Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial.
BACKGROUND
Current treatment for medulloblastoma, which includes postoperative radiotherapy and 1 year of chemotherapy, does not cure many children with high-risk disease. We aimed to investigate the effectiveness of risk-adapted radiotherapy followed by a shortened period of dose-intense chemotherapy in children with medulloblastoma.


METHODS
After resection, patients were classified as having average-risk medulloblastoma (< or = 1.5 cm2 residual tumour and no metastatic disease) or high-risk medulloblastoma (> 1.5 cm2 residual disease or metastatic disease localised to neuraxis) medulloblastoma. All patients received risk-adapted craniospinal radiotherapy (23.4 Gy for average-risk disease and 36.0-39.6 Gy for high-risk disease) followed by four cycles of cyclophosphamide-based, dose-intensive chemotherapy. Patients were assessed regularly for disease status and treatment side-effects. The primary endpoint was 5-year event-free survival; we also measured overall survival. This study is registered with ClinicalTrials.gov, number NCT00003211.


RESULTS
Of 134 children with medulloblastoma who underwent treatment (86 average-risk, 48 high-risk), 119 (89%) completed the planned protocol. No treatment-related deaths occurred. 5-year overall survival was 85% (95% CI 75-94) in patients in the average-risk group and 70% (54-84) in those in the high-risk group (p=0.04); 5-year event-free survival was 83% (73-93) and 70% (55-85), respectively (p=0.046). For the 116 patients whose histology was reviewed centrally, histological subtype correlated with 5-year event-free survival (p=0.04): 84% (74-95) for classic histology, 77% (49-100) for desmoplastic tumours, and 57% (33-80) for large-cell anaplastic tumours.


CONCLUSIONS
Risk-adapted radiotherapy followed by a shortened schedule of dose-intensive chemotherapy can be used to improve the outcome of patients with high-risk medulloblastoma.
Gajjar
Amar
A
Department of Oncology, St Jude Children's Research Hospital, Memphis, TN 38105, USA. amar.gajjar@stjude.org
Chintagumpala
Murali
M
Ashley
David
D
Kellie
Stewart
S
Kun
Larry E
LE
Merchant
Thomas E
TE
Woo
Shaio
S
Wheeler
Greg
G
Ahern
Valerie
V
Krasin
Matthew J
MJ
Fouladi
Maryam
M
Broniscer
Alberto
A
Krance
Robert
R
Hale
Gregory A
GA
Stewart
Clinton F
CF
Dauser
Robert
R
Sanford
Robert A
RA
Fuller
Christine
C
Lau
Ching
C
Boyett
James M
JM
Wallace
Dana
D
Gilbertson
Richard J
RJ
D000293:Adolescent; D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D002528:Cerebellar Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D016371:Cranial Irradiation / Q000379:methods*; D003520:Cyclophosphamide / Q000627:therapeutic use*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D011446:Prospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D015996:Survival Rate; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide