Intensive chemotherapy followed by consolidative myeloablative chemotherapy with autologous hematopoietic cell rescue (AuHCR) in young children with newly diagnosed supratentorial primitive neuroectodermal tumors (sPNETs): report of the Head Start I and II experience.
BACKGROUND
Children with newly diagnosed supratentorial primitive neuroectodermal tumors (sPNET) have poor outcomes compared to medulloblastoma patients, despite similar treatments. In an effort to improve overall survival (OS) and event-free survival (EFS) and to decrease radiation exposure, the Head Start (HS) protocols treated children with newly diagnosed sPNET utilizing intensified induction chemotherapy (ICHT) followed by consolidation with myeloablative chemotherapy and autologous hematopoietic cell rescue (AuHCR).


METHODS
Between 1991 and 2002, 43 children with sPNET were prospectively treated on two serial studies (HS I and II). After maximal safe surgical resection, patients on HS I and patients with localized disease on HS II were treated with five cycles of ICHT (vincristine, cisplatin, cyclophosphamide, and etoposide). Patients on HS II with disseminated disease received high-dose methotrexate during ICHT. If the disease remained stable or in response, patients received a single cycle of high-dose myeloablative chemotherapy followed by AuHCR.


RESULTS
Five-year EFS and OS were 39% (95%CI: 24%, 53%) and 49 (95%CI: 33%, 62%), respectively. Non-pineal sPNET patients faired significantly better than those patients with pineal sPNETs. Metastasis at diagnosis, age, and extent of resection were not significant prognostic factors. Sixty percent of survivors (12 of 20) are alive without exposure to radiation therapy.


CONCLUSIONS
ICHT followed by AuHCR in young patients with newly diagnosed sPNET appears to not only provide an improved EFS and OS for patients who typically have a poor prognosis, but also it successfully permitted deferral and elimination of radiation therapy in a significant proportion of patients.
Fangusaro
Jason
J
Children's Hospital Los Angeles, Los Angeles, California, USA. jfangusaro@childrensmemorial.org
Finlay
Jonathan
J
Sposto
Richard
R
Ji
Lingyun
L
Saly
Monirath
M
Zacharoulis
Stergios
S
Asgharzadeh
Shahab
S
Abromowitch
Minnie
M
Olshefski
Randal
R
Halpern
Steven
S
Dubowy
Ronald
R
Comito
Melanie
M
Diez
Blanca
B
Kellie
Stewart
S
Hukin
Juliette
J
Rosenblum
Marc
M
Dunkel
Ira
I
Miller
Douglas C
DC
Allen
Jeffrey
J
Gardner
Sharon
S
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D015080:Mesna / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage; D018242:Neuroectodermal Tumors, Primitive / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D015173:Supratentorial Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage
D016179:Granulocyte Colony-Stimulating Factor; D014750:Vincristine; D005047:Etoposide; D003520:Cyclophosphamide; D016190:Carboplatin; D015080:Mesna; D002945:Cisplatin; D008727:Methotrexate