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.

Agia Sofia Children's Hospital Athens Greece

Children's Cancer Research Institute Department of Paediatrics Medical University of Vienna Vienna Austria

Department of Gastrointestinal and Paediatric Surgery Princess Elisabeth Children's Hospital Ghent University Hospital Ghent Belgium

Department of Paediatric Haematology and Oncology Princess Elisabeth Children's Hospital Ghent University Hospital Ghent Belgium

Department of Paediatric Surgery Marciniak Hospital and Department of Paediatric Traumatology and Emergency Medicine Wroclaw Medical University Wroclaw Poland

Department of Pediatric Surgery Necker Enfants Malades Hospital Assistance Publique Hôpitaux de Paris University de Paris Paris France

Department of Pediatric Surgery University Children's Hospital Kraków Poland

Department of Surgical Gastroenterology A Odense University Hospital Odense Denmark

Institut Gustave Roussy Villejuif Paris France

Institute of Cancer Research and Royal Marsden Hospital Sutton United Kingdom

Jagiellonian University Medical College Kraków Poland

Karolinska University Hospital Stockholm Sweden

Oslo University Hospital Rikshospitalet Oslo Norway

Paediatric Haematology Oncology Our Lady's Children's Hospital Crumlin Dublin Republic of Ireland

Paediatric Oncology Fondazione IRCCS Istituto Nazionale dei Tumori Milan Italy

Paediatric Oncology Great Ormond Street Hospital London United Kingdom

Paediatric Oncology Leeds Teaching Hospital Leeds United Kingdom

Paediatric Oncology Paediatric Surgical Oncology Unit Hospital Universitario La FE Valencia Spain

Paediatric Surgery Medical University of Vienna Vienna Austria

Paediatric Surgery St George's Hospital London and Royal Marsden Hospital Sutton United Kingdom

Pediatric Surgery Department of Women's and Children's Health University of Padua Padua Italy

Pediatric Surgery Unit IRCCS Istituto Giannina Gaslini Genoa Italy

Portuguese Institute of Oncology Lisbon Portugal

Sackler School of Medicine Tel Aviv University Tel Aviv Israel

Schneider Children's Medical Center of Israel Petach Tikvah Israel

Sorbonne University Department of Visceral and Neonatal Pediatric Surgery Armand Trousseau Hospital Assistance Publique Hôpitaux de Paris Paris France

St Anna Children's Hospital and Children's Cancer Research Institute Department of Paediatrics Medical University of Vienna Vienna Austria

Sydney Children's Hospital Randwick New South Wales Australia

University College Hospital London United Kingdom

University Hospital Lausanne Lausanne Switzerland

University Hospital Motol Prague Czech Republic

University Hospital of Aarhus Aarhus Denmark

University of Oslo Oslo Norway

Citace poskytuje Crossref.org

Frequency and Prognostic Impact of ALK Amplifications and Mutations in the European Neuroblastoma Study Group (SIOPEN) High-Risk Neuroblastoma Trial (HR-NBL1)

Zobrazit více v PubMed

ClinicalTrials.gov
NCT01704716

EudraCT
2006-001489-17