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

International Society of Paediatric Oncology Europe Neuroblastoma Group (SIOPEN)

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)2902-2915
Number of pages14
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology
Volume38
Issue number25
DOIs
Publication statusPublished - Sep 1 2020

Keywords

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols/therapeutic use
  • Child
  • Child, Preschool
  • Cytoreduction Surgical Procedures/adverse effects
  • Disease-Free Survival
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Multicenter Studies as Topic
  • Neoplasm Staging
  • Neuroblastoma/mortality
  • Proportional Hazards Models
  • Randomized Controlled Trials as Topic
  • Treatment Outcome

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