Outcome of children with centrally reviewed low-grade gliomas treated with chemotherapy with or without radiotherapy on Children's Cancer Group high-grade glioma study CCG-945.
BACKGROUND
The objectives of the current study were to determine the outcome of children who were treated with chemotherapy and radiotherapy on the Children's Cancer Group (CCG) high-grade glioma protocol (CCG-945) who were diagnosed with low-grade gliomas on post hoc central pathologic review and to identify clinical and biologic features associated with prognosis.


METHODS
Between 1985 and 1991, 250 children with institutionally classified high-grade gliomas were enrolled on CCG-945. Patients older than 24 months with intracranial lesions were assigned randomly to receive either lomustine, vincristine, and prednisone (control regimen) or the 8-drugs-in-1-day regimen (experimental regimen); younger patients and those with primary spinal cord tumors were assigned nonrandomly to the experimental regimen. Central independent review by 5 neuropathologists led to a reclassification of low-grade glioma in 70 patients, who were the focus of the current study.


RESULTS
The study involved 42 males and 28 females (median age, 7.7 years) with a median follow-up of 10.4 years. At 5 years, the progression-free survival (PFS) rate was 63% +/- 6%, and the overall survival (OS) rate was 79% +/- 5%, compared with a PFS rate of 19% +/- 3% (P < 0.0001) and an OS rate of 22% +/- 3% (P < 0.0001) in the remainder of the cohort. Significantly poorer 5-year PFS was seen in children younger than 24 months, those with fibrillary astrocytoma, and those with posterior fossa tumors. Patients demonstrated a modest improvement in PFS but no improvement in OS compared with children with low-grade gliomas who were treated with contemporary chemotherapy-alone approaches.


CONCLUSIONS
The current report calls attention to the importance of central pathologic review in large multiinstitutional trials of children with gliomas and suggests that aggressive front-line combined chemoradiotherapy does not confer a survival advantage in this highly selected population of patients.
Fouladi
Maryam
M
Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. maryam.fouladi@stjude.org
Hunt
Daniel L
DL
Pollack
Ian F
IF
Dueckers
Gregor
G
Burger
Peter C
PC
Becker
Laurence E
LE
Yates
Allen J
AJ
Gilles
Floyd H
FH
Davis
Richard L
RL
Boyett
James M
JM
Finlay
Jonathan L
JL
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001932:Brain Neoplasms / Q000532:radiotherapy / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008130:Lomustine / Q000008:administration & dosage; D008297:Male; D011239:Prednisolone / Q000008:administration & dosage; D011379:Prognosis; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
D014750:Vincristine; D008130:Lomustine; D011239:Prednisolone