Survival and prognostic factors following radiation therapy and chemotherapy for ependymomas in children: A report of the children's cancer group

Patricia L. Robertson, Paul M. Zeltzer, James M. Boyett, Lucy B. Rorke, Jeffrey C. Allen, J. Russell Geyer, Philip Stanley, Hao Li, A. Leland Albright, Patricia Mcguire-Cullen, Jonathan L. Finlay, Kenneth Stevens, Jerrold M. Milstein, Roger J. Packer, Jeffrey Wisoff

Research output: Contribution to journalArticle

273 Citations (Scopus)

Abstract

Object. Ependymomas in children continue to generate controversy regarding their histological diagnosis and grading, optimal management, and possible prognostic factors. To increase our knowledge of these tumors the authors addressed these issues in a cohort of children with prospectively staged ependymomas treated with radiotherapy and chemotherapy. Methods. Children between the ages of 2 and 17.3 years harboring an intracranial ependymoma confirmed by a central review of the tumor's pathological characteristics were treated according to Children's Cancer Group Protocol 921 from 1986 to 1992. Treatment following surgery and postoperative tumor staging (including brain computerized tomography or magnetic resonance [MR] imaging, spinal MR imaging or myelography, and cerebrospinal fluid cytological investigation) included craniospinal irradiation with a local boost to the primary tumor and patient randomization to receive adjuvant chemotherapy with either 1) CCNU, vincristine, and prednisone, or 2) the eight-drugs-in-1-day regimen. Centralized review of the tumor pathological characteristics revealed 20 ependymomas and 12 anaplastic ependymomas in the 32 children included in the study. Diagnoses made at the individual institutions included anaplastic (malignant) ependymoma (15 patients), ependymoma (four patients), ependymoblastoma (nine patients), ependymoastrocytoma (one patient), and primitive neuroectodermal tumor (three patients), which were discordant with the centralized review diagnosis in 22 of 32 cases. Only three of the 32 patients had metastatic disease (two with M1 and one with M3 stages). At surgery, 47% of tumors were estimated to be totally resected. Among the 14 of 17 patients who suffered a relapse and were evaluated for site of relapse, 10 (71%) had an isolated local relapse, three (21%) had concurrent local and metastatic relapse, and only one (7%) had an isolated metastatic relapse. Kaplan-Meier estimates of 5-year progression- free survival (PFS) and overall survival rates were 50 ± 10% and 64 ± 9%, respectively. Conclusions. Predictors of PFS duration included an estimate of the extent of resection made at surgery (total compared with less than total, p = 0.0001) and the amount of residual tumor on postoperative imaging as verified by centralized radiological review (≤ 1.5 cm2 compared with > 1.5 cm2, p <0.0001). No other factors, including centrally reviewed tumor histopathological type, location, metastasis and tumor (M and T) stages, patient age, race, gender, or chemotherapy treatment regimen significantly correlated with PFS duration. The pattern of predominantly local relapse and the important influence of residual tumor or the extent of resection on PFS duration confirms a prevailing impression that local disease control is the major factor in the prediction of outcome of ependymoma. Survival rates were comparable with those reported by other investigators who have treated patients with similar doses of radiation and no chemotherapy.

Original languageEnglish (US)
Pages (from-to)695-703
Number of pages9
JournalJournal of Neurosurgery
Volume88
Issue number4
StatePublished - Apr 1998
Externally publishedYes

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Ependymoma
Radiotherapy
Drug Therapy
Survival
Recurrence
Neoplasms
Disease-Free Survival
Primitive Neuroectodermal Tumors
Residual Neoplasm
Survival Rate
Craniospinal Irradiation
Magnetic Resonance Imaging
Neuroepithelial Neoplasms
Lomustine
Myelography
Neoplasm Staging
Kaplan-Meier Estimate
Vincristine
Adjuvant Chemotherapy
Random Allocation

Keywords

  • Anaplastic ependymoma
  • Brain tumor
  • Children
  • Ependymoma
  • Prognosis

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Robertson, P. L., Zeltzer, P. M., Boyett, J. M., Rorke, L. B., Allen, J. C., Geyer, J. R., ... Wisoff, J. (1998). Survival and prognostic factors following radiation therapy and chemotherapy for ependymomas in children: A report of the children's cancer group. Journal of Neurosurgery, 88(4), 695-703.

