title: Factors associated with recurrence and survival length following relapse in patients with neuroblastoma.
abstract: BACKGROUND
  Despite therapeutic advances, survival following relapse for neuroblastoma patients remains poor. We investigated clinical and biological factors associated with length of progression-free and overall survival following relapse in UK neuroblastoma patients.
  
  
  METHODS
  All cases of relapsed neuroblastoma, diagnosed during 1990-2010, were identified from four Paediatric Oncology principal treatment centres. Kaplan-Meier and Cox regression analyses were used to calculate post-relapse overall survival (PROS), post-relapse progression-free survival (PRPFS) between relapse and further progression, and to investigate influencing factors.
  
  
  RESULTS
  One hundred eighty-nine cases were identified from case notes, 159 (84.0%) high risk and 17 (9.0%), unresectable, MYCN non-amplified (non-MNA) intermediate risk (IR). For high-risk patients diagnosed >2000, median PROS was 8.4 months (interquartile range (IQR)=3.0-17.4) and median PRPFS was 4.7 months (IQR=2.1-7.1). For IR, unresectable non-MNA patients, median PROS was 11.8 months (IQR 9.0-51.6) and 5-year PROS was 24% (95% CI 7-45%). MYCN amplified (MNA) disease and bone marrow metastases at diagnosis were independently associated with worse PROS for high-risk cases. Eighty percent of high-risk relapses occurred within 2 years of diagnosis compared with 50% of unresectable non-MNA IR disease.
  
  
  CONCLUSIONS
  Patients with relapsed HR neuroblastomas should be treatment stratified according to MYCN status and PRPFS should be the primary endpoint in early phase clinical trials. The failure to salvage the majority of IR neuroblastoma is concerning, supporting investigation of intensification of upfront treatment regimens in this group to determine whether their use would diminish likelihood of relapse.
authors.affiliation: Institute of Health & Society, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Nermine O
authors.initials: NO
authors.lastname: Basta
authors.affiliation: Newcastle Cancer Centre at the Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.|Department of Paediatric Oncology, The Great North Children's Hospital, Newcastle upon Tyne, UK.
authors.forename: Gail C
authors.initials: GC
authors.lastname: Halliday
authors.affiliation: Institute of Cancer Sciences, Manchester Cancer Research Centre, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.|Department of Paediatric Oncology, Royal Manchester Children's Hospital, Manchester, UK.
authors.forename: Guy
authors.initials: G
authors.lastname: Makin
authors.affiliation: Institute of Cancer Sciences, Manchester Cancer Research Centre, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.
authors.forename: Jillian
authors.initials: J
authors.lastname: Birch
authors.affiliation: Division of Epidemiology and Biostatistics, School of Medicine, University of Leeds, Leeds, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Feltbower
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Nick
authors.initials: N
authors.lastname: Bown
authors.affiliation: Paediatric Oncology and Haematology Department, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Elliott
authors.affiliation: Children and Young People's Unit, The Royal Marsden NHS Foundation Trust, Sutton, and Division of Clinical Studies and Cancer Therapeutics, The Institute of Cancer Research, Sutton, UK.
authors.forename: Lucas
authors.initials: L
authors.lastname: Moreno
authors.affiliation: Children and Young People's Unit, The Royal Marsden NHS Foundation Trust, Sutton, and Division of Clinical Studies and Cancer Therapeutics, The Institute of Cancer Research, Sutton, UK.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Barone
authors.affiliation: Children and Young People's Unit, The Royal Marsden NHS Foundation Trust, Sutton, and Division of Clinical Studies and Cancer Therapeutics, The Institute of Cancer Research, Sutton, UK.
authors.forename: Andrew Dj
authors.initials: AD
authors.lastname: Pearson
authors.affiliation: Institute of Health & Society, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Peter W
authors.initials: PW
authors.lastname: James
authors.affiliation: Newcastle Cancer Centre at the Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.|Department of Paediatric Oncology, The Great North Children's Hospital, Newcastle upon Tyne, UK.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Tweddle
authors.affiliation: Institute of Health & Society, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Richard Jq
authors.initials: RJ
authors.lastname: McNally
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000401:mortality; D009447:Neuroblastoma / Q000175:diagnosis / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D011379:Prognosis; D012008:Recurrence; D012307:Risk Factors