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Evidence-Based Diagnostic Algorithm for Glioma: Analysis of the Results of Pathology Panel Review and Molecular Parameters of EORTC 26951 and 26882 Trials.
Journal article

Evidence-Based Diagnostic Algorithm for Glioma: Analysis of the Results of Pathology Panel Review and Molecular Parameters of EORTC 26951 and 26882 Trials.

  • Kros JM Johan M. Kros and Karin Huizer, Erasmus Medical Center; Pim French and Martin J. van den Bent, Dr Daniel den Hoed Cancer Center, Rotterdam, the Netherlands; Aurelio Hernández-Laín, Hospital Universitario 12 de Octubre Reseach Institute, Madrid; Teresa Ribalta, Hospital Clínic, University of Barcelona, Barcelona, Spain; Gianluca Marucci, Bellaria Hospital, University of Bologna, Bologna; Bianca Pollo, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Neurologico "C. Besta," Milano, Italy; Alex Michotte, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel; David Jaminé, Nawal Bekka, Denis Lacombe, and Thierry Gorlia, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; and Elisabeth J. Rushing, Institute for Neuropathology, University Hospital of Zurich, Zurich, Switzerland. j.m.kros@erasmusmc.nl.
  • Huizer K Johan M. Kros and Karin Huizer, Erasmus Medical Center; Pim French and Martin J. van den Bent, Dr Daniel den Hoed Cancer Center, Rotterdam, the Netherlands; Aurelio Hernández-Laín, Hospital Universitario 12 de Octubre Reseach Institute, Madrid; Teresa Ribalta, Hospital Clínic, University of Barcelona, Barcelona, Spain; Gianluca Marucci, Bellaria Hospital, University of Bologna, Bologna; Bianca Pollo, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Neurologico "C. Besta," Milano, Italy; Alex Michotte, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel; David Jaminé, Nawal Bekka, Denis Lacombe, and Thierry Gorlia, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; and Elisabeth J. Rushing, Institute for Neuropathology, University Hospital of Zurich, Zurich, Switzerland.
  • Hernández-Laín A Johan M. Kros and Karin Huizer, Erasmus Medical Center; Pim French and Martin J. van den Bent, Dr Daniel den Hoed Cancer Center, Rotterdam, the Netherlands; Aurelio Hernández-Laín, Hospital Universitario 12 de Octubre Reseach Institute, Madrid; Teresa Ribalta, Hospital Clínic, University of Barcelona, Barcelona, Spain; Gianluca Marucci, Bellaria Hospital, University of Bologna, Bologna; Bianca Pollo, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Neurologico "C. Besta," Milano, Italy; Alex Michotte, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel; David Jaminé, Nawal Bekka, Denis Lacombe, and Thierry Gorlia, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; and Elisabeth J. Rushing, Institute for Neuropathology, University Hospital of Zurich, Zurich, Switzerland.
  • Marucci G Johan M. Kros and Karin Huizer, Erasmus Medical Center; Pim French and Martin J. van den Bent, Dr Daniel den Hoed Cancer Center, Rotterdam, the Netherlands; Aurelio Hernández-Laín, Hospital Universitario 12 de Octubre Reseach Institute, Madrid; Teresa Ribalta, Hospital Clínic, University of Barcelona, Barcelona, Spain; Gianluca Marucci, Bellaria Hospital, University of Bologna, Bologna; Bianca Pollo, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Neurologico "C. Besta," Milano, Italy; Alex Michotte, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel; David Jaminé, Nawal Bekka, Denis Lacombe, and Thierry Gorlia, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; and Elisabeth J. Rushing, Institute for Neuropathology, University Hospital of Zurich, Zurich, Switzerland.
  • Michotte A Johan M. Kros and Karin Huizer, Erasmus Medical Center; Pim French and Martin J. van den Bent, Dr Daniel den Hoed Cancer Center, Rotterdam, the Netherlands; Aurelio Hernández-Laín, Hospital Universitario 12 de Octubre Reseach Institute, Madrid; Teresa Ribalta, Hospital Clínic, University of Barcelona, Barcelona, Spain; Gianluca Marucci, Bellaria Hospital, University of Bologna, Bologna; Bianca Pollo, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Neurologico "C. Besta," Milano, Italy; Alex Michotte, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel; David Jaminé, Nawal Bekka, Denis Lacombe, and Thierry Gorlia, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; and Elisabeth J. Rushing, Institute for Neuropathology, University Hospital of Zurich, Zurich, Switzerland.
  • Pollo B Johan M. Kros and Karin Huizer, Erasmus Medical Center; Pim French and Martin J. van den Bent, Dr Daniel den Hoed Cancer Center, Rotterdam, the Netherlands; Aurelio Hernández-Laín, Hospital Universitario 12 de Octubre Reseach Institute, Madrid; Teresa Ribalta, Hospital Clínic, University of Barcelona, Barcelona, Spain; Gianluca Marucci, Bellaria Hospital, University of Bologna, Bologna; Bianca Pollo, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Neurologico "C. Besta," Milano, Italy; Alex Michotte, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel; David Jaminé, Nawal Bekka, Denis Lacombe, and Thierry Gorlia, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; and Elisabeth J. Rushing, Institute for Neuropathology, University Hospital of Zurich, Zurich, Switzerland.
  • Rushing EJ Johan M. Kros and Karin Huizer, Erasmus Medical Center; Pim French and Martin J. van den Bent, Dr Daniel den Hoed Cancer Center, Rotterdam, the Netherlands; Aurelio Hernández-Laín, Hospital Universitario 12 de Octubre Reseach Institute, Madrid; Teresa Ribalta, Hospital Clínic, University of Barcelona, Barcelona, Spain; Gianluca Marucci, Bellaria Hospital, University of Bologna, Bologna; Bianca Pollo, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Neurologico "C. Besta," Milano, Italy; Alex Michotte, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel; David Jaminé, Nawal Bekka, Denis Lacombe, and Thierry Gorlia, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; and Elisabeth J. Rushing, Institute for Neuropathology, University Hospital of Zurich, Zurich, Switzerland.
  • Ribalta T Johan M. Kros and Karin Huizer, Erasmus Medical Center; Pim French and Martin J. van den Bent, Dr Daniel den Hoed Cancer Center, Rotterdam, the Netherlands; Aurelio Hernández-Laín, Hospital Universitario 12 de Octubre Reseach Institute, Madrid; Teresa Ribalta, Hospital Clínic, University of Barcelona, Barcelona, Spain; Gianluca Marucci, Bellaria Hospital, University of Bologna, Bologna; Bianca Pollo, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Neurologico "C. Besta," Milano, Italy; Alex Michotte, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel; David Jaminé, Nawal Bekka, Denis Lacombe, and Thierry Gorlia, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; and Elisabeth J. Rushing, Institute for Neuropathology, University Hospital of Zurich, Zurich, Switzerland.
  • French P Johan M. Kros and Karin Huizer, Erasmus Medical Center; Pim French and Martin J. van den Bent, Dr Daniel den Hoed Cancer Center, Rotterdam, the Netherlands; Aurelio Hernández-Laín, Hospital Universitario 12 de Octubre Reseach Institute, Madrid; Teresa Ribalta, Hospital Clínic, University of Barcelona, Barcelona, Spain; Gianluca Marucci, Bellaria Hospital, University of Bologna, Bologna; Bianca Pollo, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Neurologico "C. Besta," Milano, Italy; Alex Michotte, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel; David Jaminé, Nawal Bekka, Denis Lacombe, and Thierry Gorlia, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; and Elisabeth J. Rushing, Institute for Neuropathology, University Hospital of Zurich, Zurich, Switzerland.
  • Jaminé D Johan M. Kros and Karin Huizer, Erasmus Medical Center; Pim French and Martin J. van den Bent, Dr Daniel den Hoed Cancer Center, Rotterdam, the Netherlands; Aurelio Hernández-Laín, Hospital Universitario 12 de Octubre Reseach Institute, Madrid; Teresa Ribalta, Hospital Clínic, University of Barcelona, Barcelona, Spain; Gianluca Marucci, Bellaria Hospital, University of Bologna, Bologna; Bianca Pollo, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Neurologico "C. Besta," Milano, Italy; Alex Michotte, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel; David Jaminé, Nawal Bekka, Denis Lacombe, and Thierry Gorlia, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; and Elisabeth J. Rushing, Institute for Neuropathology, University Hospital of Zurich, Zurich, Switzerland.
  • Bekka N Johan M. Kros and Karin Huizer, Erasmus Medical Center; Pim French and Martin J. van den Bent, Dr Daniel den Hoed Cancer Center, Rotterdam, the Netherlands; Aurelio Hernández-Laín, Hospital Universitario 12 de Octubre Reseach Institute, Madrid; Teresa Ribalta, Hospital Clínic, University of Barcelona, Barcelona, Spain; Gianluca Marucci, Bellaria Hospital, University of Bologna, Bologna; Bianca Pollo, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Neurologico "C. Besta," Milano, Italy; Alex Michotte, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel; David Jaminé, Nawal Bekka, Denis Lacombe, and Thierry Gorlia, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; and Elisabeth J. Rushing, Institute for Neuropathology, University Hospital of Zurich, Zurich, Switzerland.
