The optimal timing of surgical resection in high-risk neuroblastoma

• Published in: Journal of pediatric surgery 2016-10, Vol.51 (10), p.1665-1669
• Main Authors: Rojas, Yesenia, Jaramillo, Sergio, Lyons, Karen, Mahmood, Nadia, Wu, Meng-Fen, Liu, Hao, Vasudevan, Sanjeev A, Guillerman, R. Paul, Louis, Chrystal U, Russell, Heidi V, Nuchtern, Jed G, Kim, Eugene S
• Format: Article
• Language: English
• Subjects: Child; Child, Preschool; Disease-Free Survival; Female; Follow-Up Studies; High-risk neuroblastoma; Humans; Induction chemotherapy; Kaplan-Meier Estimate; Male; Neuroblastoma - diagnosis; Neuroblastoma - mortality; Neuroblastoma - surgery; Pediatrics; Retrospective Studies; Surgery; Surgical Procedures, Operative - methods; Surgical resection; Survival Rate - trends; Texas - epidemiology; Time Factors; Treatment Outcome
• ISSN: 0022-3468; 1531-5037
• DOI: 10.1016/j.jpedsurg.2016.05.021

Abstract 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 < 18 years 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 2 cycles of chemotherapy (12%), 20 patients received 3 cycles (40%), 13 patients received 4 cycles (26%), and 11 patients received 5 cycles (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 5 cycles of chemotherapy prior to surgery, respectively ( p = 0.07). Multivariate analysis revealed that patients who received 4 cycles of chemotherapy had a significantly lower mortality (HR: 0.11, 95% CI: 0.01–0.87, p = 0.04) compared to those with 2 cycles 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. Conclusion HRNB patients who receive 4 cycles of chemotherapy prior to surgical resection have a superior OS than patients who receive 2. Based on the superior survival of patients who received 4 cycles of chemotherapy prior to surgery, further studies are warranted to elucidate these differences.