Our data confirm the overall good prognosis of localized NBs, even when unresectable. NMA is the most relevant adverse prognostic factor in localized NBs, and more intensive treatment should be investigated in these patients. Prospective studies of other biologic factors are warranted to tailor therapy more accurately. The EFS of children who underwent primary surgery was excellent, and further justifies elimination of adjuvant treatment provided they have no NMA. Despite the elimination of postoperative therapy, infants with non-NMA tumors have an excellent outcome, which suggests that initial chemotherapy can be further reduced in case of unresectable NBs.

We conducted a prospective study of respiratory function in children undergoing bone marrow transplantation (BMT) for onco‐hematological disorders. Each child was evaluated before and 100 days after BMT. The investigations included clinical examination, chest X‐ray, and pulmonary function tests (PFT) to determine: slow vital capacity (VC), functional residual capacity (FRC), total lung capacity (TLC), forced expiratory volume in 1 s (FEV1), carbon monoxide diffusing capacity (DLCO), ratio of residual volume (RV) to TLC, and FEV1/VC. The values obtained before and after BMT were compared to predicted values, and the post‐BMT values were compared to the pre‐BMT values (Student's t‐test). From 1986 to 1995, 77 children underwent BMT, of whom 39 were available for testing. The pre‐BMT VC (P = 0.0234) and DLCO (P < 0.0001) were lower and FRC higher (P < 0.0001) than predicted values. After BMT, the VC (P = 0.004), TLC (P = 0.044), and FEV1 (P = 0.012) were lower, and the RV/TLC ratio was higher (P = 0.043), compared with pre‐BMT data. The observed respiratory abnormalities were not clinically relevant. The only identifiable risk factor for a decrease in lung function was age at BMT. This study shows that some lung dysfunction may be present before BMT and be further altered by BMT. This stresses the need for longitudinal respiratory monitoring and follow up to detect such dysfunctions and to insure an optimal treatment program for these children. Pediatr Pulmonol. 1999; 28:31–38. © 1999 Wiley‐Liss, Inc.

To assess the relevance of MYCN amplification and bone lesions in stage 4 neuroblastoma (NB) in infants aged <1 year, 51 infants with stage 4 NB were enrolled. Three groups of patients were defined according to the type of metastases and the resectability of the primary tumour. Group I comprised 21 infants with radiologically detectable bone lesions, Group II 22 patients with an unresectable primary tumour and Group III eight patients with only metaiodobenzylguanidine (MIBG) skeletal uptake. MYCN oncogene content was assayed in 47/51 tumours and found to be amplified in 17 (37%). The 5-year event-free survival (EFS) rate of these 51 infants was 64.1% (± 7.1%). In a univariate analysis, bone lesions, MYCN amplification, urinary vanillylmandelic/homovanillic acid ratio and serum ferritin levels adversely influenced outcome. In the multivariate analysis, radiologically detectable bone lesions were the most powerful unfavourable prognostic indicator: the EFS rate was 27.2% for these infants compared to 90% for infants without bone lesions (P < 0.0001). Our data emphasize the poor prognosis of infants affected by stage 4 NB with bone lesions, especially when associated with MYCN amplification. Given the poor results in this group whatever the treatment, new therapeutic approaches need to be investigated in the future. © 2000 Cancer Research Campaign

Keywords: neuroblastoma; carboplatin; etoposide; N-myc Neuroblastoma (NB) is the most common solid tumour of early childhood (Bernstein et al, 1992). Approximately 50% of patients present with localized tumours (Hartmann et al, 1983;Rosen et al, 1984a) and radical surgical excision is generally considered as the main requirement for cure (Evans et al, 1976; Le Toumeau et al, 1985). Primary surgery can be performed in about half of these children and reported survival rates are high (De Bernardi et al, 1995). However, unresectable tumours usually have a poorer outcome, unless secondary radical excision can be performed (Rosen et al, 1984b;Haase et al, 1989;Tsuchida et al, 1992). Consequently, the efficacy of primary chemotherapy to allow subsequent resection is of outstanding importance (Garaventa et al, 1993; West et al, 1993). We previously reported the efficacy of the combination of carboplatin and etoposide (CE) in refractory or relapsed NBs (Frappaz et al, 1992) and investigated its relevance as a first line therapy in unresectable NBs.In 1990, a national prospective study (NBL 90) was initiated, registering all children with localized NBs diagnosed in the institutions of the French Society of Pediatric Oncology (SFOP). The Primary aim was to assess the efficacy and the safety of such chemotherapy as primary treatment in unresectable NBs, PATIENTS AND METHODS Patient populationUntreated children aged from 0 to 16 years were eligible. The primary tumour was evaluated using computerized tomography (CT)-scan or magnetic resonance imaging (MRI) as well as metaiodobenzylguanidine (MIBG) scintigraphy. Work-up to eliminate metastatic spread included the skeletal study by MIBG (or a 99mTc scan in the absence of MIBG uptake at the primary site), radiograph in infants and extensive bone marrow staging (at least two aspirations and two trephine biopsies). Urinary catecholamines (VMA, HVA and dopamine), serum neuron-specific enolase (NSE), ferritin and lactate dehydrogenase (LDH) levels were measured. The diagnosis of NB was always confirmed by cytological or histological documentation. The primary tumour was staged according to TNM (Beahrs, 1983) and INSS (Brodeur et al, 1993). However, those unresectable NBs did not overlap completely with INSS stage 3 tumours. Indeed, according to our definition of resectability using radiological data, those tumours were not operated first and some of them were INSS stage 2 (i.e. lateral tumours encasing regional organs or vessels and dumbbell tumours). Analysis of the N-myc oncogene (Seeger et al, 1985)

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