Radiogenomics of neuroblastomas: Relationships between imaging phenotypes, tumor genomic profile and survival

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Abstract

Purpose

This study investigated relationships between neuroblastomas (NBs) imaging phenotypes, tumor genomic profile and patient outcome.

Patients and methods

This IRB-approved retrospective observational study included 133 NB patients (73 M, 60 F; median age 15 months, range 0–151) treated in a single institution between 1998 and 2012. A consensus review of imaging (CT-scan, MRI) categorized tumors according to both the primarily involved compartment (i.e., neck, chest, abdomen or pelvis) and the sympathetic anatomical structure the tumors rose from (i.e., cervical, paravertebral or periarterial chains, or adrenal gland). Tumor shape, volume and image-defined surgical risk factors (IDRFs) at diagnosis were recorded. Genomic profiles were assessed using array-based comparative genomic hybridization and divided into three groups: “numerical-only chromosome alterations” (NCA), “segmental chromosome alterations” (SCA) and “ MYCN amplification” (MNA). Statistical analyses included Kruskal–Wallis, Chi ² and Fisher’s exact tests and the Kaplan-Meier method with log-rank tests and Cox model for univariate and multivariate survival analyses.

Results

A significant association between the sympathetic structure origin of tumors and genomic profiles was demonstrated. NBs arising from cervical sympathetic chains were all NCA. Paravertebral NBs were NCA or SCA in 75% and 25%, respectively and none were MNA. Periarterial NBs were NCA, SCA or MNA in 33%, 56% and 11%, respectively. Adrenal NBs were NCA, SCA or MNA in 16%, 36% and 48%, respectively. Among MNA NBs, 92% originated from the adrenal gland. The sympathetic anatomical classification was significantly better correlated to overall survival than the compartmental classification (P < .0003). The tumor volume of MNA NBs was significantly higher than NCA or SCA NBs (P < .0001). Patients with initial volume less than 160 mL had significantly better overall survival (P < .009). A “single mass” pattern was significantly more frequent in NCA NBs (P = .0003). The number of IDRFs was significantly higher in MNA NBs (P < .0001).

Conclusion

Imaging phenotypes of neuroblastomas, including tumor origin along the sympathetic system, correlate with tumor genomic profile and patient outcome.

Related collections

Most cited references 35

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The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report.

Susan L. Cohn, Andrew D.J. Pearson, Wendy B. London … (2009)

Because current approaches to risk classification and treatment stratification for children with neuroblastoma (NB) vary greatly throughout the world, it is difficult to directly compare risk-based clinical trials. The International Neuroblastoma Risk Group (INRG) classification system was developed to establish a consensus approach for pretreatment risk stratification. The statistical and clinical significance of 13 potential prognostic factors were analyzed in a cohort of 8,800 children diagnosed with NB between 1990 and 2002 from North America and Australia (Children's Oncology Group), Europe (International Society of Pediatric Oncology Europe Neuroblastoma Group and German Pediatric Oncology and Hematology Group), and Japan. Survival tree regression analyses using event-free survival (EFS) as the primary end point were performed to test the prognostic significance of the 13 factors. Stage, age, histologic category, grade of tumor differentiation, the status of the MYCN oncogene, chromosome 11q status, and DNA ploidy were the most highly statistically significant and clinically relevant factors. A new staging system (INRG Staging System) based on clinical criteria and tumor imaging was developed for the INRG Classification System. The optimal age cutoff was determined to be between 15 and 19 months, and 18 months was selected for the classification system. Sixteen pretreatment groups were defined on the basis of clinical criteria and statistically significantly different EFS of the cohort stratified by the INRG criteria. Patients with 5-year EFS more than 85%, more than 75% to or = 50% to < or = 75%, or less than 50% were classified as very low risk, low risk, intermediate risk, or high risk, respectively. By defining homogenous pretreatment patient cohorts, the INRG classification system will greatly facilitate the comparison of risk-based clinical trials conducted in different regions of the world and the development of international collaborative studies.

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Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas.

