Hyperfractionated accelerated radiotherapy in the Milan strategy for metastatic medulloblastoma.
OBJECTIVE
With a view to improving the prognosis for patients with metastatic medulloblastoma, we tested the efficacy and toxicity of a hyperfractionated accelerated radiotherapy (HART) regimen delivered after intensive sequential chemotherapy.


METHODS
Between 1998 and 2007, 33 consecutive patients received postoperative methotrexate (8 g/m(2)), etoposide (2.4 g/m(2)), cyclophosphamide (4 g/m(2)), and carboplatin (0.8 g/m(2)) in a 2-month schedule, then HART with a maximal dose to the neuraxis of 39 Gy (1.3 Gy/fraction, 2 fractions/d) and a posterior fossa boost up to 60 Gy (1.5 Gy/fraction,2 fractions/d). Patients with persistent disseminated disease before HART were consolidated with two myeloablative courses and circulating progenitor cell rescue.


RESULTS
Patients were classified as having M1 (n = 9), M2 (n = 6), M3 (n = 17), and M4 (n = 1) disease. Seven patients younger than 10 years old who achieved complete response after chemotherapy received a lower dose to the neuraxis (31.2 Gy). Twenty-two of the 32 assessable patients responded to chemotherapy; disease was stable in five patients and progressed in five patients. One septic death occurred before radiotherapy. Eight patients experienced relapse after a median of 12 months. Fourteen of the 33 patients underwent consolidation therapy after HART. With a median 82-month survivor follow-up, the 5-year event-free, progression-free, and overall survival rates were 70%, 72%, and 73%, respectively. No severe clinical complications of HART have emerged so far.


CONCLUSIONS
HART after intensive postoperative chemotherapy, followed by myeloablative chemotherapy in selected cases, proved feasible in children with metastatic medulloblastoma. The results of our treatment compare favorably with other series treated using conventional therapies.
Gandola
Lorenza
L
Radiotherapy Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale Tumori, Milano, Italy.
Massimino
Maura
M
Cefalo
Graziella
G
Solero
Carlo
C
Spreafico
Filippo
F
Pecori
Emilia
E
Riva
Daria
D
Collini
Paola
P
Pignoli
Emanuele
E
Giangaspero
Felice
F
Luksch
Roberto
R
Berretta
Serena
S
Poggi
Geraldina
G
Biassoni
Veronica
V
Ferrari
Andrea
A
Pollo
Bianca
B
Favre
Claudio
C
Sardi
Iacopo
I
Terenziani
Monica
M
Fossati-Bellani
Franca
F
D000293:Adolescent; D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D016190:Carboplatin / Q000008:administration & dosage; D002528:Cerebellar Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D019583:Dose Fractionation, Radiation; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy*; D008727:Methotrexate / Q000008:administration & dosage; D009362:Neoplasm Metastasis; D011879:Radiotherapy Dosage; D015996:Survival Rate; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide; D003520:Cyclophosphamide; D016190:Carboplatin; D008727:Methotrexate