Survival and prognostic factors following radiation therapy and chemotherapy for ependymomas in children : A report of the children's cancer group. / Robertson, Patricia L.; Zeltzer, Paul M.; Boyett, James M.; Rorke, Lucy B.; Allen, Jeffrey C.; Geyer, J. Russell; Stanley, Philip; Li, Hao; Albright, A. Leland; Mcguire-Cullen, Patricia; Finlay, Jonathan L.; Stevens, Kenneth; Milstein, Jerrold M.; Packer, Roger J.; Wisoff, Jeffrey.

In: Journal of Neurosurgery, Vol. 88, No. 4, 04.1998, p. 695-703.

Research output: Contribution to journalArticle

Robertson, PL, Zeltzer, PM, Boyett, JM, Rorke, LB, Allen, JC, Geyer, JR, Stanley, P, Li, H, Albright, AL, Mcguire-Cullen, P, Finlay, JL, Stevens, K, Milstein, JM, Packer, RJ & Wisoff, J 1998, 'Survival and prognostic factors following radiation therapy and chemotherapy for ependymomas in children: A report of the children's cancer group', Journal of Neurosurgery, vol. 88, no. 4, pp. 695-703.
Robertson, Patricia L. ; Zeltzer, Paul M. ; Boyett, James M. ; Rorke, Lucy B. ; Allen, Jeffrey C. ; Geyer, J. Russell ; Stanley, Philip ; Li, Hao ; Albright, A. Leland ; Mcguire-Cullen, Patricia ; Finlay, Jonathan L. ; Stevens, Kenneth ; Milstein, Jerrold M. ; Packer, Roger J. ; Wisoff, Jeffrey. / Survival and prognostic factors following radiation therapy and chemotherapy for ependymomas in children : A report of the children's cancer group. In: Journal of Neurosurgery. 1998 ; Vol. 88, No. 4. pp. 695-703.
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abstract = "Object. Ependymomas in children continue to generate controversy regarding their histological diagnosis and grading, optimal management, and possible prognostic factors. To increase our knowledge of these tumors the authors addressed these issues in a cohort of children with prospectively staged ependymomas treated with radiotherapy and chemotherapy. Methods. Children between the ages of 2 and 17.3 years harboring an intracranial ependymoma confirmed by a central review of the tumor's pathological characteristics were treated according to Children's Cancer Group Protocol 921 from 1986 to 1992. Treatment following surgery and postoperative tumor staging (including brain computerized tomography or magnetic resonance [MR] imaging, spinal MR imaging or myelography, and cerebrospinal fluid cytological investigation) included craniospinal irradiation with a local boost to the primary tumor and patient randomization to receive adjuvant chemotherapy with either 1) CCNU, vincristine, and prednisone, or 2) the eight-drugs-in-1-day regimen. Centralized review of the tumor pathological characteristics revealed 20 ependymomas and 12 anaplastic ependymomas in the 32 children included in the study. Diagnoses made at the individual institutions included anaplastic (malignant) ependymoma (15 patients), ependymoma (four patients), ependymoblastoma (nine patients), ependymoastrocytoma (one patient), and primitive neuroectodermal tumor (three patients), which were discordant with the centralized review diagnosis in 22 of 32 cases. Only three of the 32 patients had metastatic disease (two with M1 and one with M3 stages). At surgery, 47{\%} of tumors were estimated to be totally resected. Among the 14 of 17 patients who suffered a relapse and were evaluated for site of relapse, 10 (71{\%}) had an isolated local relapse, three (21{\%}) had concurrent local and metastatic relapse, and only one (7{\%}) had an isolated metastatic relapse. Kaplan-Meier estimates of 5-year progression- free survival (PFS) and overall survival rates were 50 ± 10{\%} and 64 ± 9{\%}, respectively. Conclusions. Predictors of PFS duration included an estimate of the extent of resection made at surgery (total compared with less than total, p = 0.0001) and the amount of residual tumor on postoperative imaging as verified by centralized radiological review (≤ 1.5 cm2 compared with > 1.5 cm2, p <0.0001). No other factors, including centrally reviewed tumor histopathological type, location, metastasis and tumor (M and T) stages, patient age, race, gender, or chemotherapy treatment regimen significantly correlated with PFS duration. The pattern of predominantly local relapse and the important influence of residual tumor or the extent of resection on PFS duration confirms a prevailing impression that local disease control is the major factor in the prediction of outcome of ependymoma. Survival rates were comparable with those reported by other investigators who have treated patients with similar doses of radiation and no chemotherapy.",
keywords = "Anaplastic ependymoma, Brain tumor, Children, Ependymoma, Prognosis",
author = "Robertson, {Patricia L.} and Zeltzer, {Paul M.} and Boyett, {James M.} and Rorke, {Lucy B.} and Allen, {Jeffrey C.} and Geyer, {J. Russell} and Philip Stanley and Hao Li and Albright, {A. Leland} and Patricia Mcguire-Cullen and Finlay, {Jonathan L.} and Kenneth Stevens and Milstein, {Jerrold M.} and Packer, {Roger J.} and Jeffrey Wisoff",
year = "1998",
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language = "English (US)",
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TY - JOUR

