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Stage 4S Neuroblastoma: What Are the Outcomes? A Systematic Review of Published Studies
Introduction The prognosis of stage 4S/MS neuroblastoma has traditionally been reported as excellent, yet conflicting treatment protocols exist for this enigmatic disease. To critically address this question, we have undertaken a systematic review of published studies to accurately determine outcomes for infants with stage 4S/MS neuroblastoma.
Materials and Methods Studies were identified using MEDLINE, Embase, and Cochrane databases using the relevant search terms. Literature reviews, case reports, and adult studies were excluded. Data were extracted independently following article selection by three authors and reviewed by the senior author.
Results The original search retrieved 2,325 articles. Following application of exclusion criteria and removing duplicate data, 37 studies (1,105 patients) were included for final review. Overall patient survival was 84%. Twelve studies (544 patients) recorded MYCN status. Mortality in MYCN amplified tumors was 56%. Chromosome 1p/11q status was reported in four studies and 1p/11q deletion carried a 40% fatality rate. Management included observation only (201 patients, 8.5% mortality), surgical resection of primary tumor only (153 patients, 6.5% mortality), chemotherapy only (186 patients, 21% mortality), radiotherapy (5 deaths, 33% mortality), chemotherapy with surgery (160 patients, 10% mortality), surgery with radiotherapy (21 patients, 19% mortality), radiotherapy with chemotherapy (42 patients, 29% mortality), and surgery with chemotherapy and radiotherapy (27 patients, 33% mortality).
Conclusion There is a significant mortality observed in stage 4S/MS neuroblastoma infants with a dismal outcome observed in those patients with MYCN amplification and 1p/11q deletion. Those patients suitably amenable for conservative management or surgery to excise the primary tumor carry the best prognosis.
Received: 29 June 2020
Accepted: 16 August 2020
15 September 2020 (online)
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- 1 D'Angio GJ, Evans AE, Koop CE. Special pattern of widespread neuroblastoma with a favourable prognosis. Lancet 1971; 1 (7708): 1046-1049
- 2 Cohn SL, Pearson AD, London WB. INRG Task Force. et al; The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report. J Clin Oncol 2009; 27 (02) 289-297
- 3 Monclair T, Brodeur GM, Ambros PF. INRG Task Force. et al; The International Neuroblastoma Risk Group (INRG) staging system: an INRG Task Force report. J Clin Oncol 2009; 27 (02) 298-303
- 4 Brodeur GM. Spontaneous regression of neuroblastoma. Cell Tissue Res 2018; 372 (02) 277-286
- 5 Koivusalo AI, Pakarinen MP, Rintala RJ, Saarinen-Pihkala UM. Surgical treatment of neuroblastoma: twenty-three years of experience at a single institution. Surg Today 2014; 44 (03) 517-525
- 6 Moreno F, Lopez Marti J, Palladino M, Lobos P, Gualtieri A, Cacciavillano W. Childhood neuroblastoma: incidence and survival in Argentina. Report from the National Pediatric Cancer Registry, ROHA Network 2000-2012. Pediatr Blood Cancer 2016; 63 (08) 1362-1367
- 7 Youlden DR, Frazier AL, Gupta S. et al Stage at diagnosis for childhood solid cancers in Australia: a population-based study. Cancer Epidemiol 2019; 59: 208-214
- 8 De Bernardi B, Di Cataldo A, Garaventa A. et al Stage 4 s neuroblastoma: features, management and outcome of 268 cases from the Italian Neuroblastoma Registry. Ital J Pediatr 2019; 45 (01) 8
- 9 Salim A, Mullassery D, Pizer B, McDowell HP, Losty PD. Neuroblastoma: a 20-year experience in a UK regional centre. Pediatr Blood Cancer 2011; 57 (07) 1254-1260
- 10 De Bernardi B, Pianca C, Boni L. Italian Cooperative Group on Neuroblastoma. et al; Disseminated neuroblastoma (stage IV and IV-S) in the first year of life. Outcome related to age and stage. Cancer 1992; 70 (06) 1625-1633
- 11 Katzenstein HM, Bowman LC, Brodeur GM. et al Prognostic significance of age, MYCN oncogene amplification, tumor cell ploidy, and histology in 110 infants with stage D(S) neuroblastoma: the pediatric oncology group experience--a pediatric oncology group study. J Clin Oncol 1998; 16 (06) 2007-2017
- 12 Hsu LL, Evans AE, D'Angio GJ. Hepatomegaly in neuroblastoma stage 4s: criteria for treatment of the vulnerable neonate. Med Pediatr Oncol 1996; 27 (06) 521-528
- 13 Schleiermacher G, Rubie H, Hartmann O. Neuroblastoma Study Group of the French Society of Paediatric Oncology. et al; Treatment of stage 4s neuroblastoma--report of 10 years' experience of the French Society of Paediatric Oncology (SFOP). Br J Cancer 2003; 89 (03) 470-476
- 14 Moher D, Liberati A, Tetzlaff J, Altman DG. PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement. BMJ 2009; 339: b2535
- 15 De Bernardi B, Gerrard M, Boni L. et al Excellent outcome with reduced treatment for infants with disseminated neuroblastoma without MYCN gene amplification. J Clin Oncol 2009; 27 (07) 1034-1040
- 16 Fischer M, Oberthuer A, Brors B. et al Differential expression of neuronal genes defines subtypes of disseminated neuroblastoma with favorable and unfavorable outcome. Clin Cancer Res 2006; 12 (17) 5118-5128
- 17 Nickerson HJ, Matthay KK, Seeger RC. et al Favorable biology and outcome of stage IV-S neuroblastoma with supportive care or minimal therapy: a Children's Cancer Group study. J Clin Oncol 2000; 18 (03) 477-486
- 18 Fawzy M, El Zomor H, El Menawi S. et al Watch and see strategy in selected neuroblastoma case scenarios: success and limitations. J Pediatr Hematol Oncol 2019; 41 (06) e384-e387
- 19 de Bouyn-Icher C, Minard-Colin V, Isapof A, Khuong Quang DA, Redon I, Hartmann O. Malignant solid tumors in neonates: a study of 71 cases [in French]. Arch Pediatr 2006; 13 (12) 1486-1494
- 20 Wang Z, Sun H, Li K. et al Prognostic factor analysis of stage 4S neuroblastoma in infant patients: a single center study. J Pediatr Surg 2019; 54 (12) 2585-2588
- 21 Weintraub M, Waldman E, Koplewitz B. et al A sequential treatment algorithm for infants with stage 4s neuroblastoma and massive hepatomegaly. Pediatr Blood Cancer 2012; 59 (01) 182-184
- 22 Salim A, Raitio A, Mullassery D, Pizer B, Losty PD. Neuroblastoma: The Association of Anatomical Tumour Site, Molecular Biology and Patient Outcomes. Eur J Ped Surg (submitted) 2020
- 23 Stokes SH, Thomas PR, Perez CA, Vietti TJ. Stage IV-S neuroblastoma. Results with definitive therapy. Cancer 1984; 53 (10) 2083-2086