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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.

SUBMITTER: Schleiermacher G

PROVIDER: S-EPMC2394373 | biostudies-other | 2003 Aug

REPOSITORIES: biostudies-other

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Project description:PurposeInfants with stage 4S neuroblastoma usually have favorable outcomes with observation or minimal chemotherapy. However, young infants with symptoms secondary to massive hepatomegaly or with unfavorable tumor biology are at high risk of death. Our aim was to improve outcomes for patients with symptomatic and/or unfavorable biology 4S neuroblastoma with a uniform treatment approach using a biology- and response-based algorithm.Patients and methodsThe subset of patients with 4S disease with MYCN-not amplified tumors with impaired or impending organ dysfunction, or with unfavorable histology and/or diploid DNA index, were eligible. Patients were assigned to receive two, four, or eight cycles of chemotherapy on the basis of histology, diploid DNA index, chromosome arm 1p or 11q loss of heterozygosity (LOH) status, and symptoms.ResultsForty-nine eligible patients were enrolled: 41 were symptomatic and 28 had unfavorable biology. Seventeen patients (symptomatic, favorable biology) were assigned two cycles, 21 patients (any unfavorable biologic feature without 1p or 11q LOH) were assigned four cycles, and 11 patients (unfavorable biology including 1p and/or 11q LOH [n = 7] or symptomatic with unknown biology [n = 4]), were assigned eight cycles. The 3-year overall survival was 81.4% ± 5.8%. Eight of nine deaths were in patients younger than 2 months of age at diagnosis (median, 9 days [range, 1 to 68 days]): five acute deaths were a result of hepatomegaly and associated toxicities; two were a result of late relapse in patients with unfavorable biology; and two were a result of treatment complications. No deaths occurred after protocol-mandated pre-emptive treatment of infants younger than 2 months with hepatomegaly, regardless of symptoms. A new scoring algorithm for emergent chemotherapy in patients with 4S disease was developed on the basis of this experience.ConclusionThe outcome for 4S neuroblastoma can be improved with pre-emptive chemotherapy for evolving hepatomegaly or other baseline comorbidities in infants younger than 2 months of age.

Project description:Background: The spontaneous regression of neuroblastoma (NB) is most prevalent and well-documented in stage 4s NB patients. However, whether autophagy plays roles in the spontaneous regression of NB is unknown. Objective: This study aimed to identify autophagy-related genes (ARGs) and autophagy-related long non-coding RNAs (lncRNAs) differentially expressed in stage 4 and stage 4s NB and to build prognostic risk signatures on the basis of the ARGs and autophagy-related lncRNAs. Methods: One RNA-sequence (RNA-Seq) dataset (TARGET NBL, n = 153) was utilized as discovery cohort, and two microarray datasets (n = 498 and n = 223) were used as validation cohorts. Differentially expressed ARGs were identified by comparing stage 4s and stage 4 NB samples. An ARG signature risk score and an autophagy-related lncRNA signature risk score were constructed. The receiver operating characteristic (ROC) curve analyses were used to evaluate the survival prediction ability of the two signatures. Gene function annotation and Gene Set Enrichment Analysis (GSEA) were performed to clarify the autophagic biological processes enriched in different risk groups. Results: Nine ARGs were integrated into the ARG signature. Patients in the high-risk group of the ARG signature had significantly poorer overall survival (OS) than patients in the low-risk group. The ROC curves analyses revealed that the ARG signature performed very well in predicting OS [5-year area under the curve (AUC) = 0.81]. Seven autophagy-related lncRNAs were integrated into the autophagy-related lncRNA signature. Patients in the high-risk group of the lncRNA signature had significantly poorer OS than patients in the low-risk group. The ROC curve analyses also revealed that the lncRNA signature performed well in predicting OS (5-year AUC = 0.77). Both the ARG signature and lncRNA signature are independent with other clinical risk factors in the multivariate Cox regression survival analyses. GSEAs revealed that autophagy-related biological processes are enriched in low-risk groups. Conclusions: Autophagy-related genes and lncRNAs are differentially expressed between stage 4 and stage 4s NB. The ARG signature and autophagy-related lncRNA signature successfully stratified NB patients into two risk groups. Autophagy-related biological processes are highly enriched in low-risk NB groups.

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

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