, vol. 18, no. 16, pp. 3004-3011. https://doi.org/10.1200/JCO.2000.18.16.3004
Thomas, Patrick R.M. ; Deutsch, Melvin ; Kepner, James L. ; Boyett, James M. ; Krischer, Jeffrey ; Aronin, Patricia ; Albright, Leland ; Allen, Jeffrey C. ; Packer, Roger J. ; Linggood, Rita ; Mulhern, Raymond ; Stehbens, James A. ; Langston, James ; Stanley, Philip ; Duffner, Patricia ; Rorke, Lucy ; Cherlow, Joel ; Friedman, Henry S. ; Finlay, Jonathan L. ; Vietti, Teresa J. ; Kun, Larry E. / Low-stage medulloblastoma : Final analysis of trial comparing standard-dose with reduced-dose neuraxis irradiation. In: Journal of Clinical Oncology. 2000 ; Vol. 18, No. 16. pp. 3004-3011.
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abstract = "Purpose: To evaluate prospectively the effects on survival, relapse-free survival, and patterns of relapse of reduced-dose (23.4 Gy in 13 fractions) compared with standard-dose (36 Gy in 20 fractions) neuraxis irradiation in patients 3 to 21 years of age with low-stage medulloblastoma, minimal postoperative residual disease, and no evidence of neuraxis disease. Patients and Methods: The Pediatric Oncology Group and Children's Cancer Group randomized 126 patients to the study. All patients received posterior fossa irradiation to a total dose of 54 Gy in addition to the neuraxis treatment. Patients were staged postoperatively with contrast-enhanced cranial computed to mography, myelography, and CSF cytology. Of the registered patients, 38 were ineligible. Results: The planned interim analysis that resulted in closure of the protocol showed that patients randomized to the reduced neuraxis treatment had increased frequency of relapse. In the final analysis, eligible patients receiving standard-dose neuroxis irradiation had 67{\%} event-free survival (EFS) at 5 years (SE = 7.4{\%}), whereas eligible patients receiving reduced-dose neuroxis irradiation had 52{\%} event-free survival at 5 years (SE = 7.7{\%}) (P = .080). At 8 years, the respective EFS proportions were also 67{\%} (SE = 8.8{\%}) and 52{\%} (SE = 11{\%}) (P = .141). These data confirm the original one-sided conclusions but suggest that differences are less marked with time. Conclusion: Reduced-dose neuroxis irradiation (23.4 Gy) is associated with increased risk of early relapse, early isolated neuraxis relapse, and lower 5-year EFS and overall survival than standard irradiation (36 Gy). The 5-year EFS for patients receiving standard-dose irradiation is suboptimal, and improved techniques and/or therapies are needed to improve ultimate outcome. Chemotherapy may contribute to this improvement. (C) 2000 by American Society of Clinical Oncology.",
author = "Thomas, {Patrick R.M.} and Melvin Deutsch and Kepner, {James L.} and Boyett, {James M.} and Jeffrey Krischer and Patricia Aronin and Leland Albright and Allen, {Jeffrey C.} and Packer, {Roger J.} and Rita Linggood and Raymond Mulhern and Stehbens, {James A.} and James Langston and Philip Stanley and Patricia Duffner and Lucy Rorke and Joel Cherlow and Friedman, {Henry S.} and Finlay, {Jonathan L.} and Vietti, {Teresa J.} and Kun, {Larry E.}",
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T1 - Low-stage medulloblastoma

T2 - Final analysis of trial comparing standard-dose with reduced-dose neuraxis irradiation

AU - Thomas, Patrick R.M.

AU - Deutsch, Melvin

AU - Kepner, James L.

AU - Boyett, James M.

AU - Krischer, Jeffrey

AU - Aronin, Patricia

AU - Albright, Leland

AU - Allen, Jeffrey C.

AU - Packer, Roger J.

AU - Linggood, Rita

AU - Mulhern, Raymond

AU - Stehbens, James A.