Robert C. Seeger, Garrett Brodeur, Harland Sather … (1985)

Eighty-nine patients with untreated primary neuroblastomas were studied to determine the relation between the number of copies of the N-myc oncogene and survival without disease progression. Genomic amplification (3 to 300 copies) of N-myc was detected in 2 of 16 tumors in Stage II, 13 of 20 in Stage III, and 19 of 40 in Stage IV; in contrast, 8 Stage I and 5 Stage IV-S tumors all had 1 copy of the gene (P less than 0.01). Analysis of progression-free survival in all patients revealed that amplification of N-myc was associated with the worst prognosis (P less than 0.0001); the estimated progression-free survival at 18 months was 70 per cent, 30 per cent, and 5 per cent for patients whose tumors had 1, 3 to 10, or more than 10 N-myc copies, respectively. Of 16 Stage II tumors, 2 with amplification metastasized, whereas only 1 of 14 without amplification did so (P = 0.03). Stage IV tumors with amplification progressed most rapidly: nine months after diagnosis the estimated progression-free survival was 61 per cent, 47 per cent, and 0 per cent in patients whose tumors had 1, 3 to 10, or more than 10 copies, respectively (P less than 0.0001). These results suggest that genomic amplification of N-myc may have a key role in determining the aggressiveness of neuroblastomas.

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The International Neuroblastoma Risk Group (INRG) staging system: an INRG Task Force report.

Tom Monclair, Garrett Brodeur, Peter Ambros … (2009)

The International Neuroblastoma Risk Group (INRG) classification system was developed to establish a consensus approach for pretreatment risk stratification. Because the International Neuroblastoma Staging System (INSS) is a postsurgical staging system, a new clinical staging system was required for the INRG pretreatment risk classification system. To stage patients before any treatment, the INRG Task Force, consisting of neuroblastoma experts from Australia/New Zealand, China, Europe, Japan, and North America, developed a new INRG staging system (INRGSS) based on clinical criteria and image-defined risk factors (IDRFs). To investigate the impact of IDRFs on outcome, survival analyses were performed on 661 European patients with INSS stages 1, 2, or 3 disease for whom IDRFs were known. In the INGRSS, locoregional tumors are staged L1 or L2 based on the absence or presence of one or more of 20 IDRFs, respectively. Metastatic tumors are defined as stage M, except for stage MS, in which metastases are confined to the skin, liver, and/or bone marrow in children younger than 18 months of age. Within the 661-patient cohort, IDRFs were present (ie, stage L2) in 21% of patients with stage 1, 45% of patients with stage 2, and 94% of patients with stage 3 disease. Patients with INRGSS stage L2 disease had significantly lower 5-year event-free survival than those with INRGSS stage L1 disease (78% +/- 4% v 90% +/- 3%; P = .0010). Use of the new staging (INRGSS) and risk classification (INRG) of neuroblastoma will greatly facilitate the comparison of risk-based clinical trials conducted in different regions of the world.

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Author and article information

Contributors

Hervé J. Brisse:

ORCID: http://orcid.org/0000-0003-2794-5875

Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing

Thomas Blanc: Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ResourcesRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing

Gudrun Schleiermacher: Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: ResourcesRole: ValidationRole: Writing – original draftRole: Writing – review & editing

Véronique Mosseri: Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing

Pascale Philippe-Chomette: Role: ConceptualizationRole: InvestigationRole: ResourcesRole: Validation

Isabelle Janoueix-Lerosey: Role: ConceptualizationRole: MethodologyRole: ResourcesRole: SupervisionRole: ValidationRole: Writing – original draft

Gaelle Pierron: Role: ConceptualizationRole: Data curationRole: InvestigationRole: MethodologyRole: ResourcesRole: ValidationRole: Writing – original draftRole: Writing – review & editing

Eve Lapouble: Role: Data curationRole: Validation

Michel Peuchmaur: Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ResourcesRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing

Paul Fréneaux: Role: InvestigationRole: ResourcesRole: Validation

Louise Galmiche: Role: InvestigationRole: ResourcesRole: Validation

Nathalie Algret: Role: Data curationRole: InvestigationRole: MethodologyRole: Validation

Matthieu Peycelon: Role: InvestigationRole: ResourcesRole: Validation

Jean Michon: Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: ResourcesRole: SupervisionRole: Validation

Olivier Delattre: Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: SupervisionRole: Validation

Sabine Sarnacki: Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ResourcesRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing

Michael Baudis: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, CA USA )

