Treatment and outcome of adult‐onset neuroblastoma

Abstract

Adult-onset neuroblastoma is rare and little is known about its biology and clinical course. There is no established therapy for adult-onset neuroblastoma. Anti-GD2 immunotherapy is now standard therapy in children with high-risk neuroblastoma; however, its use has not been reported in adults. Forty-four adults (18-71 years old) diagnosed with neuroblastoma between 1979 and 2015 were treated at Memorial Sloan Kettering Cancer Center. Five, 1, 5 and 33 patients had INSS stage 1, 2, 3 and 4 diseases, respectively. Genetic abnormalities included somatic ATRX (58%) and ALK mutations (42%) but not MYCN-amplification. In the 11 patients with locoregional disease, 10-year progression-free (PFS) and overall survival (OS) was 35.4 ± 16.1% and 61.4 ± 15.3%, respectively. Among 33 adults with stage 4 neuroblastoma, 7 (21%) achieved complete response (CR) after induction chemotherapy and/or surgery. Seven patients with primary refractory neuroblastoma (all with osteomedullary but no soft tissue disease) received anti-GD2 antibodies, mouse or humanized 3F8. Antibody-related adverse events were similar to those in children, response rate being 71.4%. In patients with stage 4 disease at diagnosis, 5-year PFS was 9.7± 5.3% and most patients who were alive with disease at 5 years died of neuroblastoma over the next 5 years, 10-year OS being only 19.0 ± 8.2%. Patients who achieved CR after induction had superior PFS and OS (p = 0.006, p = 0.031, respectively). Adult-onset neuroblastoma appeared to have different biology from pediatric or adolescent NB, and poorer outcome. Complete disease control appeared to improve long-term survival. Anti-GD2 immunotherapy was well tolerated and might be beneficial.

Adult‐onset neuroblastoma: Report of seven cases with molecular genetic characterization

“…Only a few studies have looked at ATRX mutations in adult‐onset neuroblastoma. By sequencing, mutations were detected in 19/32 cases altogether (59%) in keeping with the concept that mutations in ATRX are most frequent in older patients. Only one study carried out ALT assessment by FISH and found 3/3 cases with ATRX mutations also showed ALT by FISH .…”

“…The best documented difference is the increased frequency of ATRX mutations in adult cases . Such patients have protracted courses and do not respond as well to standard chemotherapy . The finding that 80% of our cases tested showed genetic changes in keeping with telomere maintenance provides a molecular confirmation of the high‐risk biology of adult neuroblastoma.…”

“…Most studies have limited or no molecular genetic data, but have concluded that adult patients have a poorer outcome compared to children although not all studies have found this to be the case . It has been proposed that poorer survival is related to differences in tumor biology . The main purpose of our study was to examine cases of adult‐onset neuroblastoma for a series of molecular genetic changes that are known to carry a negative effect on tumor biology in pediatric neuroblastoma.…”

High-dose chemotherapy with autologous hematopoietic stem cell transplantation in high-risk neuroblastoma patients: Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, First Pavlov State Medical University of St. Petersburg experience

“…Так, в группе пациентов старше 5 лет на момент постановки диагноза крайне редко встречается амплификация MYCN, но сравнительно чаще наблюдается первичная резистентность. Учитывая биологическую гетерогенность заболевания [17], различное клиническое течение и ответ на терапию в разных возрастных группах, пациенты более старшего возраста могут требовать дифференцированного подхода к терапии [18].…”

Adult neuroblastoma: a rare diagnosis of an adrenal mass

“…The treatment for childhood neuroblastoma is well established and involves a multimodality approach consisting mainly of chemotherapy, radiotherapy and surgery; however, there is no well-established treatment algorithm for adults. New studies have suggested that treatment with anti-GD2 immunotherapy may improve survival but larger randomised controlled studies are required in adults 7…”