Treatment of stage 4s neuroblastoma--report of 10 years' experience of the French Society of Paediatric Oncology (SFOP)

Abstract

Stage 4s neuroblastoma (NB) is usually associated with a favourable outcome, despite a large tumour burden, as spontaneous regression frequently occurs. However, in some infants rapid disease progression can be observed with severe functional impairment. Thus, for all patients the potential risks of cytotoxic therapy must be weighed against the benefits of early medical intervention. We have retrospectively reviewed the charts of 94 infants treated for stage 4s NB in centres of the French Society of Paediatric Oncology between 1990 and 2000, and describe the different first-line treatment approaches that were, successively, liver irradiation, chemotherapy using a cyclophosphamide-vincristine regimen, and chemotherapy using a carboplatin-etoposide regimen. The overall survival was 88% (+/-7.6%), with a mean follow-up of 64 months. Elevated serum neuron-specific enolase (>100 nmol ml(-1)), ferritin (>280 ng ml(-1)) and urinary dopamine levels (>2500 nmol mmol(-1) creatinine) were associated with a poor outcome, as were the genetic markers N-myc amplification and chromosome 1p deletion (P<0.0005 and P=0.0016, respectively). Patients who required medical intervention at diagnosis fared worse than those who received supportive treatment only (P<0.005). The clinical evolution observed with the different successive treatment approaches suggests that if infants do require therapy, the prompt initiation of a more intensive regimen such as carboplatin-etoposide may be more beneficial.

Figure 1

First- and second-line treatment of 94 patients with stage 4 s neuroblastoma, and outcome. CO-cyclophosphamide–vincristine regimen; CE-carboplatin–etoposide regimen. DOD/DOT-dead of disease/dead of toxicity. CR/PR-complete/partial remission.

Figure 2

(A) Overall survival (OS) of 94 children with stage 4 s neuroblastoma. At 3-year OS (±2SE) was 88% (±7.6). (B) OS of 62 infants younger than 3 months at diagnosis, vs 32 infants older than 3 months at diagnosis. At 3-year OS (±2 s.e.) was 83% (±12.2) and 93% (±8) in children younger and older than 3 months, respectively (P<0.06, log-rank test). (C) OS of 37 asymptomatic infants at diagnosis, vs 57 infants who required treatment. At 3-year OS (±2 s.e.) was 100 and 80% (±11.8) for those who did not and those who did require treatment, respectively (P<0.005, log-rank test).