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In Reply:

Memorial Sloan-Kettering Cancer Center, New York, NY

We want to thank Dr Valteau-Couanet and the Société Française d'Oncologie Pédiatrique (SFOP) Neuroblastoma Group for their interest in the outcome of the 87 children (aged 1 to 10 years) with high-risk neuroblastoma included in our recent report on induction therapy.¹ We were encouraged by the complete/very good partial remission (CR/VGPR) rate of 80%, which was consistent over the last 15 years at Memorial Sloan-Kettering Cancer Center (MSKCC; New York, NY)—an experience that contrasted with the disappointing results among 47 similarly treated SFOP patients (aged 1 to 15 years).² The French study included patients older than those in our report; median durations between cycles were similar to those we observed. We remained cautious about Dr Valteau-Couanet's interpretation of outcome data in neuroblastoma. Estimates of event-free survival with small numbers of patients and short follow-up time (< 5 to 10 years) can be inaccurate and misleading, especially when late relapses³ and complications⁴ are not appreciated. Clearly, successful induction is necessary, but not sufficient for long-term control of high-risk metastatic neuroblastoma. Postinduction strategies—including megatherapy with stem-cell transplantation,⁵ immunotherapy,⁶ differentiation therapy,⁵ and local radiotherapy⁷ alone or in combination—will influence the final outcome. Unless postinduction treatment is similar or identical, establishing the direct impact of a particular induction on long-term survival probability is difficult, if not impossible. For example, the MSKCC protocols N6, N7, and N8 applied three different treatment strategies. They were similar in the induction chemotherapy,¹ gross total surgical resection, and hyperfractionated local radiation methods.⁷ But they differed substantially in the postinduction consolidation; protocol N6 used anti-GD2 monoclonal antibody 3F8,⁶ protocol N7 used monoclonal antibodies 3F8 and ¹³¹I-3F8,⁸ and protocol N8 incorporated megatherapy/stem-cell rescue and monoclonal antibody 3F8 plus granulocyte macrophage colony-stimulating factor.⁹ These protocols were purposely designed to keep induction therapies as near identical as possible in order to allow comparison among postinduction strategies. Keeping in mind these limitations, our patients who achieved CR/VGPR had a lower risk of relapse than those who did not, though not reaching statistical significance. Less than 5% of the children with high-risk neuroblastoma were long-term event-free survivors in the 1980s. Despite the improvement in the event-free survival rate to more than 40% in the 1990s, we continue to explore ways to improve remission induction rates¹⁰ and to measure and control minimal residual disease, which we feel is the major obstacle to cure.⁹

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Kushner BH, Kramer K, Laquaglia MP, et al: Reduction from seven to five cycles of intensive induction chemotherapy in children with high-risk neuroblastoma. J Clin Oncol 22:4888-4892, 2004[Abstract/Free Full Text]

2. Valteau-Couanet D, Michon J, Boneu A, et al: Results of induction chemotherapy in children older than 1 year with a stage 4 neuroblastoma treated with the NB 97 French Society of Pediatric Oncology (SFOP) protocol. J Clin Oncol 23:532-540, 2005[Abstract/Free Full Text]

3. Philip T, Ladenstein R, Lasset C, et al: 1070 myeloablative mega-therapy procedures followed by stem cell rescue for neuroblastoma: 17 years of European experience and conclusions—European Group for Blood and Marrow Transplant Registry Solid Tumour Working Party. Eur J Cancer 33:2130-2135, 1997

4. Laverdiere C, Cheung NK, Kushner BH, et al: Long-term complications in survivors of advanced stage neuroblastoma. Pediatr Blood Cancer 45:324-332, 2005[CrossRef][Medline]

5. Matthay KK, Villablanca JG, Seeger RC, et al: Treatment of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid: Children's Cancer Group. N Engl J Med 341:1165-1173, 1999[Abstract/Free Full Text]

6. Cheung NK, Kushner BH, Cheung IY, et al: Anti-G(D2) antibody treatment of minimal residual stage 4 neuroblastoma diagnosed at more than 1 year of age. J Clin Oncol 16:3053-3060, 1998[Abstract/Free Full Text]

7. Kushner BH, Wolden S, LaQuaglia MP, et al: Hyperfractionated low-dose radiotherapy for high-risk neuroblastoma after intensive chemotherapy and surgery. J Clin Oncol 19:2821-2828, 2001[Abstract/Free Full Text]

8. Cheung NK, Kushner BH, LaQuaglia M, et al: N7: A novel multi-modality therapy of high risk neuroblastoma (NB) in children diagnosed over 1 year of age. Med Pediatr Oncol 36:227-230, 2001[CrossRef][Medline]

9. Cheung IY, Lo Piccolo MS, Kushner BH, et al: Early molecular response of marrow disease to biologic therapy is highly prognostic in neuroblastoma. J Clin Oncol 21:3853-3858, 2003[Abstract/Free Full Text]

10. Kushner BH, Kramer K, Modak S, et al: Camptothecin analogs (irinotecan or topotecan) plus high-dose cyclophosphamide as preparative regimens for antibody-based immunotherapy in resistant neuroblastoma. Clin Cancer Res 10:84-87, 2004[Abstract/Free Full Text]

Related Correspondence

• Event-Free Survival of Patients With High-Risk Neuroblastoma Treated With an N6-Like Induction Treatment
  Dominique Valteau-Couanet
  JCO 2005 23: 6262-6263 [Full Text]

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