The optimal timing of surgical resection in high-risk neuroblastoma.
BACKGROUND
While most high-risk neuroblastoma (HRNB) patients are enrolled in cooperative group or institutional protocols, variability exists within these protocols as to when surgical resection of the primary tumor should be performed after neoadjuvant induction chemotherapy. We sought to determine if the number of chemotherapy cycles prior to surgery affects surgical or survival outcomes in HRNB patients.


METHODS
We performed a retrospective review of all HRNB patients <18years of age from 2000 to 2010, at Texas Children's Hospital. Patients were stratified based on the number of neoadjuvant induction chemotherapy cycles prior to surgical resection. Pre and post- chemotherapy tumor size, MYCN status, iodine-131-metaiodobenzylguanidine (MIBG) score at diagnosis, extent of surgical resection, estimated surgical blood loss, post-operative outcomes, and event free (EFS) and overall survival (OS) were evaluated. Data were analyzed using Wilcoxon rank-sum test, Kruskal-Wallis test, Fisher's exact test, Kaplan-Meier analyses, and Cox regression analyses. P-value <0.05 was considered significant.


RESULTS
Data from 50 patients with HRNB were analyzed. Patients were stratified by the number of cycles of chemotherapy received prior to surgery. Six patients received 2cycles of chemotherapy (12%), 20 patients received 3cycles (40%), 13 patients received 4cycles (26%), and 11 patients received 5cycles (22%) prior to surgical resection of the primary tumor. The 5-year OS was 33%, 45%, 83% and 36% in patients who received 2, 3, 4 and 5cycles of chemotherapy prior to surgery, respectively (p=0.07). Multivariate analysis revealed that patients who received 4cycles of chemotherapy had a significantly lower mortality (HR: 0.11, 95% CI: 0.01-0.87, p=0.04) compared to those with 2cycles of chemotherapy. Among the different cohorts, there were no differences with respect to MYCN status, MIBG score at diagnosis, incidence of bone marrow metastasis, extent of surgical resection, estimated blood loss, incidence of post-operative complications, or length of stay.


CONCLUSIONS
HRNB patients who receive 4cycles of chemotherapy prior to surgical resection have a superior OS than patients who receive 2. Based on the superior survival of patients who received 4cycles of chemotherapy prior to surgery, further studies are warranted to elucidate these differences.
Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Texas Children's Hospital, Baylor College of Medicine, Houston, TX.
Yesenia
Y
Rojas
Department of Radiation Oncology, Baylor College of Medicine, Houston, TX.
Sergio
S
Jaramillo
Department of Radiology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX.
Karen
K
Lyons
Department of Radiology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX.
Nadia
N
Mahmood
Division of Biostatistics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX.
Meng-Fen
MF
Wu
Division of Biostatistics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX.
Hao
H
Liu
Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Texas Children's Hospital, Baylor College of Medicine, Houston, TX.
Sanjeev A
SA
Vasudevan
Department of Radiology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX.
R Paul
RP
Guillerman
Section of Hematology-Oncology, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, TX.
Chrystal U
CU
Louis
Section of Hematology-Oncology, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, TX.
Heidi V
HV
Russell
Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Texas Children's Hospital, Baylor College of Medicine, Houston, TX.
Jed G
JG
Nuchtern
Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Texas Children's Hospital, Baylor College of Medicine, Houston, TX; Division of Pediatric Surgery, Department of Surgery, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA. Electronic address: eugeneskim@chla.usc.edu.
Eugene S
ES
Kim
D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D009447:Neuroblastoma / Q000175:diagnosis / Q000401:mortality / Q000601:surgery*; D012189:Retrospective Studies; D013514:Surgical Procedures, Operative / Q000379:methods*; D015996:Survival Rate / Q000639:trends; D013781:Texas / Q000453:epidemiology; D013997:Time Factors; D016896:Treatment Outcome
High-risk neuroblastoma; Induction chemotherapy; Surgical resection