Outcome of high-risk stage 3 neuroblastoma with myeloablative therapy and 13-cis-retinoic acid: a report from the Children's Oncology Group

Abstract

Background: The components of therapy required for patients with INSS Stage 3 neuroblastoma and high-risk features remain controversial.

Procedure: A retrospective cohort design was used to determine if intensive chemoradiotherapy with purged autologous bone marrow rescue (ABMT) and/or 13-cis-retinoic acid (13-cis-RA) improved outcome for patients with high-risk neuroblastoma that was not metastatic to distant sites. We identified 72 patients with INSS Stage 3 neuroblastoma enrolled between 1991 and 1996 on the Phase 3 CCG-3891 randomized trial. Patients were analyzed on an intent-to-treat basis using a log-rank test.

Results: The 5-year event-free survival (EFS) and overall survival (OS) rates for patients with Stage 3 neuroblastoma were 55 +/- 6% and 59 +/- 6%, respectively (n = 72). Patients randomized to ABMT (n = 20) had 5-year EFS of 65 +/- 11% and OS of 65 +/- 11% compared to 41 +/- 11 (P = 0.21) and 46 +/- 11% (P = 0.23) for patients randomized to CC (n = 23), respectively. Patients randomized to 13-cis-RA (n = 23) had 5-year EFS of 70 +/- 10% and OS of 78 +/- 9% compared to 63 +/- 12% (P = 0.67) and 67 +/- 12% (P = 0.55) for those receiving no further therapy (n = 16), respectively. Patients randomized to both ABMT and 13-cis-RA (n = 6) had a 5-year EFS of 80 +/- 11% and OS of 100%.

Conclusion: Patients with high-risk Stage 3 neuroblastoma have an overall poor prognosis despite aggressive chemoradiotherapy. Further studies are warranted to determine if myeloablative consolidation followed by 13-cis-RA maintenance therapy statistically significantly improves outcome.

Figures

Figure 1

Kaplan-Meier survival curves from time of study enrollment for patients who accepted the first randomization, by treatment group (intent-to-treat): transplantation (ABMT, n=20) versus continuation chemotherapy (CC, n=23); A) Event-free survival (p=0.2141); B) Overall survival (p=0.2279)

Figure 2

Kaplan-Meier survival curves from time of study enrollment for patients who accepted the second randomization, by treatment group (intent-to-treat): 13-cis-RA (n=23) versus no 13-cis-RA (n=16); a) Event-free survival (p=0.6684); b) Overall survival (p=0.5516)