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

被引:78
作者
Holmes, Keith [1 ,2 ]
Poetschger, Ulrike [3 ]
Pearson, Andrew D. J. [2 ,4 ]
Sarnacki, Sabine [5 ]
Cecchetto, Giovanni [6 ]
Gomez-Chacon, Javier [7 ]
Squire, Roly [8 ]
Freud, Enrique [9 ,10 ]
Bysiek, Adam [11 ]
Matthyssens, Lucas E. [12 ]
Metzelder, Martin [13 ]
Monclair, Tom [14 ]
Stenman, Jakob [15 ]
Rygl, Michal [16 ]
Rasmussen, Lars [17 ]
Joseph, Jean-Marc [18 ]
Irtan, Sabine [19 ]
Avanzini, Stefano [20 ]
Godzinski, Jan [21 ,22 ]
Bjornland, Kristin [14 ,23 ]
Elliott, Martin [8 ]
Luksch, Roberto [24 ]
Castel, Victoria [7 ]
Ash, Shifra [9 ]
Balwierz, Walentyna [25 ]
Laureys, Genevieve [26 ]
Ruud, Ellen [14 ,23 ]
Papadakis, Vassilios [27 ]
Malis, Josef [16 ]
Owens, Cormac [28 ]
Schroeder, Henrik [29 ]
Beck-Popovic, Maja [18 ]
Trahair, Toby [30 ]
de Lacerda, Ana Forjaz [31 ]
Ambros, Peter F. [3 ]
Gaze, Mark N. [32 ]
McHugh, Kieran [33 ]
Valteau-Couanet, Dominique [34 ]
Ladenstein, Ruth Lydia [3 ,35 ]
机构
[1] St Georges Hosp London, Paediat Surg, Sutton, Surrey, England
[2] Royal Marsden Hosp, Sutton, Surrey, England
[3] Med Univ Vienna, Childrens Canc Res Inst, Dept Paediat, Vienna, Austria
[4] Inst Canc Res, Sutton, Surrey, England
[5] Univ Paris, Necker Enfants Malad Hosp, AP HP, Dept Pediat Surg, Paris, France
[6] Univ Padua, Dept Womens & Childrens Hlth, Pediat Surg, Padua, Italy
[7] Hosp Univ La FE, Paediat Surg Oncol Unit, Paediat Oncol, Valencia, Spain
[8] Leeds Teaching Hosp, Paediat Oncol, Leeds, W Yorkshire, England
[9] Schneider Childrens Med Ctr Israel, Petach, Tikvah, Israel
[10] Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel
[11] Univ Childrens Hosp, Dept Pediat Surg, Krakow, Poland
[12] Ghent Univ Hosp, Princess Elisabeth Childrens Hosp, Dept Gastrointestinal & Paediat Surg, Ghent, Belgium
[13] Med Univ Vienna, Paediat Surg, Vienna, Austria
[14] Oslo Univ Hosp, Rikshosp, Oslo, Norway
[15] Karolinska Univ Hosp, Stockholm, Sweden
[16] Univ Hosp Motol, Prague, Czech Republic
[17] Odense Univ Hosp, Dept Surg Gastroenterol A, Odense, Denmark
[18] Univ Hosp Lausanne, Lausanne, Switzerland
[19] Sorbonne Univ, Armand Trousseau Hosp, AP HP, Dept Visceral & Neonatal Pediat Surg, Paris, France
[20] IRCCS Ist Giannina Gaslini, Pediat Surg Unit, Genoa, Italy
[21] Wroclaw Med Univ, Marciniak Hosp, Dept Paediat Surg, Wroclaw, Poland
[22] Wroclaw Med Univ, Dept Paediat Traumatol & Emergency Med, Wroclaw, Poland
[23] Univ Oslo, Oslo, Norway
[24] Ist Nazl Tumori, Fdn IRCCS, Paediat Oncol, Milan, Italy
[25] Jagiellonian Univ, Med Coll, Krakow, Poland
[26] Ghent Univ Hosp, Princess Elisabeth Childrens Hosp, Dept Paediat Haematol & Oncol, Ghent, Belgium
[27] Agia Sofia Childrens Hosp, Athens, Greece
[28] Our Ladys Childrens Hosp, Paediat Haematol Oncol, Dublin, Ireland
[29] Univ Hosp Aarhus, Aarhus, Denmark
[30] Sydney Childrens Hosp, Randwick, NSW, Australia
[31] Portuguese Inst Oncol, Lisbon, Portugal
[32] Univ Coll Hosp, London, England
[33] Great Ormond St Hosp Sick Children, Paediat Oncol, London, England
[34] Inst Gustave Roussy, Paris, France
[35] Med Univ Vienna, St Anna Childrens Hosp, Vienna, Austria
关键词
LOCAL-CONTROL; INTERNATIONAL-SOCIETY; EXTENSIVE SURGERY; RANDOMIZED-TRIAL; RAPID COJEC; COG A3973; IMPACT; CHEMOTHERAPY; RESECTION; THERAPY;
D O I
10.1200/JCO.19.03117
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 withMYCNamplification < 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 andP= .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 +/- 0.02v0.39 +/- 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 andP= .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.
引用
收藏
页码:2902 / +
页数:15
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