T1 - Survival and prognostic factors following radiation therapy and chemotherapy for ependymomas in children

T2 - A report of the children's cancer group

AU - Robertson, Patricia L.

AU - Zeltzer, Paul M.

AU - Boyett, James M.

AU - Rorke, Lucy B.

AU - Allen, Jeffrey C.

AU - Geyer, J. Russell

AU - Stanley, Philip

AU - Li, Hao

AU - Albright, A. Leland

AU - Mcguire-Cullen, Patricia

AU - Finlay, Jonathan L.

AU - Stevens, Kenneth

AU - Milstein, Jerrold M.

AU - Packer, Roger J.

AU - Wisoff, Jeffrey

PY - 1998/4

Y1 - 1998/4

N2 - Object. Ependymomas in children continue to generate controversy regarding their histological diagnosis and grading, optimal management, and possible prognostic factors. To increase our knowledge of these tumors the authors addressed these issues in a cohort of children with prospectively staged ependymomas treated with radiotherapy and chemotherapy. Methods. Children between the ages of 2 and 17.3 years harboring an intracranial ependymoma confirmed by a central review of the tumor's pathological characteristics were treated according to Children's Cancer Group Protocol 921 from 1986 to 1992. Treatment following surgery and postoperative tumor staging (including brain computerized tomography or magnetic resonance [MR] imaging, spinal MR imaging or myelography, and cerebrospinal fluid cytological investigation) included craniospinal irradiation with a local boost to the primary tumor and patient randomization to receive adjuvant chemotherapy with either 1) CCNU, vincristine, and prednisone, or 2) the eight-drugs-in-1-day regimen. Centralized review of the tumor pathological characteristics revealed 20 ependymomas and 12 anaplastic ependymomas in the 32 children included in the study. Diagnoses made at the individual institutions included anaplastic (malignant) ependymoma (15 patients), ependymoma (four patients), ependymoblastoma (nine patients), ependymoastrocytoma (one patient), and primitive neuroectodermal tumor (three patients), which were discordant with the centralized review diagnosis in 22 of 32 cases. Only three of the 32 patients had metastatic disease (two with M1 and one with M3 stages). At surgery, 47% of tumors were estimated to be totally resected. Among the 14 of 17 patients who suffered a relapse and were evaluated for site of relapse, 10 (71%) had an isolated local relapse, three (21%) had concurrent local and metastatic relapse, and only one (7%) had an isolated metastatic relapse. Kaplan-Meier estimates of 5-year progression- free survival (PFS) and overall survival rates were 50 ± 10% and 64 ± 9%, respectively. Conclusions. Predictors of PFS duration included an estimate of the extent of resection made at surgery (total compared with less than total, p = 0.0001) and the amount of residual tumor on postoperative imaging as verified by centralized radiological review (≤ 1.5 cm2 compared with > 1.5 cm2, p <0.0001). No other factors, including centrally reviewed tumor histopathological type, location, metastasis and tumor (M and T) stages, patient age, race, gender, or chemotherapy treatment regimen significantly correlated with PFS duration. The pattern of predominantly local relapse and the important influence of residual tumor or the extent of resection on PFS duration confirms a prevailing impression that local disease control is the major factor in the prediction of outcome of ependymoma. Survival rates were comparable with those reported by other investigators who have treated patients with similar doses of radiation and no chemotherapy.

AB - Object. Ependymomas in children continue to generate controversy regarding their histological diagnosis and grading, optimal management, and possible prognostic factors. To increase our knowledge of these tumors the authors addressed these issues in a cohort of children with prospectively staged ependymomas treated with radiotherapy and chemotherapy. Methods. Children between the ages of 2 and 17.3 years harboring an intracranial ependymoma confirmed by a central review of the tumor's pathological characteristics were treated according to Children's Cancer Group Protocol 921 from 1986 to 1992. Treatment following surgery and postoperative tumor staging (including brain computerized tomography or magnetic resonance [MR] imaging, spinal MR imaging or myelography, and cerebrospinal fluid cytological investigation) included craniospinal irradiation with a local boost to the primary tumor and patient randomization to receive adjuvant chemotherapy with either 1) CCNU, vincristine, and prednisone, or 2) the eight-drugs-in-1-day regimen. Centralized review of the tumor pathological characteristics revealed 20 ependymomas and 12 anaplastic ependymomas in the 32 children included in the study. Diagnoses made at the individual institutions included anaplastic (malignant) ependymoma (15 patients), ependymoma (four patients), ependymoblastoma (nine patients), ependymoastrocytoma (one patient), and primitive neuroectodermal tumor (three patients), which were discordant with the centralized review diagnosis in 22 of 32 cases. Only three of the 32 patients had metastatic disease (two with M1 and one with M3 stages). At surgery, 47% of tumors were estimated to be totally resected. Among the 14 of 17 patients who suffered a relapse and were evaluated for site of relapse, 10 (71%) had an isolated local relapse, three (21%) had concurrent local and metastatic relapse, and only one (7%) had an isolated metastatic relapse. Kaplan-Meier estimates of 5-year progression- free survival (PFS) and overall survival rates were 50 ± 10% and 64 ± 9%, respectively. Conclusions. Predictors of PFS duration included an estimate of the extent of resection made at surgery (total compared with less than total, p = 0.0001) and the amount of residual tumor on postoperative imaging as verified by centralized radiological review (≤ 1.5 cm2 compared with > 1.5 cm2, p <0.0001). No other factors, including centrally reviewed tumor histopathological type, location, metastasis and tumor (M and T) stages, patient age, race, gender, or chemotherapy treatment regimen significantly correlated with PFS duration. The pattern of predominantly local relapse and the important influence of residual tumor or the extent of resection on PFS duration confirms a prevailing impression that local disease control is the major factor in the prediction of outcome of ependymoma. Survival rates were comparable with those reported by other investigators who have treated patients with similar doses of radiation and no chemotherapy.

KW - Anaplastic ependymoma

KW - Brain tumor

KW - Children

KW - Ependymoma

KW - Prognosis

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