Multi-institution prospective trial of reduced-dose craniospinal irradiation (23.4 Gy) followed by conformal posterior fossa (36 Gy) and primary site irradiation (55.8 Gy) and dose-intensive chemotherapy for average-risk medulloblastoma.
OBJECTIVE
Limiting the neurocognitive sequelae of radiotherapy (RT) has been an objective in the treatment of medulloblastoma. Conformal RT to less than the entire posterior fossa (PF) after craniospinal irradiation might reduce neurocognitive sequelae and requires evaluation.


METHODS
Between October 1996 and August 2003, 86 patients, 3-21 years of age, with newly diagnosed, average-risk medulloblastoma were treated in a prospective, institutional review board-approved, multi-institution trial of risk-adapted RT and dose-intensive chemotherapy. RT began within 28 days of definitive surgery and consisted of craniospinal irradiation (23.4 Gy), conformal PF RT (36.0 Gy), and primary site RT (55.8 Gy). The planning target volume for the primary site included the postoperative tumor bed surrounded by an anatomically confined margin of 2 cm that was then expanded with a geometric margin of 0.3-0.5 cm. Chemotherapy was initiated 6 weeks after RT and included four cycles of high-dose cyclophosphamide, cisplatin, and vincristine.


RESULTS
At a median follow-up of 61.2 months (range, 5.2-115.0 months), the estimated 5-year event-free survival and cumulative incidence of PF failure rate was 83.0% +/- 5.3% and 4.9% +/- 2.4% (+/- standard error), respectively. The targeting guidelines used in this study resulted in a mean reduction of 13% in the volume of the PF receiving doses >55 Gy compared with conventionally planned RT. The reductions in the dose to the temporal lobes, cochleae, and hypothalamus were statistically significant.


CONCLUSIONS
This prospective trial has demonstrated that irradiation of less than the entire PF after 23.4 Gy craniospinal irradiation for average-risk medulloblastoma results in disease control comparable to that after treatment of the entire PF.
Merchant
Thomas E
TE
Department of Radiological Sciences, Division of Radiation Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. thomas.merchant@stjude.org
Kun
Larry E
LE
Krasin
Matthew J
MJ
Wallace
Dana
D
Chintagumpala
Murali M
MM
Woo
Shiao Y
SY
Ashley
David M
DM
Sexton
Maree
M
Kellie
Stewart J
SJ
Ahern
Verity
V
Gajjar
Amar
A
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002528:Cerebellar Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage; D003072:Cognition Disorders / Q000517:prevention & control; D003131:Combined Modality Therapy / Q000379:methods; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015192:Infratentorial Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D008297:Male; D008527:Medulloblastoma / Q000188:drug therapy / Q000532:radiotherapy*; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000379:methods; D047368:Tumor Burden; D014750:Vincristine / Q000008:administration & dosage
D014750:Vincristine; D003520:Cyclophosphamide; D002945:Cisplatin