Outcomes of children with intermediate-risk neuroblastoma after treatment stratified by MYCN status and tumor cell ploidy.
OBJECTIVE
The goal of Pediatric Oncology Group 9243 was to improve outcomes for children with intermediate-risk neuroblastoma (NB).


METHODS
Patients were assigned to treatments on the basis of age, tumor MYCN status, and tumor cell ploidy. Children in the less intensive arm A received cyclophosphamide/doxorubicin and surgery. Patients not in complete remission postoperatively were treated with cisplatin/etoposide, cyclophosphamide/doxorubicin, and additional surgery. Patients with less favorable features were assigned to arm B, which consisted of carboplatin, etoposide, ifosfamide, and surgery. Survival rates were determined using an intent-to-treat approach.


RESULTS
For arm-A patients, the 6-year event-free survival (EFS) was 86% with an SE of 3%. For arm-B patients, the 6-year EFS was 46% with an SE of 7%. MYCN status was the only statistically significant prognostic variable. Among patients whose tumors were MYCN nonamplified, a trend toward improved EFS was seen in children with hyperdiploid versus diploid tumors. However, many of these children responded well to salvage therapy, and overall survival rates did not differ on the basis of ploidy. Six-year EFS rates for arm B were patients with MYCN nonamplified, hyperdiploid tumors, 86% with an SE of 3%; patients with MYCN nonamplified, diploid tumors, 74% with an SE of 10%; patients with MYCN-amplified, hyperdiploid tumors, 46% with an SE of 15%; and patients with MYCN-amplified, diploid tumors, 22% with an SE of 10%.


CONCLUSIONS
Outcomes for patients with MYCN-nonamplified, hyperdiploid tumors were excellent. Therapy reductions for these patients merit study. A trend toward less favorable outcomes for patients with MYCN-nonamplified, diploid tumors was observed; more children may need to be evaluated before therapy is reduced for this subgroup. For patients with MYCN-amplified tumors, new strategies are needed.
Bagatell
Rochelle
R
University of Arizona, Department of Pediatrics and Steele Children's Research Center, Tuscon, AZ, USA. bagatell@peds.arizona.edu
Rumcheva
Pavlina
P
London
Wendy B
WB
Cohn
Susan L
SL
Look
A Thomas
AT
Brodeur
Garrett M
GM
Frantz
Christopher
C
Joshi
Vijay
V
Thorner
Paul
P
Rao
P V
PV
Castleberry
Robert
R
Bowman
Laura C
LC
D000008:Abdominal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D007223:Infant; D008297:Male; D000071447:N-Myc Proto-Oncogene Protein; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009503:Neutropenia / Q000139:chemically induced; D009687:Nuclear Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D011003:Ploidies; D011379:Prognosis; D012307:Risk Factors; D016896:Treatment Outcome
C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D016190:Carboplatin; D002945:Cisplatin; D007069:Ifosfamide