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Annals of Oncology 13:956-964, 2002
© 2002 European Society for Medical Oncology

Original Paper

Localized unresectable neuroblastoma: results of treatment based on clinical prognostic factors

A. Garaventa1,+, L. Boni2, M. S. Lo Piccolo1, G. P. Tonini3, C. Gambini4, A. Mancini6, L. Tonegatti6, M. Carli6, L. C. di Montezemolo6, A. Di Cataldo6, F. Casale6, K. Mazzocco3, G. Cecchetto6, A. Rizzo5 and B. De Bernardi1,§

Departments of 1Hematology–Oncology, 6Surgery and 4Pathology, Giannina Gaslini Children’s Hospital, Genova; 2Epidemiology and Clinical Trials Unit and 3Laboratory of Population Genetics, National Institute for Cancer Research, Genova; 5Departments of Pediatrics and Pediatric Surgery, Universities of Padova, Bologna, Napoli, Torino, Brescia, and Catania, Italy

Received 3 July 2001; revised and accepted 15 January 2002.

Background

We previously reported that stage 3 neuroblastoma comprises (i) a low-risk group including all infants (age 0–11 months) as well as older children with non-abdominal primaries, and (ii) a high-risk group made up of children >1 year of age with abdominal primaries. Aggressive chemotherapy was effective only in the latter group.

Patients and treatment

On this basis, in 1990 we designed a new protocol by which all low-risk patients received standard-dose chemotherapy, while the high-risk ones received very aggressive chemotherapy.

Results

Between November 1990 and December 1997 a total of 95 eligible and evaluable children were enrolled: 47 were low-risk (35 infants and 12 >1 year of age at diagnosis and having non-abdominal primaries), and 48 were high-risk (being >1 year of age and having abdominal primaries). Of the 47 low-risk patients, five relapsed and four subsequently died. The 5-year overall survival (OS) was 91%. Of the 48 patients in the high-risk group, 22 relapsed or progressed, 18 of whom died from their disease and two from toxicity, and one was lost to follow-up. The 5-year OS was 60%. Univariate analysis showed that age, site of primary, risk-group, urine vanillylmandelic excretion, plasma levels of lactate dehydrogenase, ferritin and neurone-specific enolase, and MYCN status correlated with outcome. However, multivariate analysis showed that only MYCN status retained prognostic value.

Conclusions

In low-risk stage 3 neuroblastoma, standard-dose chemotherapy is associated with an excellent chance of being cured. Aggressive chemotherapy is effective for high-risk patients, but results are still unsatisfactory. MYCN gene amplification is a prognostic indicator for most, but not all, treatment failures.

Key words: prognostic factors, treatment, unresectable neuroblastoma


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