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.