title: [Long-term follow-ups of comprehensive therapies for stage 4 neuroblastoma].
abstract: OBJECTIVE
  To evaluate the long-term outcomes of childhood stage 4 neuroblastoma (NB) and its correlative prognostic factors.
  
  
  METHODS
  Comprehensive protocols including tumor resection, intensive chemotherapy, radiotherapy, autologous bone marrow transplantation and 13-cis-retinoid were designed and implemented. A total of 112 newly diagnosed NB stage 4 patients at Shanghai Children's Medical Center collected from June 1998 to December 2010 were treated. Their clinical features, therapeutic efficacies, long-term outcomes and prognostic factors were analyzed.
  
  
  RESULTS
  There were 69 males and 43 females with an age range of 4 months to 15 years. Among them, 12 improving patients didn't complete treatment because of parental decisions. Among those completing the comprehensive protocols, 62 cases (62.0%) achieved very good partial remission (VGPR), 20 (20.0%) achieved partial remission (PR) while another 18 (18.0%) progressed during treatment. The efficiency rate (including VGPR+PR) of treatment was 82.0 % (n = 82). The median follow-up period was 78 (56, 120) months. And 13 cases were lost after a median follow-up of 16 months. The 2, 3, 5-year event-free survival (EFS) was 56.2% (59/105) , 40.8% (40/98) and 21.1% (19/90) respectively. Age (>18 months), poor curative effect (achieving no VGPR at the end of treatment), elevated level of lactate dehydrogenase (LDH) (> 5 times normal value), bone marrow involvement and brain metastasis were poor prognostic factors (χ(2) = 12.01, 13.66, 6.29, 5.44, 16.18, all P < 0.05) . According to the multivariate estimates of hazards, age, high levels of LDH, poor curative effect and brain metastasis were associated with a worse survival (OR = 3.54, 1.89, 3.08, 3.45, all P < 0.05) . Brain metastasis predicted a worse outcome with 100% mortality rate (n = 6). Compared to traditional chemotherapy, topotecan-based chemotherapy could not improved the efficiency (52.6% (10/19) vs 63.2% (36/57) , P > 0.05) and long-term outcome (2 ys-EFS 42.1% (8/19) vs 56.4% (31/55) , P > 0.05).
  
  
  CONCLUSIONS
  The prognosis remains poor for neuroblastoma of stage 4. Age (>18 months), poor curative effect (achieving no VGPR at the end of treatment), elevated LDH level (>5 times normal value) and bone marrow infiltration are associated with worse prognosis. Brain metastasis predicts the worst with 100% death rate. Topotecan included chemotherapy can not be proved more effective in this study.
authors.affiliation: Department of Hematology/Oncology, Shanghai Children's Medical Center, Medical College of Shanghai Jiaotong University, Shanghai 200127, China.
authors.forename: Anan
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Department of Hematology/Oncology, Shanghai Children's Medical Center, Medical College of Shanghai Jiaotong University, Shanghai 200127, China.
authors.forename: Ci
authors.initials: C
authors.lastname: Pan
authors.affiliation: Department of Hematology/Oncology, Shanghai Children's Medical Center, Medical College of Shanghai Jiaotong University, Shanghai 200127, China.
authors.forename: Qidong
authors.initials: Q
authors.lastname: Ye
authors.affiliation: Department of Hematology/Oncology, Shanghai Children's Medical Center, Medical College of Shanghai Jiaotong University, Shanghai 200127, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Hematology/Oncology, Shanghai Children's Medical Center, Medical College of Shanghai Jiaotong University, Shanghai 200127, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Hematology/Oncology, Shanghai Children's Medical Center, Medical College of Shanghai Jiaotong University, Shanghai 200127, China.
authors.forename: Changying
authors.initials: C
authors.lastname: Luo
authors.affiliation: Department of Hematology/Oncology, Shanghai Children's Medical Center, Medical College of Shanghai Jiaotong University, Shanghai 200127, China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Hematology/Oncology, Shanghai Children's Medical Center, Medical College of Shanghai Jiaotong University, Shanghai 200127, China.
authors.forename: Yanjing
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Hematology/Oncology, Shanghai Children's Medical Center, Medical College of Shanghai Jiaotong University, Shanghai 200127, China.
authors.forename: Huiliang
authors.initials: H
authors.lastname: Xue
authors.affiliation: Department of Hematology/Oncology, Shanghai Children's Medical Center, Medical College of Shanghai Jiaotong University, Shanghai 200127, China.
authors.forename: Shuhong
authors.initials: S
authors.lastname: Shen
authors.affiliation: Department of Hematology/Oncology, Shanghai Children's Medical Center, Medical College of Shanghai Jiaotong University, Shanghai 200127, China. Email: yantfk@gmail.com.
authors.forename: Jingyan
authors.initials: J
authors.lastname: Tang
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000175:diagnosis / Q000628:therapy*; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome