Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma.
OBJECTIVE
To determine the event-free survival (EFS) and overall survival of children with average-risk medulloblastoma and treated with reduced-dose craniospinal radiotherapy (CSRT) and one of two postradiotherapy chemotherapies.


METHODS
Four hundred twenty-one patients between 3 years and 21 years of age with nondisseminated medulloblastoma (MB) were prospectively randomly assigned to treatment with 23.4 Gy of CSRT, 55.8 Gy of posterior fossa RT, plus one of two adjuvant chemotherapy regimens: lomustine (CCNU), cisplatin, and vincristine; or cyclophosphamide, cisplatin, and vincristine. Results Forty-two of 421 patients enrolled were excluded from analysis. Sixty-six of the remaining 379 patients had incompletely assessable postoperative studies. Five-year EFS and survival for the cohort of 379 patients was 81% +/- 2.1% and 86% +/- 9%, respectively (median follow-up over 5 years). EFS was unaffected by sex, race, age, treatment regimen, brainstem involvement, or excessive anaplasia. EFS was detrimentally affected by neuroradiographic unassessability. Patients with areas of frank dissemination had a 5-year EFS of 36% +/- 15%. Sixty-seven percent of progressions had some component of dissemination. There were seven second malignancies. Infections occurred more frequently on the cyclophosphamide arm and electrolyte abnormalities were more common on the CCNU regimen.


CONCLUSIONS
This study discloses an encouraging EFS rate for children with nondisseminated MB treated with reduced-dose craniospinal radiation and chemotherapy. Additional, careful, step-wise reductions in CSRT in adequately staged patients may be possible.
Packer
Roger J
RJ
Division of Neurology, Children's National Medical Center, Washington, DC 20010, USA. rpacker@cnmc.org
Gajjar
Amar
A
Vezina
Gilbert
G
Rorke-Adams
Lucy
L
Burger
Peter C
PC
Robertson
Patricia L
PL
Bayer
Lisa
L
LaFond
Deborah
D
Donahue
Bernadine R
BR
Marymont
MaryAnne H
MH
Muraszko
Karin
K
Langston
James
J
Sposto
Richard
R
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002528:Cerebellar Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008130:Lomustine / Q000008:administration & dosage; D008297:Male; D008527:Medulloblastoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000175:diagnosis; D011379:Prognosis; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D012307:Risk Factors; D016019:Survival Analysis; D014750:Vincristine / Q000008:administration & dosage
D014750:Vincristine; D008130:Lomustine; D003520:Cyclophosphamide; D002945:Cisplatin