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

Abstract

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.

Congenital abdominal wall defects and cryptorchidism: a population-based study

“…Abdominal wall defects (AWDs), notably gastroschisis and omphalocele, are relatively rare congenital anomalies with a prevalence of 1.85 and 1.96 per 10,000 births in Finland, respectively [ 1 , 2 ]. Total prevalence of these anomalies has increased in Finland since previous rates published in 1980s [ 3 ].…”

“…Total prevalence of these anomalies has increased in Finland since previous rates published in 1980s [ 3 ]. Due to over 50% termination rate for omphalocele, however, increased live birth prevalence has only been observed in gastroschisis [ 1 , 2 ]. In most cases, gastroschisis in an isolated anomaly [ 1 , 4 , 5 ], whereas omphalocele is often associated with other severe anomalies including chromosomal abnormalities and cardiac defects [ 2 , 6 , 7 ].…”

“…Due to over 50% termination rate for omphalocele, however, increased live birth prevalence has only been observed in gastroschisis [ 1 , 2 ]. In most cases, gastroschisis in an isolated anomaly [ 1 , 4 , 5 ], whereas omphalocele is often associated with other severe anomalies including chromosomal abnormalities and cardiac defects [ 2 , 6 , 7 ]. As both of these congenital malformations are life-threatening conditions at birth, it has been speculated that the prevalence of UDT among boys with AWD may be under-reported because of the greater emphasis on lethal comorbidities [ 8 ].…”

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

“…A recent systematic review on the outcome of stage 4S neuroblastoma confirmed that significant mortality is still observed in these patients, and that those with MYCN gene amplification and 1p/11q deletion have a dismal outcome [31]. The authors concluded that patients amenable to conservative management or surgery to excise the primary tumor have the best prognosis.…”

Neuroblastoma: the association of anatomical tumour site, molecular biology and patient outcomes

“…Amplification of MYCN oncoprotein is strongly associated with rapid disease progression and poor outcome in patients independent of age and tumour staging 4,5 . Other chromosomal aberrations associated with either whole DNA copy number alterations or incomplete segmental alterations have also been shown to predict NB behaviour.…”