Significance of MYCN amplification in international neuroblastoma staging system stage 1 and 2 neuroblastoma: a report from the International Neuroblastoma Risk Group database

Abstract

Purpose: Treatment of patients with localized neuroblastoma with unfavorable biologic features is controversial. To evaluate the outcome of children with low-stage MYCN-amplified neuroblastoma and develop a rational treatment strategy, data from the International Neuroblastoma Risk Group (INRG) database were analyzed.

Patients and methods: The database is comprised of 8,800 patients. Of these, 2,660 patients (30%) had low-stage (International Neuroblastoma Staging System stages 1 and 2) neuroblastoma, known MYCN status, and available follow-up data. Eighty-seven of these patients (3%) had MYCN amplified tumors.

Results: Patients with MYCN-amplified, low-stage tumors had less favorable event-free survival (EFS) and overall survival (OS) than did patients with nonamplified tumors (53% +/- 8% and 72% +/- 7% v 90% +/- 1% and 98% +/- 1%, respectively). EFS and OS were statistically significantly higher for patients whose tumors were hyperdiploid rather than diploid (EFS, 82% +/- 20% v 37% +/- 21%; P = .0069; OS, 94% +/- 11% v 54% +/- 15%; P = .0056, respectively). No other variable had prognostic significance. Initial treatment consisted of surgery alone for 29 (33%) of 87 patients. Details of additional therapy were unknown for 14 patients. Twenty-two patients (25%) underwent surgery and moderate-intensity chemotherapy; another 22 underwent surgery, intensive chemotherapy, and radiation therapy. Nine of the latter 22 underwent stem cell transplantation. Survival in patients who received transplantation did not differ from survival in those who did not receive transplantation.

Conclusion: Among patients with low-stage, MYCN-amplified neuroblastoma, outcomes of patients with hyperdiploid tumors were statistically, significantly better than those with diploid tumors. The data suggest that tumor cell ploidy could potentially be used to identify candidates for reductions in therapy. Further study of MYCN-amplified, low-stage neuroblastoma is warranted.

Figures

Fig 1.

International Neuroblastoma Staging System stage 1 and 2 patients. (A) Event free and (B) overall survival curves for MYCN nonamplified (n = 2,573) versus amplified (n = 87) patients. The numbers of patients at risk for an event are shown along the curves at years 4 and 8.

Fig 2.

MYCN amplified International Neuroblastoma Staging System stage 1 and 2 patients (n = 87). (A) Event free and (B) overall survival curves for hyperdiploid (n = 17) versus diploid (n = 22) patients. The numbers of patients at risk for an event are shown along the curves at years 3 and 5.

Fig 3.

MYCN amplified International Neuroblastoma Staging System stage 1 and 2 patients (n = 87). (A) Event free and (B) overall survival curves for stage 1 (n = 48) versus stage 2 (n = 39) patients. The numbers of patients at risk for an event are shown along the curves at years 3 and 5.