Prognostic significance of circulating tumor cells and bone marrow micrometastasis in advanced neuroblastoma

J Pediatr Surg. 2008 Dec;43(12):2182-5. doi: 10.1016/j.jpedsurg.2008.08.046.

Abstract

Purpose: The aim of this study was to study the prognostic significance of circulating tumor cells (CTC) and the appropriate indications for aggressive surgery in advanced neuroblastoma.

Materials and methods: Micrometastasis was sequentially explored using our reverse transcriptase-polymerase chain reaction method in 29 neuroblastoma patients (International Neuroblastoma Staging System stage 4, n = 24; stage 3, n = 5) who treated at our department with the united chemotherapeutic regimen since 1991. Their medical records and detection of CTC and/or the bone marrow micrometastasis were retrospectively reviewed then analyzed statistically.

Results: The overall survival rate was 58.6% (17/29). Circulating tumor cells were detected in 55.6% of the stage 4 patients, and all deaths were related to systemic metastases in the CTC-positive patients. The detection of CTC scarcely associated with MYCN amplification. In the patients showing MYCN amplification but no CTC, all deaths were related to local relapse or chemotherapy-associated complications. The survival rate was not significantly different between the patients with and without MYCN amplification (56.8% vs 52.7%). However, it was significantly lower in the patients with CTC and/or persistent bone marrow micrometastasis compared to those without detectable micrometastasis (33.8% vs 87.5%; P < .05).

Conclusions: The presence of CTC and/or persistent micrometastasis may indicate a significantly high risk, regardless of MYCN amplification. Patients with MYCN amplification but no micrometastasis would be most benefited by highly intensive surgery.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor
  • Bone Marrow Neoplasms / secondary*
  • Child, Preschool
  • Cisplatin / administration & dosage
  • Combined Modality Therapy
  • Cyclophosphamide / administration & dosage
  • Doxorubicin / administration & dosage
  • Doxorubicin / analogs & derivatives
  • Etoposide / administration & dosage
  • Female
  • Genes, myc
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Infant
  • Kaplan-Meier Estimate
  • Male
  • Neoplasm Staging
  • Neoplastic Cells, Circulating*
  • Neuroblastoma / blood
  • Neuroblastoma / genetics
  • Neuroblastoma / mortality
  • Neuroblastoma / secondary*
  • Neuroblastoma / therapy
  • Prognosis
  • Radiotherapy, Adjuvant
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vincristine / administration & dosage

Substances

  • Biomarkers, Tumor
  • Vincristine
  • Etoposide
  • Doxorubicin
  • Cyclophosphamide
  • pirarubicin
  • Cisplatin