Factors associated with recurrence and survival length following relapse in patients with neuroblastoma


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Nermine Basta1,Gail Halliday2,Guy Makin3,Jillian Birch4,Richard Feltbower5,Nick Bown6,Martin Elliott7,Lucas Moreno8,Guiseppe Barone8,Andrew Pearson8,Peter James1,Deborah Tweddle2,Richard McNally1
1Institute of Health & Society, Newcastle University,2Northern Institute for Cancer Research, Newcastle University and Department of Paediatric Oncology, The Great North Children's Hospital, Newcastle upon Tyne,3Institute of Cancer Sciences, University of Manchester & Department of Paediatric Oncology, Royal Manchester Children's Hospital,4Institute of Cancer Sciences, University of Manchester,5Division of Epidemiology and Biostatistics, University of Leeds,6Institute of Genetic Medicine, Newcastle University,7Paediatric Oncology and Haematology Department, Leeds Teaching Hospitals NHS Trust,8Children and Young People's Unit, Royal Marsden NHS Foundation Trust and Division of Clinical Studies and Cancer Therapeutics, The Institute of Cancer Research, Sutton

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.

Method

All cases of relapsed neuroblastoma, diagnosed 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

189 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 (inter quartile 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. 80% of high risk relapses occurred within 2 years of diagnosis compared with 50% of unresectable non-MNA IR disease.

Conclusion

Patients with relapsed HR neuroblastoma 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.

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