|
|
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
Dr, Prof
Amar Gajjar MD a*,
Murali Chintagumpala MD h,
David Ashley MBBS j,
Stewart Kellie MBBS i,
Prof Larry E Kun MD b,
Prof Thomas E Merchant DO b,
Shaio Woo MD h,
Greg Wheeler MBBS j,
Valerie Ahern MBBS i,
Matthew J Krasin MD b,
Maryam Fouladi MD a,
Alberto Broniscer MD a,
Prof Robert Krance MD h,
Gregory A Hale MD a,
Clinton F Stewart PharmD f,
Robert Dauser MD h,
Prof Robert A Sanford MD d,
Christine Fuller MD g,
Ching Lau MD h,
Prof James M Boyett PhD c,
Dana Wallace MS c
and Richard J Gilbertson
MD e
a.
Department
of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA.
b.
Department
of Radiological Sciences, St Jude Children's Research Hospital,
Memphis, TN, USA.
c.
Department
of Biostatistics, St Jude Children's Research Hospital, Memphis, TN,
USA.
d.
Department
of Neurosurgery, St Jude Children's Research Hospital, Memphis, TN,
USA.
e.
Department
of Developmental Neurobiology, St Jude Children's Research Hospital,
Memphis, TN, USA.
f.
Department
of Pharmaceutical Sciences, St Jude Children's Research Hospital,
Memphis, TN, USA.
g.
Department
of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA.
h.
Texas
Children's Hospital, Baylor College of Medicine, Houston, TX, USA.
i.
Children's
Hospital at Westmead, Sydney, NSW, Australia.
j.
Children's
Cancer Centre, Murdoch Children's Research Institute, Royal Children's
Hospital, Melbourne, VIC, Australia.
-- *Correspondence to: Dr Amar Gajjar, Division of Neuro-Oncology,
St Jude Children's Research Hospital, 332 North Lauderdale St,
Memphis, TN 38105, USA. Email: amar.gajjar@stjude.org.
|
|
|
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 (≤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.
Findings.
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.
Interpretation.
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.
|
