Metastasis stage, adjuvant treatment, and residual tumor are prognostic factors for medulloblastoma in children: Conclusions from the Children's Cancer Group 921 randomized phase III study

Paul M. Zeltzer, James M. Boyett, Jonathan L. Finlay, A. Leland Albright, Lucy B. Rorke, Jerrold M. Milstein, Jeffrey C. Allen, Kenneth Stevens, Philip Stanley, Hao Li, Jeffrey H. Wisoff, J. Russell Geyer, Patsy McGuire-Cullen, James A. Stehbens, Susan B. Shurin, Roger J. Packer

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Abstract

Purpose: From 1986 to 1992, 'eight-drugs-in-one-day' (8-in-1) chemotherapy both before and after radiation therapy (XRT) (54 Gy tumor/36 Gy neuraxis) was compared with vincristine, lomustine (CCNU), and prednisone (VCP) after XRT in children with untreated, high-stage medulloblastoma (MB). Patients and Methods: Two hundred three eligible patients with an institutional diagnosis of MB were stratified by local invasion and metastatic stage (Chang T/M) and randomized to therapy. Median time at risk from study entry was 7.0 years. Results: Survival and progression-free survival (PFS) ± SE at 7 years were 55% ± 5% and 54% ± 5%, respectively. VCP was superior to 8-in-1 chemotherapy, with 5-year PFS rates of 63% ± 5% versus 45% ± 5%, respectively (P = .006). Upon central neuropathology review, 188 patients were confirmed as having MB and were the subjects for analyses of prognostic factors. Children aged 1.5 to younger than 3 years had inferior 5-year estimates of PFS, compared with children 3 years old or older (P = .0014; 32% ± 10% v 58% ± 4%, respectively). For MB patients 3 years of age or older, the prognostic effect of tumor spread (M0 v M1 v M2+) on PFS was powerful (P = .0006); 5-year PFS rates were 70% ± 5%, 57% ± 10%, and 40% ± 8%, respectively. PFS distributions at 5 years for patients with M0 tumors with less than 1.5 cm2 of residual tumor, versus ≥ 1.5 cm2 of residual tumor by scan, were significantly different (P = .023; 78% ± 6% v 54% ± 11%, respectively). Conclusion: VCP plus XRT is a superior adjuvant combination compared with 8-in-1 chemotherapy plus XRT. For patients with M0 tumors, residual tumor bulk (not extent of resection) is a predictor for PFS. Patients with M0 tumors, ≥ 3 years with ≤ 1.5 cm2 residual tumor, had a 78% ± 6% 5-year PFS rate. Children younger than 3 years old who received a reduced XRT dosage had the lowest survival rate.

Original languageEnglish (US)
Pages (from-to)832-845
Number of pages14
JournalJournal of Clinical Oncology
Volume17
Issue number3
StatePublished - Mar 1999
Externally publishedYes

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Medulloblastoma
Residual Neoplasm
Disease-Free Survival
Neoplasm Metastasis
Neoplasms
Survival Rate
Lomustine
Therapeutics
Drug Therapy
Vincristine
Prednisone
Radiotherapy
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Metastasis stage, adjuvant treatment, and residual tumor are prognostic factors for medulloblastoma in children : Conclusions from the Children's Cancer Group 921 randomized phase III study. / Zeltzer, Paul M.; Boyett, James M.; Finlay, Jonathan L.; Albright, A. Leland; Rorke, Lucy B.; Milstein, Jerrold M.; Allen, Jeffrey C.; Stevens, Kenneth; Stanley, Philip; Li, Hao; Wisoff, Jeffrey H.; Geyer, J. Russell; McGuire-Cullen, Patsy; Stehbens, James A.; Shurin, Susan B.; Packer, Roger J.

In: Journal of Clinical Oncology, Vol. 17, No. 3, 03.1999, p. 832-845.

Research output: Contribution to journalArticle

Zeltzer, PM, Boyett, JM, Finlay, JL, Albright, AL, Rorke, LB, Milstein, JM, Allen, JC, Stevens, K, Stanley, P, Li, H, Wisoff, JH, Geyer, JR, McGuire-Cullen, P, Stehbens, JA, Shurin, SB & Packer, RJ 1999, 'Metastasis stage, adjuvant treatment, and residual tumor are prognostic factors for medulloblastoma in children: Conclusions from the Children's Cancer Group 921 randomized phase III study', Journal of Clinical Oncology, vol. 17, no. 3, pp. 832-845.
Zeltzer, Paul M. ; Boyett, James M. ; Finlay, Jonathan L. ; Albright, A. Leland ; Rorke, Lucy B. ; Milstein, Jerrold M. ; Allen, Jeffrey C. ; Stevens, Kenneth ; Stanley, Philip ; Li, Hao ; Wisoff, Jeffrey H. ; Geyer, J. Russell ; McGuire-Cullen, Patsy ; Stehbens, James A. ; Shurin, Susan B. ; Packer, Roger J. / Metastasis stage, adjuvant treatment, and residual tumor are prognostic factors for medulloblastoma in children : Conclusions from the Children's Cancer Group 921 randomized phase III study. In: Journal of Clinical Oncology. 1999 ; Vol. 17, No. 3. pp. 832-845.
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title = "Metastasis stage, adjuvant treatment, and residual tumor are prognostic factors for medulloblastoma in children: Conclusions from the Children's Cancer Group 921 randomized phase III study",
abstract = "Purpose: From 1986 to 1992, 'eight-drugs-in-one-day' (8-in-1) chemotherapy both before and after radiation therapy (XRT) (54 Gy tumor/36 Gy neuraxis) was compared with vincristine, lomustine (CCNU), and prednisone (VCP) after XRT in children with untreated, high-stage medulloblastoma (MB). Patients and Methods: Two hundred three eligible patients with an institutional diagnosis of MB were stratified by local invasion and metastatic stage (Chang T/M) and randomized to therapy. Median time at risk from study entry was 7.0 years. Results: Survival and progression-free survival (PFS) ± SE at 7 years were 55{\%} ± 5{\%} and 54{\%} ± 5{\%}, respectively. VCP was superior to 8-in-1 chemotherapy, with 5-year PFS rates of 63{\%} ± 5{\%} versus 45{\%} ± 5{\%}, respectively (P = .006). Upon central neuropathology review, 188 patients were confirmed as having MB and were the subjects for analyses of prognostic factors. Children aged 1.5 to younger than 3 years had inferior 5-year estimates of PFS, compared with children 3 years old or older (P = .0014; 32{\%} ± 10{\%} v 58{\%} ± 4{\%}, respectively). For MB patients 3 years of age or older, the prognostic effect of tumor spread (M0 v M1 v M2+) on PFS was powerful (P = .0006); 5-year PFS rates were 70{\%} ± 5{\%}, 57{\%} ± 10{\%}, and 40{\%} ± 8{\%}, respectively. PFS distributions at 5 years for patients with M0 tumors with less than 1.5 cm2 of residual tumor, versus ≥ 1.5 cm2 of residual tumor by scan, were significantly different (P = .023; 78{\%} ± 6{\%} v 54{\%} ± 11{\%}, respectively). Conclusion: VCP plus XRT is a superior adjuvant combination compared with 8-in-1 chemotherapy plus XRT. For patients with M0 tumors, residual tumor bulk (not extent of resection) is a predictor for PFS. Patients with M0 tumors, ≥ 3 years with ≤ 1.5 cm2 residual tumor, had a 78{\%} ± 6{\%} 5-year PFS rate. Children younger than 3 years old who received a reduced XRT dosage had the lowest survival rate.",
author = "Zeltzer, {Paul M.} and Boyett, {James M.} and Finlay, {Jonathan L.} and Albright, {A. Leland} and Rorke, {Lucy B.} and Milstein, {Jerrold M.} and Allen, {Jeffrey C.} and Kenneth Stevens and Philip Stanley and Hao Li and Wisoff, {Jeffrey H.} and Geyer, {J. Russell} and Patsy McGuire-Cullen and Stehbens, {James A.} and Shurin, {Susan B.} and Packer, {Roger J.}",
year = "1999",
month = "3",
language = "English (US)",
volume = "17",
pages = "832--845",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
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}

TY - JOUR

T1 - Metastasis stage, adjuvant treatment, and residual tumor are prognostic factors for medulloblastoma in children

T2 - Conclusions from the Children's Cancer Group 921 randomized phase III study

AU - Zeltzer, Paul M.

AU - Boyett, James M.

AU - Finlay, Jonathan L.

AU - Albright, A. Leland

AU - Rorke, Lucy B.

AU - Milstein, Jerrold M.

AU - Allen, Jeffrey C.

AU - Stevens, Kenneth

AU - Stanley, Philip

AU - Li, Hao

AU - Wisoff, Jeffrey H.

AU - Geyer, J. Russell

AU - McGuire-Cullen, Patsy

AU - Stehbens, James A.

AU - Shurin, Susan B.

AU - Packer, Roger J.

PY - 1999/3

Y1 - 1999/3

N2 - Purpose: From 1986 to 1992, 'eight-drugs-in-one-day' (8-in-1) chemotherapy both before and after radiation therapy (XRT) (54 Gy tumor/36 Gy neuraxis) was compared with vincristine, lomustine (CCNU), and prednisone (VCP) after XRT in children with untreated, high-stage medulloblastoma (MB). Patients and Methods: Two hundred three eligible patients with an institutional diagnosis of MB were stratified by local invasion and metastatic stage (Chang T/M) and randomized to therapy. Median time at risk from study entry was 7.0 years. Results: Survival and progression-free survival (PFS) ± SE at 7 years were 55% ± 5% and 54% ± 5%, respectively. VCP was superior to 8-in-1 chemotherapy, with 5-year PFS rates of 63% ± 5% versus 45% ± 5%, respectively (P = .006). Upon central neuropathology review, 188 patients were confirmed as having MB and were the subjects for analyses of prognostic factors. Children aged 1.5 to younger than 3 years had inferior 5-year estimates of PFS, compared with children 3 years old or older (P = .0014; 32% ± 10% v 58% ± 4%, respectively). For MB patients 3 years of age or older, the prognostic effect of tumor spread (M0 v M1 v M2+) on PFS was powerful (P = .0006); 5-year PFS rates were 70% ± 5%, 57% ± 10%, and 40% ± 8%, respectively. PFS distributions at 5 years for patients with M0 tumors with less than 1.5 cm2 of residual tumor, versus ≥ 1.5 cm2 of residual tumor by scan, were significantly different (P = .023; 78% ± 6% v 54% ± 11%, respectively). Conclusion: VCP plus XRT is a superior adjuvant combination compared with 8-in-1 chemotherapy plus XRT. For patients with M0 tumors, residual tumor bulk (not extent of resection) is a predictor for PFS. Patients with M0 tumors, ≥ 3 years with ≤ 1.5 cm2 residual tumor, had a 78% ± 6% 5-year PFS rate. Children younger than 3 years old who received a reduced XRT dosage had the lowest survival rate.

AB - Purpose: From 1986 to 1992, 'eight-drugs-in-one-day' (8-in-1) chemotherapy both before and after radiation therapy (XRT) (54 Gy tumor/36 Gy neuraxis) was compared with vincristine, lomustine (CCNU), and prednisone (VCP) after XRT in children with untreated, high-stage medulloblastoma (MB). Patients and Methods: Two hundred three eligible patients with an institutional diagnosis of MB were stratified by local invasion and metastatic stage (Chang T/M) and randomized to therapy. Median time at risk from study entry was 7.0 years. Results: Survival and progression-free survival (PFS) ± SE at 7 years were 55% ± 5% and 54% ± 5%, respectively. VCP was superior to 8-in-1 chemotherapy, with 5-year PFS rates of 63% ± 5% versus 45% ± 5%, respectively (P = .006). Upon central neuropathology review, 188 patients were confirmed as having MB and were the subjects for analyses of prognostic factors. Children aged 1.5 to younger than 3 years had inferior 5-year estimates of PFS, compared with children 3 years old or older (P = .0014; 32% ± 10% v 58% ± 4%, respectively). For MB patients 3 years of age or older, the prognostic effect of tumor spread (M0 v M1 v M2+) on PFS was powerful (P = .0006); 5-year PFS rates were 70% ± 5%, 57% ± 10%, and 40% ± 8%, respectively. PFS distributions at 5 years for patients with M0 tumors with less than 1.5 cm2 of residual tumor, versus ≥ 1.5 cm2 of residual tumor by scan, were significantly different (P = .023; 78% ± 6% v 54% ± 11%, respectively). Conclusion: VCP plus XRT is a superior adjuvant combination compared with 8-in-1 chemotherapy plus XRT. For patients with M0 tumors, residual tumor bulk (not extent of resection) is a predictor for PFS. Patients with M0 tumors, ≥ 3 years with ≤ 1.5 cm2 residual tumor, had a 78% ± 6% 5-year PFS rate. Children younger than 3 years old who received a reduced XRT dosage had the lowest survival rate.

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