Influence of Surgical Excision on the Survival of Patients with Stage 4 High-Risk Neuroblastoma: A Report from the HR-NBL1/SIOPEN Study

Keith Holmes, Ulrike Pötschger, Andrew D.J. Pearson, Sabine Sarnacki, Giovanni Cecchetto, Javier Gomez-Chacon, Roly Squire, Enrique Freud, Adam Bysiek, Lucas E. Matthyssens, Martin Metzelder, Tom Monclair, Jakob Stenman, Michal Rygl, Lars Rasmussen, Jean Marc Joseph, Sabine Irtan, Stefano Avanzini, Jan Godzinski, Kristin BjörnlandMartin Elliott, Roberto Luksch, Victoria Castel, Shifra Ash, Walentyna Balwierz, Geneviève Laureys, Ellen Ruud, Vassilios Papadakis, Josef Malis, Cormac Owens, Henrik Schroeder, Maja Beck-Popovic, Toby Trahair, Ana Forjaz de Lacerda, Peter F. Ambros, Mark N. Gaze, Kieran McHugh, Dominique Valteau-Couanet, Ruth Lydia Ladenstein

Research output: Contribution to journalArticlepeer-review


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) 6 SE (0.40 6 0.01) and overall survival (OS; 0.45 6 0.02) were significantly higher with CME compared with IME (5-year EFS, 0.33 6 0.03; 5-year OS, 0.37 6 0.03; P, .001 and P 5 .004). The cumulative incidence of local progression (CILP) was significantly lower after CME (0.17 6 0.01) compared with IME (0.30 6 0.02; P, .001). With immunotherapy, outcomes were still superior with CME versus IME (5-year EFS, 0.47 6 0.02 v 0.39 6 0.04; P 5 .038); CILP was 0.14 6 0.01 after CME and 0.27 6 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 5 .030 and P 5 .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.

Original languageEnglish
Pages (from-to)2902-2915
Number of pages14
JournalJournal of Clinical Oncology
Issue number25
StatePublished - 2020


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