title: Prognostic significance of circulating tumor cells and bone marrow micrometastasis in advanced neuroblastoma.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Surgery, National Center for Child Health and Development, Tokyo 157-8535, Japan. kuroda-t@ncchd.go.jp
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kuroda
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Morikawa
authors.forename: Kentaro
authors.initials: K
authors.lastname: Matsuoka
authors.forename: Akihiro
authors.initials: A
authors.lastname: Fujino
authors.forename: Toshiro
authors.initials: T
authors.lastname: Honna
authors.forename: Atsuko
authors.initials: A
authors.lastname: Nakagawa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kumagai
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Masaki
authors.forename: Morihiro
authors.initials: M
authors.lastname: Saeki
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D019046:Bone Marrow Neoplasms / Q000556:secondary*; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D016259:Genes, myc; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating; D009447:Neuroblastoma / Q000097:blood / Q000235:genetics / Q000401:mortality / Q000556:secondary* / Q000628:therapy; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D014408:Biomarkers, Tumor; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; C027260:pirarubicin; D002945:Cisplatin