1. Influence of Surgical Excision on the Survival of Patients With Stage 4 High-Risk Neuroblastoma: A Report From the HR-NBL1/SIOPEN Study
- Author
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Henrik Schroeder, Ruth Ladenstein, Victoria Castel, Ana Forjaz de Lacerda, Tom Monclair, Martin J. Elliott, Sabine Irtan, Lars S. Rasmussen, Cormac Owens, Giovanni Cecchetto, Roberto Luksch, Michal Rygl, Walentyna Balwierz, Vassilios Papadakis, Peter F. Ambros, Josef Malis, Mark N. Gaze, J. Godzinski, Roly Squire, Martin L. Metzelder, Enrique Freud, Maja Beck-Popovic, Andrew D.J. Pearson, Stefano Avanzini, Jakob Stenman, Shifra Ash, Kristin Bjørnland, Sabine Sarnacki, Ulrike Pötschger, Keith Holmes, Lucas Matthyssens, Toby Trahair, Adam Bysiek, Kieran McHugh, Jean-Marc Joseph, Javier Gomez-Chacon, Ellen Ruud, Genevieve Laureys, and Dominique Valteau-Couanet
- Subjects
0301 basic medicine ,Oncology ,Male ,Cancer Research ,IMPACT ,LOCAL-CONTROL ,THERAPY ,Neuroblastoma ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,Medicine and Health Sciences ,Multicenter Studies as Topic ,High risk neuroblastoma ,Stage (cooking) ,Child ,Randomized Controlled Trials as Topic ,Cytoreduction Surgical Procedures ,CHEMOTHERAPY ,Primary tumor ,Treatment Outcome ,030220 oncology & carcinogenesis ,Child, Preschool ,Surgical excision ,Female ,medicine.medical_specialty ,RAPID COJEC ,RESECTION ,Adolescent ,MEDLINE ,EXTENSIVE SURGERY ,Disease-Free Survival ,03 medical and health sciences ,INTERNATIONAL-SOCIETY ,Internal medicine ,medicine ,Pediatric oncology ,Humans ,In patient ,Neoplasm Staging ,Proportional Hazards Models ,business.industry ,Proportional hazards model ,Infant, Newborn ,Infant ,medicine.disease ,RANDOMIZED-TRIAL ,COG A3973 ,030104 developmental biology ,business - Abstract
PURPOSE To evaluate the impact of surgeon-assessed extent of primary tumor resection on local progression and survival in patients in the International Society of Pediatric Oncology Europe Neuroblastoma Group High-Risk Neuroblastoma 1 trial. PATIENTS AND METHODS Patients recruited between 2002 and 2015 with stage 4 disease > 1 year or stage 4/4S with MYCN amplification < 1 year who had completed induction without progression, achieved response criteria for high-dose therapy (HDT), and had no resection before induction were included. Data were collected on the extent of primary tumor excision, severe operative complications, and outcome. RESULTS A total of 1,531 patients were included (median observation time, 6.1 years). Surgeon-assessed extent of resection included complete macroscopic excision (CME) in 1,172 patients (77%) and incomplete macroscopic resection (IME) in 359 (23%). Surgical mortality was 7 (0.46%) of 1,531. Severe operative complications occurred in 142 patients (9.7%), and nephrectomy was performed in 124 (8.8%). Five-year event-free survival (EFS) ± SE (0.40 ± 0.01) and overall survival (OS; 0.45 ± 0.02) were significantly higher with CME compared with IME (5-year EFS, 0.33 ± 0.03; 5-year OS, 0.37 ± 0.03; P < .001 and P = .004). The cumulative incidence of local progression (CILP) was significantly lower after CME (0.17 ± 0.01) compared with IME (0.30 ± 0.02; P < .001). With immunotherapy, outcomes were still superior with CME versus IME (5-year EFS, 0.47 ± 0.02 v 0.39 ± 0.04; P = .038); CILP was 0.14 ± 0.01 after CME and 0.27 ± 0.03 after IME ( P < .002). A hazard ratio of 1.3 for EFS associated with IME compared with CME was observed before and after the introduction of immunotherapy ( P = .030 and P = .038). CONCLUSION In patients with stage 4 high-risk neuroblastoma who have responded to induction therapy, CME of the primary tumor is associated with improved survival and local control after HDT, local radiotherapy (21 Gy), and immunotherapy.
- Published
- 2020
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