Prognostic factors in metastatic neuroblastoma. A multivariate analysis of 182 cases.

The purpose of our study was to investigate the interrelationship of known and possible new risk factors in patients with metastatic neuroblastoma and to define groups at risk. The possible influence of 37 variables on event-free survival (EFS) was analyzed univariately in 308 consecutive patients using the Kaplan-Meier estimate. Fifteen factors were identified (p less than 0.05, logrank greater than 3.84) of whom eight showed a nonrandom correlation to several others (chi 2-test, p less than 0.05). Seven noncorrelated factors [lactate dehydrogenase (LDH) level, resectability of the primary tumor, histologic grade, leukopenia, presence of symptoms, general condition, and age at diagnosis] were included in the multivariate analysis of 182 patients according to the Cox model. The variables LDH (p = 0.0007), resectability (p = 0.0063), histologic grade (p = 0.0055), and leukopenia (p = 0.0470) were identified multivariately as prognostic factors for EFS. These results permitted the classification of patients into three prognostic groups. The 6 year event-free survival for group IV-A (LDH normal) was 0.37 +/- 0.12, for group IV-B (LDH abnormal, additional risk factors favorable) 0.18 +/- 0.10, and for group IV-C (LDH abnormal, 1-3 additional risk factors unfavorable) was 0.08 +/- 0.03. We conclude that the proposed clinicopathological classification may prove to be a reliable and easily applicable tool for estimating the outcome of metastatic neuroblastoma in children.

The role of chemotherapy in the treatment of children with neuroblastoma stage IV: the GPO (German Pediatric Oncology Society) experience.

340 consecutive patients with neuroblastoma stage IV were analyzed for the possible impact of chemotherapy on general condition, remission status, event free survival and survival. The children entered the trials NB 79, NB 82 and NB 85 of the German Pediatric Oncology Society (GPO). The patients did benefit from chemotherapy by considerable improvement of the general condition, by achievement of 30-40% complete and 60-70% partial remissions. The event free survival (EFS) rate 5-8 years after diagnosis was 13% for all 299 protocol patients, the survival (S) rate 10%. The median/mean EFS time were 11.6/23.8 months, the median/mean S time 17.0/29.4 months. The use of response rates as early predictors for long term survival is challenged. Addition of PCVm (cisplatinum, cyclophosphamide, Vm 26) to ACVD (adriamycine, cyclophosphamide, vincristine, dacarbazine) in trial NB 82 resulted in an improvement of the long term EFS rate from 5% to 18% (S rates 7----21%). The introduction of IVp (ifosfamide, VP16) and increase of doses (cisplatinum, Vm 26) did not further improve the results. Maintenance therapy (NB 82) revealed a positive influence on the outcome. Shorter intervals for realization of chemotherapy were associated with a trend for better EFS (NB 85). Although the group of children with bone marrow transplantation showed better EFS and S data compared to the unselected chemotherapy group, the advantage was less clear if matched pairs (remission status at the time of BMT) were compared.(ABSTRACT TRUNCATED AT 250 WORDS)

The impact of preoperative chemotherapy on resectability of primary tumour and complication rate in metastatic neuroblastoma.

231 children with metastatic neuroblastoma prospectively followed up in three clinical trials underwent first look surgery at diagnosis or delayed first look operation after application of chemotherapy and partly second look surgery and were evaluated for resectability and complication rate. More than 85% of the primary tumours were located within the abdomen. The incidence of macroscopically complete removal increased from 30% to 60% after preoperative chemotherapy (p less than 0.001). There was no difference between the efficacy of delayed first look and second look surgery and between children with stage IV and stage IV S neuroblastoma. The mean complication rate was 20% (complication per patient) and 23% (complication per operation). Complications included local problems (7.9%), infections (5.9%), organ dysfunctions (8.3%) and rare other complications (1.3%). No significant difference was found between the three surgical modalities, i.e. preoperative chemotherapy did neither increase the complication rate nor change the complication pattern. The biological meaning of primary tumour control is still unclear. However, a 40% local recurrence rate suggests an aggressive surgical attitude. Our study provides a basis that preoperative chemotherapy may be an effective tool to achieve complete removal of initially non-resectable primary tumours without increasing the complication rate.