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

Author:

Holmes Keith1,Pötschger Ulrike2,Pearson Andrew D. J.3,Sarnacki Sabine4,Cecchetto Giovanni5,Gomez-Chacon Javier6,Squire Roly7,Freud Enrique89,Bysiek Adam10,Matthyssens Lucas E.11,Metzelder Martin12,Monclair Tom13,Stenman Jakob14,Rygl Michal15,Rasmussen Lars16,Joseph Jean-Marc17,Irtan Sabine18,Avanzini Stefano19,Godzinski Jan20,Björnland Kristin1321,Elliott Martin7,Luksch Roberto22,Castel Victoria6,Ash Shifra8,Balwierz Walentyna23,Laureys Geneviève24,Ruud Ellen1321,Papadakis Vassilios25,Malis Josef15,Owens Cormac26,Schroeder Henrik27,Beck-Popovic Maja17,Trahair Toby28,Forjaz de Lacerda Ana29,Ambros Peter F.2,Gaze Mark N.30,McHugh Kieran31,Valteau-Couanet Dominique32,Ladenstein Ruth Lydia33,

Affiliation:

1. Paediatric Surgery, St George’s Hospital London and Royal Marsden Hospital, Sutton, United Kingdom

2. Children’s Cancer Research Institute, Department of Paediatrics, Medical University of Vienna, Vienna, Austria

3. Institute of Cancer Research and Royal Marsden Hospital, Sutton, United Kingdom

4. Department of Pediatric Surgery, Necker Enfants–Malades Hospital, Assistance Publique Hôpitaux de Paris, University de Paris, Paris, France

5. Pediatric Surgery, Department of Women’s and Children’s Health, University of Padua, Padua, Italy

6. Paediatric Oncology, Paediatric Surgical Oncology Unit, Hospital Universitario La FE, Valencia, Spain

7. Paediatric Oncology, Leeds Teaching Hospital, Leeds, United Kingdom

8. Schneider Children’s Medical Center of Israel, Petach, Tikvah, Israel

9. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

10. Department of Pediatric Surgery, University Children’s Hospital, Kraków, Poland

11. Department of Gastrointestinal and Paediatric Surgery, Princess Elisabeth Children’s Hospital, Ghent University Hospital, Ghent, Belgium

12. Paediatric Surgery, Medical University of Vienna, Vienna, Austria

13. Oslo University Hospital Rikshospitalet, Oslo, Norway

14. Karolinska University Hospital, Stockholm, Sweden

15. University Hospital Motol, Prague, Czech Republic

16. Department of Surgical Gastroenterology A, Odense University Hospital, Odense, Denmark

17. University Hospital Lausanne, Lausanne, Switzerland

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

19. Pediatric Surgery Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy

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

21. University of Oslo, Oslo, Norway

22. Paediatric Oncology, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy

23. Jagiellonian University Medical College, Kraków, Poland;

24. Department of Paediatric Haematology and Oncology, Princess Elisabeth Children’s Hospital, Ghent University Hospital, Ghent, Belgium

25. Agia Sofia Children’s Hospital, Athens, Greece

26. Paediatric Haematology/Oncology, Our Lady’s Children’s Hospital, Crumlin, Dublin, Republic of Ireland

27. University Hospital of Aarhus, Aarhus, Denmark

28. Sydney Children’s Hospital, Randwick, New South Wales, Australia

29. Portuguese Institute of Oncology, Lisbon, Portugal

30. University College Hospital, London, United Kingdom

31. Paediatric Oncology, Great Ormond Street Hospital, London, United Kingdom

32. Institut Gustave Roussy, Villejuif, Paris, France

33. St Anna Children’s Hospital and Children’s Cancer Research Institute, Department of Paediatrics, Medical University of Vienna, Vienna, Austria

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.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3