Age Dependency of the Prognostic Impact of Tumor Genomics in Localized Resectable MYCN-Nonamplified Neuroblastomas. Report From the SIOPEN Biology Group on the LNESG Trials and a COG Validation Group

被引：15

作者：

Ambros, Inge M. ^{[1
]}

Tonini, Gian-Paolo ^{[2
]}

Poetschger, Ulrike ^{[1
]}

Gross, Nicole ^{[3
]}

Mosseri, Veronique ^{[4
]}

Beiske, Klaus ^{[5
]}

Berbegall, Ana P. ^{[6
,7
]}

Benard, Jean ^{[8
]}

Bown, Nick ^{[9
]}

Caron, Huib ^{[10
]}

Combaret, Valerie ^{[11
]}

Couturier, Jerome ^{[12
]}

Defferrari, Raffaella ^{[13
]}

Delattre, Olivier ^{[14
]}

Jeison, Marta ^{[15
]}

Kogner, Per ^{[16
]}

Lunec, John ^{[17
]}

Marques, Barbara ^{[18
]}

Martinsson, Tommy ^{[19
]}

Mazzocco, Katia ^{[13
]}

Noguera, Rosa ^{[6
,7
]}

Schleiermacher, Gudrun ^{[14
,20
]}

Valent, Alexander ^{[8
]}

Van Roy, Nadine ^{[21
]}

Villamon, Eva ^{[6
,7
]}

Janousek, Dasa ^{[1
]}

Pribill, Ingrid ^{[1
]}

Glogova, Evgenia ^{[1
]}

Attiyeh, Edward F. ^{[22
]}

Hogarty, Michael D. ^{[22
]}

Monclair, Tom F. ^{[23
]}

Holmes, Keith ^{[24
]}

Valteau-Couanet, Dominique ^{[25
]}

Castel, Victoria ^{[26
]}

Tweddle, Deborah A. ^{[27
]}

Park, Julie R. ^{[28
,29
]}

Cohn, Sue ^{[30
]}

Ladenstein, Ruth ^{[1
,31
]}

Beck-Popovic, Maja ^{[32
]}

De Bernardi, Bruno ^{[33
]}

Michon, Jean ^{[20
]}

Pearson, Andrew D. J. ^{[34
]}

Ambros, Peter F. ^{[1
,31
]}

机构：

[1] St Anna Kinderkrebsforsch, Childrens Canc Res Inst, Zimmermannpl 10, A-1090 Vienna, Austria

[2] Fdn Citta Speranza, Paediat Res Inst, Neuroblastoma Lab, Padua, Italy

[3] Univ Hosp, Dept Pediat, Pediat Oncol Res, Lausanne, Switzerland

[4] Inst Curie, Serv Biostat, Paris, France

[5] Oslo Univ Hosp, Dept Pathol, Rikshosp, Oslo, Norway

[6] Univ Valencia, Med Sch, Dept Pathol, Fdn Investigac Hosp Clin Univ Valencia, Valencia, Spain

[7] Ctr Investigac Biomed Red Canc, Madrid, Spain

[8] Inst Gustave Roussy, Serv Pathol Mol, Dept Biol & Pathol Med, Villejuif, France

[9] Northern Genet Serv, Newcastle Upon Tyne, Tyne & Wear, England

[10] Acad Med Ctr, Emma Childrens Hosp, Dept Pediat Oncol, Amsterdam, Netherlands

[11] Ctr Leon Berard, Lab Rech Translat, Lyon, France

[12] Inst Curie, Unit Genet Somat & Cytogenet, Paris, France

[13] Ist Giannina Gaslini, Dept Pathol, Genoa, Italy

[14] INSERM, U830, Lab Genet & Biol Canc, Paris, France

[15] Schneider Childrens Med Ctr Israel, Pediat Hematol Oncol Dept, Ca Cytogenet Lab, Petah Tiqwa, Israel

[16] Karolinska Inst, Astrid Lindgren Childrens Hosp, Childhood Canc Res Unit, Stockholm, Sweden

[17] Newcastle Univ, Biosci Inst, Newcastle Upon Tyne, Tyne & Wear, England

[18] Inst Nacl Saude Doutor Ricardo Jorge, Ctr Genet Humana, Lisbon, Portugal

[19] Univ Gothenburg, Sahlgrenska Univ Hosp, Inst Biomed, Dept Clin Genet, Gothenburg, Sweden

[20] Inst Curie, Dept Pediat, Paris, France

[21] Ghent Univ Hosp, Ctr Med Genet, Ghent, Belgium

[22] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA

[23] Univ Hosp, Div Surg, Rikshosp, Sect Paediat Surg, Oslo, Norway

[24] St George Hosp, Dept Paediat Surg, London, England

[25] Gustave Roussy, Dept Cancerol Enfant & Adolescent, Villejuif, France

[26] Hosp Univ La Fe, Unidad Oncol Pediat, Valencia, Spain

[27] Newcastle Univ, Wolfson Childhood Canc Res Ctr, Translat & Clin Res Inst, Newcastle Upon Tyne, Tyne & Wear, England

[28] Seattle Childrens Hosp, Seattle, WA USA

[29] Univ Washington, Sch Med, Seattle, WA USA

[30] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA

[31] Med Univ Vienna, Dept Pediat, Vienna, Austria

[32] Univ Hosp Lausanne, Pediat Hematol Oncol Unit, Lausanne, Switzerland

[33] Giannina Gaslini Childrens Hosp, Dept Paediat Haematol & Oncol, Genoa, Italy

[34] Royal Marsden Hosp, Inst Canc Res, Sutton, Surrey, England

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2020年 / 38卷 / 31期

关键词：

SEGMENTAL CHROMOSOMAL ALTERATIONS; EUROPEAN-INTERNATIONAL-SOCIETY; STAGE; 4; NEUROBLASTOMA; RISK GROUP; PATHOLOGY CLASSIFICATION; SPONTANEOUS REGRESSION; PRIMARY THERAPY; SCHWANN-CELLS; ARM; 17Q; N-MYC;

D O I：

10.1200/JCO.18.02132

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PURPOSEFor localized, resectable neuroblastoma without MYCN amplification, surgery only is recommended even if incomplete. However, it is not known whether the genomic background of these tumors may influence outcome.PATIENTS AND METHODSDiagnostic samples were obtained from 317 tumors, International Neuroblastoma Staging System stages 1/2A/2B, from 3 cohorts: Localized Neuroblastoma European Study Group I/II and Children's Oncology Group. Genomic data were analyzed using multi- and pangenomic techniques and fluorescence in-situ hybridization in 2 age groups (cutoff age, 18 months) and were quality controlled by the International Society of Pediatric Oncology European Neuroblastoma (SIOPEN) Biology Group.RESULTSPatients with stage 1 tumors had an excellent outcome (5-year event-free survival [EFS] standard deviation [SD], 95% +/- 2%; 5-year overall survival [OS], 99% +/- 1%). In contrast, patients with stage 2 tumors had a reduced EFS in both age groups (5-year EFS +/- SD, 84% +/- 3% in patients < 18 months of age and 75% <plus/minus> 7% in patients >= 18 months of age). However, OS was significantly decreased only in the latter group (5-year OS +/- SD in < 18months and <greater than or equal to> 18months, 96% +/- 2% and 81% +/- 7%, respectively; P = .001). In < 18months, relapses occurred independent of segmental chromosome aberrations (SCAs); only 1p loss decreased EFS (5-year EFS <plus/minus> SD in patients 1p loss and no 1p loss, 62% +/- 13% and 87% +/- 3%, respectively; P = .019) but not OS (5-year OS +/- SD, 92% +/- 8% and 97% +/- 2%, respectively). In patients >= 18 months, only SCAs led to relapse and death, with 11q loss as the strongest marker (11q loss and no 11q loss: 5-year EFS +/- SD, 48% +/- 16% and 85% +/- 7%, P = .033; 5-year OS +/- SD, 46% +/- 22% and 92% +/- 6%, P = .038).CONCLUSIONGenomic aberrations of resectable non-MYCN-amplified stage 2 neuroblastomas have a distinct age-dependent prognostic impact. Chromosome 1p loss is a risk factor for relapse but not for diminished OS in patients < 18 months, SCAs (especially 11q loss) are risk factors for reduced EFS and OS in those > 18months. In older patients with SCA, a randomized trial of postoperative chemotherapy compared with observation alone may be indicated.

引用

页码：3685 / +

页数：15

共 59 条

[1] A mechanistic classification of clinical phenotypes in neuroblastoma [J].

Ackermann, Sandra ;

Cartolano, Maria ;

Hero, Barbara ;

Welte, Anne ;

Kahlert, Yvonne ;

Roderwieser, Andrea ;

Bartenhagen, Christoph ;

Walter, Esther ;

Gecht, Judith ;

Kerschke, Laura ;

Volland, Ruth ;

Menon, Roopika ;

Heuckmann, Johannes M. ;

Gartlgruber, Moritz ;

Hartlieb, Sabine ;

Henrich, Kai-Oliver ;

Okonechnikov, Konstantin ;

Altmueller, Janine ;

Nuernberg, Peter ;

Lefever, Steve ;

de Wilde, Bram ;

Sand, Frederik ;

Ikram, Fakhera ;

Rosswog, Carolina ;

Fischer, Janina ;

Theissen, Jessica ;

Hertwig, Falk ;

Singhi, Aatur D. ;

Simon, Thorsten ;

Vogel, Wenzel ;

Perner, Sven ;

Krug, Barbara ;

Schmidt, Matthias ;

Rahmann, Sven ;

Achter, Viktor ;

Lang, Ulrich ;

Vokuhl, Christian ;

Ortmann, Monika ;

Buettner, Reinhard ;

Eggert, Angelika ;

Speleman, Frank ;

O'Sullivan, Roderick J. ;

Thomas, Roman K. ;

Berthold, Frank ;

Vandesompele, Jo ;

Schramm, Alexander ;

Westermann, Frank ;

Schulte, Johannes H. ;

Peifer, Martin ;

Fischer, Matthias .

