Poster Presentation Advances in Neuroblastoma Research Congress 2016

Impact of age and MNA amplification (MNA) on long-term survival rates: accurate estimation and refined modeling using innovative statistical approaches.  A SIOPEN study from the high tisk neuroblastoma trial HR-NBL1/SIOPEN. (#170)

Ulrike Pötschger 1 , Peter Ambros 1 , Domonique Valteau-Couanet 2 , Martin Elliot 3 , Roberto Luksch 4 , Victoria Castel 5 , Isaac Yaniv 6 , Gudrun Schleiermacher 7 , Vassilios Parpadakis 8 , Genevieve Laureys 9 , Josef Malis 10 , Walentyna Balwierz 11 , Klaus Beiske 12 , Henrik Schroeder 13 , Ana Forjaz de Lacerda 14 , Maja Beck-Popovic 15 , Per Kogner 16 , Toby Trahair 17 , Keith Holmes 18 , MarkMark Gaze 19 , Andrew Pearson 20 , Ruth Ladenstein 1
  1. St- Anna Kinderkrebsforschung, Vienna, Austria
  2. Institut Gustav Roussy, Villejuif, France
  3. Leads Teaching Hospital NHS Trust, Leeds, United Kingdom
  4. Instituto Nazionale Tumori di Milano, Milan, Italy
  5. Hospital La Fe , Valencia, Spain
  6. Schneider's Children Medical Center, Peta Tikva, Israel
  7. Institute Curie, Paris, France
  8. Agia Sophia Children's Hospital, Athens, Greece
  9. University Hospital Gent, Gent, Belgium
  10. Petiatric Hematology/Oncology, Prague, Czech Republic
  11. Jagiellonia University Medical College, Krakow, Poland
  12. Oslo University Hospital Radiumhospitalet, Oslo, Norway
  13. University Hospital of Aarhus Skejby, Aarhus Skejby, Denmark
  14. Portuguuese Institute of Oncology, Lisboa, Portugal
  15. University Hospital, Lausanne, Switzerland
  16. Karolinska Institutet, Stockholm
  17. Kids Cancer Centre, Sydney, Australia
  18. St. George's Hospital, London, United Kingdom
  19. University College Hospital, London, United Kingdom
  20. Institute of Cancer Research, Sutton, United Kingdom


The prognostic impact of MYCN amplification (MNA) in stage 4 neuroblastoma remains unclear and the findings of large studies differ.


1005 stage 4 patients (pts) above one year of age in entered in HR-NBL1/SIOPEN treated with COJEC induction before November 2009 were evaluated. The primary endpoint was 5-year event free survival (5-yr EFS) and the pseudo-value regression model was used for statistical evaluation allowing separate investigation of short- and long-term survival probabilities without relying on proportional hazards.



The median age was 3yrs with 105pts 12-below18 months, 664pts 18mo-5yrs and 236pts above 5yrs. 591/1005pts (58%) were MNA (MNA+) and MNA was absent in 414pts (MNA-).

There is a significant interaction between age and MNA (p=0.032). The 5-yr EFS was 35% in pts 12-18 months for MNA+(n=70) and 62% for MNA- (n=35, p=0.011); in pts 18mo-5yrs. 33% in 294 MNA+ pts and 30% in 370 MNA- pts (p=0.503) and in pts> 5yrs 13% in 50 MNA+ pts and 14 % in 186 MNA- pts (p=0.933).

Metastatic CR after COJEC occurred more frequently in patients with MNA+ (46% vs 33%, p<0.001).

The 5-yr survival after relapse was 7% in MNA+ and 10% in MNA- pts. However, deaths occurred earlier in MNA+ pts: the in 1-yr post relapse survival was 25% in MNA+ and 59% in MNA- pts.


Pts below18 months without MNA have a superior long-term EFS. However, in patients with MNA, long-term EFS is similar in the younger age-groups (below18 months, 1.5-5yrs) but is significantly inferior in over 5yrs.

MNA is associated with a higher rate CR, but pts who relapse do so earlier. These differences should be considered in the design of clinical trials.