Loss of chromosome 1p may have a prognostic value in localised neuroblastoma: results of the French NBL 90 Study. Neuroblastoma Study Group of the Société Française d'Oncologie Pédiatrique (SFOP).
Between March 1990 and December 1994, 316 consecutive children with localised neuroblastoma were registered in the French NBL 90 study. In addition to the assessment of a new chemotherapy regimen in unresectable neuroblastoma, we evaluated the prognostic significance of MYCN amplification and loss of the short arm of chromosome 1 (LOH1p). MYCN was found in 22/225 children (10%) and associated with unfavourable clinical features such as age at diagnosis > 1 year and large and unresectable tumours. LOH1p was observed in 9/91 patients (10%), of whom some had favourable prognostic factors such as age at diagnosis < 1 year (n = 4), INSS stage 1 or 2 (n = 3) and no MYCN amplification (n = 4). Overall survival (OS) and event-free survival (EFS) were, respectively, 56% and 22% (median follow-up: 36 months) for children with LOH1p compared with 97% and 94% for those without (log-rank = 10(-8)). All except 1 of the 5 children with MYCN amplification and LOH1p relapsed and ultimately died of the disease. Among the 4 with LOH1p and no MYCN amplification, recurrence occurred in 3 (2 local, 1 metastatic), all alive in second remission after salvage therapy (12-19 months after the relapse). In multivariate analysis, LOH1p was the strongest prognostic indicator for subsequent relapse. LOH1p appears more discriminant than MYCN amplification for predicting the risk of recurrence in children with localised neuroblastoma. However, its analysis was possible in only 30% of our patients and its final impact on survival should be confirmed in larger, prospective studies in order to stratify subsequent treatment.
Rubie
H
H
Unité d'Oncologie Pédiatrique, CHU Purpan, Toulouse, France.
Delattre
O
O
Hartmann
O
O
Combaret
V
V
Michon
J
J
Bénard
J
J
Peyroulet
M C
MC
Plantaz
D
D
Coze
C
C
Chastagner
P
P
Baranzelli
M C
MC
Frappaz
D
D
Lemerle
J
J
Sommelet
D
D
D000008:Abdominal Neoplasms / Q000235:genetics* / Q000473:pathology; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification; D016259:Genes, myc / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D016019:Survival Analysis