  • Lacombe D Johan M. Kros and Karin Huizer, Erasmus Medical Center; Pim French and Martin J. van den Bent, Dr Daniel den Hoed Cancer Center, Rotterdam, the Netherlands; Aurelio Hernández-Laín, Hospital Universitario 12 de Octubre Reseach Institute, Madrid; Teresa Ribalta, Hospital Clínic, University of Barcelona, Barcelona, Spain; Gianluca Marucci, Bellaria Hospital, University of Bologna, Bologna; Bianca Pollo, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Neurologico "C. Besta," Milano, Italy; Alex Michotte, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel; David Jaminé, Nawal Bekka, Denis Lacombe, and Thierry Gorlia, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; and Elisabeth J. Rushing, Institute for Neuropathology, University Hospital of Zurich, Zurich, Switzerland.
  • van den Bent MJ Johan M. Kros and Karin Huizer, Erasmus Medical Center; Pim French and Martin J. van den Bent, Dr Daniel den Hoed Cancer Center, Rotterdam, the Netherlands; Aurelio Hernández-Laín, Hospital Universitario 12 de Octubre Reseach Institute, Madrid; Teresa Ribalta, Hospital Clínic, University of Barcelona, Barcelona, Spain; Gianluca Marucci, Bellaria Hospital, University of Bologna, Bologna; Bianca Pollo, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Neurologico "C. Besta," Milano, Italy; Alex Michotte, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel; David Jaminé, Nawal Bekka, Denis Lacombe, and Thierry Gorlia, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; and Elisabeth J. Rushing, Institute for Neuropathology, University Hospital of Zurich, Zurich, Switzerland.
  • Gorlia T Johan M. Kros and Karin Huizer, Erasmus Medical Center; Pim French and Martin J. van den Bent, Dr Daniel den Hoed Cancer Center, Rotterdam, the Netherlands; Aurelio Hernández-Laín, Hospital Universitario 12 de Octubre Reseach Institute, Madrid; Teresa Ribalta, Hospital Clínic, University of Barcelona, Barcelona, Spain; Gianluca Marucci, Bellaria Hospital, University of Bologna, Bologna; Bianca Pollo, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Neurologico "C. Besta," Milano, Italy; Alex Michotte, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel; David Jaminé, Nawal Bekka, Denis Lacombe, and Thierry Gorlia, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; and Elisabeth J. Rushing, Institute for Neuropathology, University Hospital of Zurich, Zurich, Switzerland.
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  • 2015-04-29
Published in:
  • Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 2015
Adult
Aged
Algorithms
Biomarkers, Tumor
Brain Neoplasms
Chromosome Deletion
Chromosomes, Human, Pair 10
Chromosomes, Human, Pair 7
DNA Methylation
DNA Modification Methylases
DNA Repair Enzymes
ErbB Receptors
Evidence-Based Medicine
Female
Gene Amplification
Glioma
Humans
Isocitrate Dehydrogenase
Male
Microscopy
Middle Aged
Mutation
Proportional Hazards Models
Tumor Suppressor Proteins
User-Computer Interface
English PURPOSE
With the rapid discovery of prognostic and predictive molecular parameters for glioma, the status of histopathology in the diagnostic process should be scrutinized. Our project aimed to construct a diagnostic algorithm for gliomas based on molecular and histologic parameters with independent prognostic values.


METHODS
The pathology slides of 636 patients with gliomas who had been included in EORTC 26951 and 26882 trials were reviewed using virtual microscopy by a panel of six neuropathologists who independently scored 18 histologic features and provided an overall diagnosis. The molecular data for IDH1, 1p/19q loss, EGFR amplification, loss of chromosome 10 and chromosome arm 10q, gain of chromosome 7, and hypermethylation of the promoter of MGMT were available for some of the cases. The slides were divided in discovery (n = 426) and validation sets (n = 210). The diagnostic algorithm resulting from analysis of the discovery set was validated in the latter.


RESULTS
In 66% of cases, consensus of overall diagnosis was present. A diagnostic algorithm consisting of two molecular markers and one consensus histologic feature was created by conditional inference tree analysis. The order of prognostic significance was: 1p/19q loss, EGFR amplification, and astrocytic morphology, which resulted in the identification of four diagnostic nodes. Validation of the nodes in the validation set confirmed the prognostic value (P < .001).


CONCLUSION
We succeeded in the creation of a timely diagnostic algorithm for anaplastic glioma based on multivariable analysis of consensus histopathology and molecular parameters.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/142165
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