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Results of induction chemotherapy in children older than 18 months with stage-4 neuroblastoma treated with an adaptive-to-response modified N7 protocol (mN7)

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Abstract

Purpose

We report the response rate in children older than 18 months with stage 4 Neuroblastoma, using a modified dose-intensive, response-adaptive, induction mN7 protocol.

Methods

From 2005 to 2012, 24 patients were treated with the mN7 protocol. Phase 1 included five MSKCC N7 cycles and surgery and two high-dose cyclophosphamide-topotecan (HD-CT) cycles for those who did not achieve complete remission (CR) and negative bone marrow (BM) minimal residual disease (MRD) status (CR+MRD-). Phase 2 consisted of myeloablative doses of topotecan, thiotepa and carboplatin plus hyperfractionated RT. Phase 3 included isotretinoin and 3F8 immunotherapy plus GM-CSF. BM MRD was monitored using GD2 synthase, PHOX2B and cyclin D1 mRNAs.

Results

After 3 cycles, all patients showed BM complete histological clearance and 6 (25 %) were MRD-. Twenty of 21 s-look surgeries achieved macroscopic complete resection. After 5 cycles and surgery, 123I-MIBG scan was negative in 15 (62.5 %) cases, BM disease by histology was negative in 23 (96 %) and 10 (42 %) patients were MRD-. Twelve (50 %) pts were in CR, 2 in very good partial response (VGPR), 9 partial response (PR) and one had progressive disease. With 2 HD-CT extra cycles, 17 (71 %) pts achieved CR+MRD- status moving to phase 2. Overall and event-free survival at 3 years for the 17 patients who achieved CR+MRD- is 65 and 53 %, respectively, median follow-up 47 months. Seven (29 %) patients never achieved CR+MRD-. Univariate Cox regression analysis shows CR+MRD- status after mN7 induction as the only statistically significant prognostic factor to predict overall survival.

Conclusions

mN7 induction regimen produced a CR+MRD- rate of 71 %. CR+MRD- status following induction was the only predictive marker of long-term survival.

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Acknowledgments

This is an original article and has not been previously presented or submitted for publication. Generous donations from Alicia Pueyo and NEN (Asociación de padres de Niños Enfermos de Neuroblastoma) Foundations.

Conflict of interest

The authors have no conflict of interests.

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Authors and Affiliations

  1. Department of Oncology, Hospital Sant Joan de Déu, Barcelona, Passeig Sant Joan de Déu, 2, Esplugues de Llobregat, 08950, Barcelona, Spain

    J. Mora, O. Cruz, C. Lavarino, A. Parareda, H. Salvador & C. de Torres

  2. Laboratory of Biostatistics and Epidemiology, Universitat Autònoma, Barcelona, Spain

    J. Rios

  3. Department of Surgery, Hospital Sant Joan de Déu, Barcelona, Barcelona, Spain

    M. Vancells & R. Carrasco

  4. Department of Pathology, Hospital Sant Joan de Déu, Barcelona, Barcelona, Spain

    M. Suñol

  5. Department of Neurosurgery, Hospital Sant Joan de Déu, Barcelona, Barcelona, Spain

    A. Guillen

  6. Clinical Pharmacology Service, IDIBAPS, Hospital Clínic, Barcelona, Spain

    J. Rios

  7. CETIR Institute of Nuclear Medicine, Barcelona, Spain

    S. Mañé

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  1. J. Mora
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Correspondence to J. Mora.

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Mora, J., Cruz, O., Lavarino, C. et al. Results of induction chemotherapy in children older than 18 months with stage-4 neuroblastoma treated with an adaptive-to-response modified N7 protocol (mN7). Clin Transl Oncol 17, 521–529 (2015). https://doi.org/10.1007/s12094-014-1273-8

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  • DOI: https://doi.org/10.1007/s12094-014-1273-8

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