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Semantic imaging features predict disease progression and survival in glioblastoma multiforme patients

Semantische Bildeigenschaften prognostizieren Tumorprogression und Überleben von Patienten mit Glioblastoma multiforme

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Abstract

Background

For glioblastoma (GBM), multiple prognostic factors have been identified. Semantic imaging features were shown to be predictive for survival prediction. No similar data have been generated for the prediction of progression. The aim of this study was to assess the predictive value of the semantic visually accessable REMBRANDT [repository for molecular brain neoplasia data] images (VASARI) imaging feature set for progression and survival, and the creation of joint prognostic models in combination with clinical and pathological information.

Methods

189 patients were retrospectively analyzed. Age, Karnofsky performance status, gender, and MGMT promoter methylation and IDH mutation status were assessed. VASARI features were determined on pre- and postoperative MRIs. Predictive potential was assessed with univariate analyses and Kaplan–Meier survival curves. Following variable selection and resampling, multivariate Cox regression models were created. Predictive performance was tested on patient test sets and compared between groups. The frequency of selection for single variables and variable pairs was determined.

Results

For progression free survival (PFS) and overall survival (OS), univariate significant associations were shown for 9 and 10 VASARI features, respectively. Multivariate models yielded concordance indices significantly different from random for the clinical, imaging, combined, and combined + MGMT models of 0.657, 0.636, 0.694, and 0.716 for OS, and 0.602, 0.604, 0.633, and 0.643 for PFS. “Multilocality,” “deep white-matter invasion,” “satellites,” and “ependymal invasion” were over proportionally selected for multivariate model generation, underlining their importance.

Conclusions

We demonstrated a predictive value of several qualitative imaging features for progression and survival. The performance of prognostic models was increased by combining clinical, pathological, and imaging features.

Zusammenfassung

Einleitung

Für das Glioblastoma multiforme wurden bereits multiple prognostische Faktoren identifiziert. Semantische Bildeigenschaften zeigten eine prognostische Aussagekraft für das Überleben. Die Wertigkeit zur Vorhersage der Krankheitsprogression bleibt unklar. Ziele der Studie waren die prognostische Wertigkeit der sog. VASARI-Bildeigenschaften für Krankheitsprogression und Überleben zu evaluieren und kombinierte Vorhersagemodelle unter Beachtung klinischer und pathologischer Informationen zu generieren.

Methoden

Von 189 Patienten wurden retrospektiv Alter, Karnofsky-Index, Geschlecht, MGMT-Promotor-Methylierung und IDH-Mutationsstatus erfasst. “Visually Accessable REMBRANDT [Repository for Molecular Brain Neoplasia Data] Images”(VASARI)-Eigenschaften wurden in prä- und postoperativen MRT-Studien bestimmt. Die Vorhersagekraft einzelner Eigenschaften wurde univariat und anhand von Kaplan-Meyer-Kurven analysiert. Nach Variablenselektion und Resampling wurden multivariate Cox-Regressionsmodelle generiert. Die prädiktive Vorhersagekraft der Modelle wurde mit Testpatienten ermittelt und die Modelle wurden miteinander verglichen. Die Selektionsfrequenz einzelner Variablen und Variablenpaare wurden analysiert.

Ergebnisse

Mit dem progressionsfreien Überleben (PFS) und dem Gesamtüberleben (OS) waren 9 bzw. 10 VASARI-Eigenschaften in der univariaten Analyse signifikant assoziiert. Die Vorhersagekraft der multivariaten Modelle (klinisch, Bildgebung, kombiniert, kombiniert + MGMT) waren mit Konkordanzindizes von je 0,657, 0,636, 0,694 und 0,716 für OS und 0,602, 0,604, 0,633 und 0,643 für PFS signifikant besser als der Zufall. Die Eigenschaften „Multilokalität“, „Invasion tiefer weißer Hirnstrukturen“, „Satellitenherde“ und „ependymale Invasion“ wurden überproportional für die Generierung der multivariaten Modelle selektiert und unterstreichen deren Bedeutung.

Schlussfolgerung

Wir konnten für die VASARI-Eigenschaften eine prädiktive Vorhersagekraft für PFS und OS nachweisen. Die Vorhersagekraft multivariabler Modelle wurde durch Hinzunahme von klinischen und pathologischen Informationen verbessert.

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Funding

The work was funded in part by Deutsches Konsortium für Translationale Krebsforschung (DKTK), Partner Site Munich.

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Authors and Affiliations

  1. Department of Radiation Oncology, Klinikum rechts der Isar, Technical University Munich (TUM), Ismaninger Straße 22, 81675, Munich, Germany

    Jan C. Peeken, Josefine Hesse, Kerstin A. Kessel, Fridtjof Nüsslin & Stephanie E. Combs

  2. Institute of Innovative Radiotherapy (iRT), Department of Radiation Sciences (DRS), Helmholtz Zentrum München, Ingolstaedter Landstraße 1, 85764, Neuherberg, Germany

    Stephanie E. Combs

  3. Institut for Medical Statistics and Epidemiology, Technical University Munich (TUM), Ismaninger Straße 22, 81675, Munich, Germany

    Bernhard Haller & Kerstin A. Kessel

  4. Deutsches Konsortium für Translationale Krebsforschung (DKTK), Partner Site Munich, Munich, Germany

    Jan C. Peeken, Kerstin A. Kessel & Stephanie E. Combs

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  1. Jan C. Peeken
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Correspondence to Jan C. Peeken.

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Conflict of interest

J.C. Peeken, J. Hesse, B. Haller, K.A. Kessel, F. Nüsslin, and S.E. Combs declare that they have no competing interests.

Ethical standards

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975 (in its most recently amended version). Informed consent was obtained from all patients included in the study.

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Peeken, J.C., Hesse, J., Haller, B. et al. Semantic imaging features predict disease progression and survival in glioblastoma multiforme patients. Strahlenther Onkol 194, 580–590 (2018). https://doi.org/10.1007/s00066-018-1276-4

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