Stage 4 s neuroblastoma: features, management and outcome of 268 cases from the Italian Neuroblastoma Registry

Abstract

BackgroundInfants diagnosed with stage 4 s neuroblastoma commonly experience spontaneous disease regression, with few succumbing without response to therapy. We analyzed a large cohort of such infants enrolled in the Italian Neuroblastoma Registry to detect changes over time in presenting features, treatment and outcome.MethodsOf 3355 subjects aged 0–18 years with previously untreated neuroblastoma diagnosed between 1979 and 2013, a total of 280 infants (8.3%) had stage 4 s characteristics, 268 of whom were eligible for analyses. Three treatment eras were identified on the basis of based diagnostic and chemotherapy adopted. Group 1 patients received upfront chemotherapy; Group 2 and 3 patients underwent observation in the absence of life-threatening symptoms (LTS), except for Group 3 patients with amplified MYCN gene, who received more aggressive therapy.ResultsThe three groups were comparable, with few exceptions. Ten-year overall survival significantly increased from 76.9 to 89.7% and was worse for male gender, age 0–29 days and presence of selected LTS on diagnosis, elevated LDH, and abnormal biologic features. Infants who underwent primary resection ± chemotherapy did significantly better. On multivariate analysis, treatment eras and the association of hepatomegaly to dyspnea were independently associated with worse outcome.ConclusionsOur data confirm that stage 4 s neuroblastoma is curable in nearly 90% of cases. Hepatomegaly associated to dyspnea was the most important independent risk factor. The cure rate could be further increased through timely identification of patients at risk who might benefit from surgical techniques, such as intra-arterial chemoembolization and/or liver transplantation, which must be carried out in institutions with specific expertise.Electronic supplementary materialThe online version of this article (10.1186/s13052-018-0599-1) contains supplementary material, which is available to authorized users.

Stage 4S Neuroblastoma: What Are the Outcomes? A Systematic Review of Published Studies

“…4 Here, most tumors can be treated with active observation only with modest outcome(s) anticipated including stage 4S (INRG stage MS) neuroblastoma mortality ranging from 0 to 19%. 8,[15][16][17][18] Surgery with or without chemotherapy yielded excellent outcome(s) in stage 4S (INRG stage MS) neuroblastoma according to the quality of published literature reviewed here in this systematic review. Patients suitable for surgical resection of the offending primary tumor only had the best outcome(s).…”

“…Patients suitable for surgical resection of the offending primary tumor only had the best outcome(s). 8,11,15,17 Those requiring neoadjuvant chemotherapy before definitive surgical resection had also good outcomes with only 10% mortality. 11,15,19,20 Interestingly, those treated with surgical resection and radiotherapy with or without chemotherapy likely "scaled up" to control fulminant liver metastases had significantly worse outcome(s).…”

“…However, optimal treatment strategies and their outcomes still remain poorly understood. 8 Against this background, the aim of this systematic review study was to accurately better define clinical outcomes of infants with stage 4S (stage MS) neuroblastoma taking into account the different treatment modalities employed with the biological features of this enigmatic neuroblastic tumor.…”

The Over-Expression of E2F3 Might Serve as Prognostic Marker for Neuroblastoma Patients with Stage 4S Disease

“…We recovered a multi-institution retrospective series of primary NB tissue sections from 38 patients with stage 4S disease, diagnosed in the period from December 2000 to October 2011 in 27 centers of the Italian Association of Pediatric Hematology and Oncology (AIEOP) [44]…”

Resection of primary tumor in stage 4S neuroblastoma: a second study by the Italian Neuroblastoma Group

“…Its natural history is characterized by a period of tumor progression (lasting from a few days to some months) that may lead to death regardless of therapy, or be followed by therapy-induced or spontaneous regression [2], the mechanism of which is not fully understood [3]. The probability of cure is fairly high and has increased from 60% in the1980s [4][5][6][7] to the present 90% [8][9][10][11][12].…”