Supratentorial primitive neuroectodermal tumors (S-PNET) in children: A prospective experience with adjuvant intensive chemotherapy and hyperfractionated accelerated radiotherapy.
OBJECTIVE
Supratentorial primitive neuroectodermal tumors (S-PNET) are rare and have a grim prognosis, frequently taking an aggressive course with local relapse and metastatic spread. We report the results of a mono-institutional therapeutic trial.


METHODS
We enrolled 15 consecutive patients to preradiation chemotherapy (CT) consisting of high-dose methotrexate, high-dose etoposide, high-dose cyclophosphamide, and high-dose carboplatin, craniospinal irradiation (CSI) with hyperfractionated accelerated radiotherapy (HART) plus focal boost, maintenance with vincristine/lomustine or consolidation with high-dose thiotepa followed by autologous stem-cell rescue.


RESULTS
Median age was 9 years; 7 were male, 8 female. Site of disease was pineal in 3, elsewhere in 12. Six patients were had no evidence of disease after surgery (NED). Of those with evidence of disease after surgery (ED), 2 had central nervous system spread. Of the 9 ED patients, 2 had complete response (CR) and 2 partial response (PR) after CT, 4 stable disease, and 1 progressive disease. Of the 7 ED patients before radiotherapy, 1 had CR, 4 PR, and 2 minor response, thus obtaining a 44% CR + PR after CT and 71% after HART. Because of rapid progression in 2 of the first 5 patients, high-dose thiotepa was systematically adopted after HART in the subsequent 10 patients. Six of 15 patients relapsed (4 locally, 1 locally with dissemination, 1 with dissemination) a mean of 6 months after starting CT, 2 developed second tumors; 5 of 6 relapsers died at a median of 13 months. Three-year progression-free survival, event-free survival, and overall survival were 54%, 34%, and 61%, respectively.


CONCLUSIONS
Hyperfractionated accelerated RT was the main tool in obtaining responses in S-PNET; introducing the myeloablative phase improved the prognosis (3/10 vs. 3/5 relapses), though the outcome remained unsatisfactory despite the adoption of this intensive treatment.
Massimino
Maura
M
Neuro-Oncology Functional Unit, Department of Pediatric Oncology, Istituto Nazionale Tumori, Milan, Italy. maura.massimino@istitutotumori.mi.it
Gandola
Lorenza
L
Spreafico
Filippo
F
Luksch
Roberto
R
Collini
Paola
P
Giangaspero
Felice
F
Simonetti
Fabio
F
Casanova
Michela
M
Cefalo
Graziella
G
Pignoli
Emanuele
E
Ferrari
Andrea
A
Terenziani
Monica
M
Podda
Marta
M
Meazza
Cristina
C
Polastri
Daniela
D
Poggi
Geraldina
G
Ravagnani
Fernando
F
Fossati-Bellani
Franca
F
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage; D019583:Dose Fractionation, Radiation; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008130:Lomustine / Q000008:administration & dosage; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D018242:Neuroectodermal Tumors, Primitive / Q000188:drug therapy* / Q000532:radiotherapy*; D011446:Prospective Studies; D033581:Stem Cell Transplantation / Q000379:methods; D015173:Supratentorial Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D016019:Survival Analysis; D013852:Thiotepa / Q000008:administration & dosage; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
D014750:Vincristine; D005047:Etoposide; D008130:Lomustine; D003520:Cyclophosphamide; D013852:Thiotepa; D016190:Carboplatin; D008727:Methotrexate