title: Consolidation chemoradiotherapy and autologous bone marrow transplantation versus continued chemotherapy for metastatic neuroblastoma: a report of two concurrent Children's Cancer Group studies.
abstract: OBJECTIVE
  To compare event-free survival (EFS) for patients with stage IV neuroblastoma who were treated with induction chemotherapy followed by additional courses of the same chemotherapy or by intensive chemoradiotherapy and autologous bone marrow transplantation (ABMT).
  
  
  METHODS
  Two hundred seven children who were diagnosed with stage IV neuroblastoma after 1 year of age were given five to seven courses of induction chemotherapy consisting of cisplatin, etoposide, doxorubicin, and cyclophosphamide (CCC-321-P2). This chemotherapy was continued for 13 total courses for some patients, whereas intensive chemoradiotherapy with ABMT was given to others (CCG-321-P3). The decision to continue chemotherapy versus to consolidate with chemoradiotherapy was not randomized but was made by parents and physicians. Marrow used for ABMT was purged ex vivo and was free of immunocytologically detectable neuroblastoma cells.
  
  
  RESULTS
  One hundred fifty-nine of 207 patients (77%) remained event-free during induction therapy. Of these, 67 received chemoradiotherapy/ABMT (CCG-321-P3) and 74 continued chemotherapy (CCG-321-P2). Using Cox regression analysis, the relative risk (RR) of an event after chemoradiotherapy/ABMT was estimated to be 58% of that for patients who continued chemotherapy (P = .01). Similarly, Kaplan-Meier analysis estimated EFS at four years for the chemoradiotherapy/ABMT and chemotherapy groups to be 40% and 19% respectively (P = .019). Subgroups appearing to benefit from chemoradiotherapy/ABMT were those with only a partial tumor response to induction chemotherapy (RR = 0.43; P = .008; EFS, 29% v 6%) and those whose tumors had amplification of the N-myc gene (RR = 0.26; P = .112; EFS, 67% v 0%).
  
  
  CONCLUSIONS
  Consolidation with intensive, myeloablative chemoradiotherapy followed by purged ABMT may be more effective than continuing chemotherapy for patients with stage IV neuroblastoma.
authors.affiliation: Department of Preventive Medicine, University of Southern California School of Medicine, Los Angeles, USA. dstram@nccf.org
authors.forename: D O
authors.initials: DO
authors.lastname: Stram
authors.forename: K K
authors.initials: KK
authors.lastname: Matthay
authors.forename: M
authors.initials: M
authors.lastname: O'Leary
authors.forename: C P
authors.initials: CP
authors.lastname: Reynolds
authors.forename: G M
authors.initials: GM
authors.lastname: Haase
authors.forename: J B
authors.initials: JB
authors.lastname: Atkinson
authors.forename: G M
authors.initials: GM
authors.lastname: Brodeur
authors.forename: R C
authors.initials: RC
authors.lastname: Seeger
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016465:Bone Marrow Purging; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D006801:Humans; D007223:Infant; D009447:Neuroblastoma / Q000188:drug therapy / Q000401:mortality / Q000556:secondary* / Q000628:therapy*; D012044:Regression Analysis; D015996:Survival Rate; D014182:Transplantation, Autologous