SCIENCE, 2018, 362 (6419) :1165-+

[2] Role of ploidy, chromosome 1p, and Schwann cells in the maturation of neuroblastoma [J].

Ambros, IM ;

Zellner, A ;

Roald, B ;

Amann, G ;

Ladenstein, R ;

Printz, D ;

Gadner, H ;

Ambros, PF .

NEW ENGLAND JOURNAL OF MEDICINE, 1996, 334 (23) :1505-1511

[3] Quality assessment of genetic markers used for therapy stratification [J].

Ambros, IM ;

Benard, J ;

Boavida, M ;

Bown, N ;

Caron, H ;

Combaret, V ;

Couturier, J ;

Darnfors, C ;

Delattre, O ;

Freeman-Edward, J ;

Gambini, C ;

Gross, N ;

Hattinger, CM ;

Luegmayr, A ;

Lunec, J ;

Martinsson, T ;

Mazzocco, K ;

Navarro, S ;

Noguera, R ;

O'Neill, S ;

Pötschger, U ;

Rumpler, S ;

Speleman, F ;

Tonini, GP ;

Valent, A ;

Van Roy, N ;

Amann, G ;

De Bernardi, B ;

Kogner, P ;

Ladenstein, R ;

Mickon, J ;

Pearson, ADJ ;

Ambros, PF .

JOURNAL OF CLINICAL ONCOLOGY, 2003, 21 (11) :2077-2084

[4]

Ambros IM, 2001, MED PEDIATR ONCOL, V36, P163

[5] SCHWANN-CELLS IN NEUROBLASTOMA [J].

AMBROS, IM ;

AMBROS, PF .

EUROPEAN JOURNAL OF CANCER, 1995, 31A (04) :429-434

[6] International consensus for neuroblastoma molecular diagnostics: report from the International Neuroblastoma Risk Group (INRG) Biology Committee [J].

Ambros, P. F. ;

Ambros, I. M. ;

Brodeur, G. M. ;

Haber, M. ;

Khan, J. ;

Nakagawara, A. ;

Schleiermacher, G. ;

Speleman, F. ;

Spitz, R. ;

London, W. B. ;

Cohn, S. L. ;

Pearson, A. D. J. ;

Maris, J. M. .

BRITISH JOURNAL OF CANCER, 2009, 100 (09) :1471-1482

[7] REGRESSION AND PROGRESSION IN NEUROBLASTOMA - DOES GENETICS PREDICT TUMOR BEHAVIOR [J].

AMBROS, PF ;

AMBROS, IM ;

STREHL, S ;

BAUER, S ;

LUEGMAYR, A ;

KOVAR, H ;

LADENSTEIN, R ;

FINK, FM ;

HORCHER, E ;

PRINTZ, G ;

MUTZ, I ;

SCHILLING, F ;

URBAN, C ;

GADNER, H .

EUROPEAN JOURNAL OF CANCER, 1995, 31A (04) :510-515

[8] Chromosome 1p and 11q deletions and outcome in neuroblastoma [J].

Attiyeh, EF ;

London, WB ;

Mossé, YP ;

Wang, Q ;

Winter, C ;

Khazi, D ;

McGrady, PW ;

Seeger, RC ;

Look, AT ;

Shimada, H ;

Brodeur, GM ;

Cohn, SL ;

Matthay, KK ;

Maris, JM .

NEW ENGLAND JOURNAL OF MEDICINE, 2005, 353 (21) :2243-2253

[9] The genetic tumor background is an important determinant for heterogeneous MYCN-amplified neuroblastoma [J].

Bogen, Dominik ;

Brunner, Clemens ;

Walder, Diana ;

Ziegler, Andrea ;

Abbasi, Reza ;

Ladenstein, Ruth L. ;

Noguera, Rosa ;

Martinsson, Tommy ;

Amann, Gabriele ;

Schilling, Freimut H. ;

Ussowicz, Marek ;

Benesch, Martin ;

Ambros, Peter F. ;

Ambros, Inge M. .

INTERNATIONAL JOURNAL OF CANCER, 2016, 139 (01) :153-163

[10] Gain of chromosome arm 17q and adverse outcome in patients with neuroblastoma [J].

Bown, N ;

Cotterill, S ;

Lastowska, M ;

O'Neill, S ;

Pearson, ADJ ;

Plantaz, D ;

Meddeb, M ;

Danglot, G ;

Brinkschmidt, C ;

Christiansen, H ;

Laureys, G ;

Speleman, F .

NEW ENGLAND JOURNAL OF MEDICINE, 1999, 340 (25) :1954-1961

← 1 2 3 4 5 6 →