AU - Langston, James

AU - Stanley, Philip

AU - Duffner, Patricia

AU - Rorke, Lucy

AU - Cherlow, Joel

AU - Friedman, Henry S.

AU - Finlay, Jonathan L.

AU - Vietti, Teresa J.

AU - Kun, Larry E.

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N2 - Purpose: To evaluate prospectively the effects on survival, relapse-free survival, and patterns of relapse of reduced-dose (23.4 Gy in 13 fractions) compared with standard-dose (36 Gy in 20 fractions) neuraxis irradiation in patients 3 to 21 years of age with low-stage medulloblastoma, minimal postoperative residual disease, and no evidence of neuraxis disease. Patients and Methods: The Pediatric Oncology Group and Children's Cancer Group randomized 126 patients to the study. All patients received posterior fossa irradiation to a total dose of 54 Gy in addition to the neuraxis treatment. Patients were staged postoperatively with contrast-enhanced cranial computed to mography, myelography, and CSF cytology. Of the registered patients, 38 were ineligible. Results: The planned interim analysis that resulted in closure of the protocol showed that patients randomized to the reduced neuraxis treatment had increased frequency of relapse. In the final analysis, eligible patients receiving standard-dose neuroxis irradiation had 67% event-free survival (EFS) at 5 years (SE = 7.4%), whereas eligible patients receiving reduced-dose neuroxis irradiation had 52% event-free survival at 5 years (SE = 7.7%) (P = .080). At 8 years, the respective EFS proportions were also 67% (SE = 8.8%) and 52% (SE = 11%) (P = .141). These data confirm the original one-sided conclusions but suggest that differences are less marked with time. Conclusion: Reduced-dose neuroxis irradiation (23.4 Gy) is associated with increased risk of early relapse, early isolated neuraxis relapse, and lower 5-year EFS and overall survival than standard irradiation (36 Gy). The 5-year EFS for patients receiving standard-dose irradiation is suboptimal, and improved techniques and/or therapies are needed to improve ultimate outcome. Chemotherapy may contribute to this improvement. (C) 2000 by American Society of Clinical Oncology.

AB - Purpose: To evaluate prospectively the effects on survival, relapse-free survival, and patterns of relapse of reduced-dose (23.4 Gy in 13 fractions) compared with standard-dose (36 Gy in 20 fractions) neuraxis irradiation in patients 3 to 21 years of age with low-stage medulloblastoma, minimal postoperative residual disease, and no evidence of neuraxis disease. Patients and Methods: The Pediatric Oncology Group and Children's Cancer Group randomized 126 patients to the study. All patients received posterior fossa irradiation to a total dose of 54 Gy in addition to the neuraxis treatment. Patients were staged postoperatively with contrast-enhanced cranial computed to mography, myelography, and CSF cytology. Of the registered patients, 38 were ineligible. Results: The planned interim analysis that resulted in closure of the protocol showed that patients randomized to the reduced neuraxis treatment had increased frequency of relapse. In the final analysis, eligible patients receiving standard-dose neuroxis irradiation had 67% event-free survival (EFS) at 5 years (SE = 7.4%), whereas eligible patients receiving reduced-dose neuroxis irradiation had 52% event-free survival at 5 years (SE = 7.7%) (P = .080). At 8 years, the respective EFS proportions were also 67% (SE = 8.8%) and 52% (SE = 11%) (P = .141). These data confirm the original one-sided conclusions but suggest that differences are less marked with time. Conclusion: Reduced-dose neuroxis irradiation (23.4 Gy) is associated with increased risk of early relapse, early isolated neuraxis relapse, and lower 5-year EFS and overall survival than standard irradiation (36 Gy). The 5-year EFS for patients receiving standard-dose irradiation is suboptimal, and improved techniques and/or therapies are needed to improve ultimate outcome. Chemotherapy may contribute to this improvement. (C) 2000 by American Society of Clinical Oncology.

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