Unresectable localized neuroblastoma: improved survival after primary chemotherapy including carboplatin-etoposide

Abstract

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)

High‐dose chemotherapy followed by locoregional irradiation improves the outcome of patients with international neuroblastoma staging system Stage II and III neuroblastoma with MYCN amplification

“…[7][8][9] Conversely, MNA, which accounts for 7-12% 5,7 of localized NB, is well known as a strong predictor of poor outcome in patients with Stage II 4,5,10 or Stage III 4,5,[7][8][9]11 NB, with survival rates Ͻ 30%. These patients can experience rapid local and/or metastatic disease recurrence, 4,5,9 with all or most recurrences resulting in death.…”

The LMCE5 unselected cohort of 25 children consecutively diagnosed with untreated stage 4 neuroblastoma over 1 year at diagnosis

“…Much cooperative work has been done in France, between surgeons, radiologists and oncologists, to predict surgical difficulties in localised neuroblastomas (Rubie et al, 1998). This has also probably improved surgical management in metastatic disease and explains the low rate of nephrectomy (four out of 20 abdominal procedures).…”

Criteria for evaluation of disease extent by 123I-metaiodobenzylguanidine scans in neuroblastoma: a report for the International Neuroblastoma Risk Group (INRG) Task Force

“…Intermediate-and low-risk patients should have mIBG scans at diagnosis, end of therapy and as surveillance at 6-month intervals until 1 year for low-risk stage 2 and 2 years after therapy for intermediate-risk patients. Although low-and intermediate-risk neuroblastoma have an excellent overall survival 490%, the event-free survival is only approximately 80% for stage 2 (Perez et al, 2000), stage 3 (Rubie et al, 1998), stage 4 and unfavourable biology 4 s (Nickerson et al, 2000;Schmidt et al, 2000;Hero et al, 2008;De Bernardi et al, 2009), suggesting that this modest surveillance schedule is reasonable to detect relapsing patients.…”