ISSN (Electronic): 1932-6203

Publication date (Electronic): 25 September 2017

Publication date Collection: 2017

Volume: 12

Issue: 9

Electronic Location Identifier: e0185190

Affiliations

[1 ] Imaging Department, Institut Curie, Paris, France

[2 ] Paris Sciences et Lettres Research University, Paris, France

[3 ] Department of Pediatric Surgery, Necker-Enfants-Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France

[4 ] Paris-Descartes Sorbonne-Paris-Cité University, Paris, France

[5 ] Department of Pediatric Oncology, Institut Curie, Paris, France

[6 ] Unité de Génétique Somatique, Institut Curie, Paris, France

[7 ] Department of Biostatistics, Institut Curie, Paris, France

[8 ] Department of Pediatric Surgery and Urology, Robert Debré University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France

[9 ] Paris-Diderot Sorbonne-Paris-Cité University, Paris, France

[10 ] Institut Curie, INSERM, U830, Equipe Labellisée Ligue Contre le Cancer, Paris, France

[11 ] Department of Pathology, Robert Debré University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France

[12 ] Department of Biopathology, Institut Curie, Paris, France

[13 ] Department of Pathology, Necker-Enfants-Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France

Universitat Zurich, SWITZERLAND

Author notes

Competing Interests: The authors have declared that no competing interests exist.

‡ These authors also contributed equally to this work.

* E-mail: herve.brisse@ 123456curie.fr

Author information

Hervé J. Brisse http://orcid.org/0000-0003-2794-5875

Article

Publisher ID: PONE-D-17-17629

DOI: 10.1371/journal.pone.0185190

PMC ID: 5612658

PubMed ID: 28945781

SO-VID: fd0528a5-c66c-4926-b914-dee8adb58abe

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 8 May 2017

Date accepted : 5 September 2017

Page count

Figures: 4, Tables: 4, Pages: 17

Funding

Funded by: Direction Générale de l’Offre de Soins

Award ID: 4654

Award Recipient : Olivier Delattre

Funded by: Direction Générale de l’Offre de Soins

Award ID: PHRC AOM 02014 and PHRC IC2007-09

Award Recipient : Gudrun Schleiermacher

Funded by: funder-id http://dx.doi.org/10.13039/501100001677, Institut National de la Santé et de la Recherche Médicale;

Award Recipient : Olivier Delattre

Funded by: Ligue Nationale contre le Cancer

Funded by: Institut Curie

Award ID: CEST

Funded by: funder-id http://dx.doi.org/10.13039/100000047, Annenberg Foundation;

Funded by: Association des Parents et des Amis des Enfants Soignés à l’Institut Curie

Funded by: Hubert Gouin Association

Funded by: Les Bagouz à Manon

Funded by: Enfants et Santé

Funded by: Les Amis de Claire

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This study was supported by the following grants: Grant-4654 (Site de Recherche Intégré sur le Cancer, Institut National du Cancer, Direction Générale de l’Offre de Soins); http://www.e-cancer.fr/, http://social-sante.gouv.fr/ministere/organisation/directions/article/dgos-direction-generale-de-l-offre-de-soins; PHRC AOM 02014 and PHRC IC2007-09 (Direction Générale de l’Offre de Soins); http://social-sante.gouv.fr/ministere/organisation/directions/article/dgos-direction-generale-de-l-offre-de-soins; Institut National de la Santé et de la Recherche Médicale, http://www.inserm.fr/; Ligue Nationale contre le Cancer (Equipe labellisée), https://www.ligue-cancer.net/; « Carte d’Identité des Tumeurs » program (Ligue Nationale Contre le Cancer), https://www.ligue-cancer.net/; CEST of Institut Curie, https://curie.fr/. The authors also thank the following associations for their continuous support: The Annenberg foundation, https://www.annenberg.org/ The APAESIC (Association des Parents et des Amis des Enfants Soignés à l’Institut Curie), http://www.apaesic.org/; The « Association Hubert Gouin Enfance et Cancer », http://www.enfance-et-cancer.org/; « Les Bagouz à Manon », http://www.lesbagouzamanon.org/; « Enfants et Santé », http://www.enfants-cancers-sante.fr/; « Les Amis de Claire», https://curie.fr/page/association-les-amis-de-claire.

Custom metadata

Data Availability The anonymized data set necessary to replicate our study findings are at the European Genome-phenome Archive (study accession number: EGAS00001002651).

ScienceOpen disciplines: Uncategorized

Data availability: