Makoto Kiyose1,2,3,4, Eva Herrmann5, Jenny Roesler6, Pia S Zeiner2,3,4,7,8,9, Joachim P Steinbach3,4,7,8,9, Marie-Therese Forster10, Karl H Plate6,8,9, Marcus Czabanka10, Thomas J Vogl11, Elke Hattingen1, Michel Mittelbronn6,12,13,14,15,16,17, Stella Breuer1, Patrick N Harter6,8,9, Simon Bernatz18,19,20,21. 1. Institute of Neuroradiology, University Hospital, Goethe University, Frankfurt am Main, Germany. 2. Department of Neurology, University Hospital, Frankfurt am Main, Germany. 3. Frankfurt Cancer Institute (FCI), Goethe University, Frankfurt am Main, Germany. 4. University Cancer Center Frankfurt (UCT), University Hospital, Goethe University, 60590, Frankfurt am Main, Germany. 5. Institute for Biostatistics and Mathematical Modelling, University Hospital, Frankfurt am Main, Germany. 6. Neurological Institute (Edinger Institute), University Hospital, Frankfurt, Frankfurt am Main, Germany. 7. Senckenberg Institute of Neurooncology, University Hospital, Frankfurt am Main, Germany. 8. German Cancer Consortium (DKTK), Heidelberg, Germany. 9. German Cancer Research Centre (DKFZ), Heidelberg, Germany. 10. Department of Neurosurgery, Goethe University, Frankfurt am Main, Germany. 11. Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Goethe University Frankfurt Am Main, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany. 12. Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg. 13. Laboratoire National de Santé (LNS), Dudelange, Luxembourg. 14. Luxembourg Center of Neuropathology (LCNP), Dudelange, Luxembourg. 15. Department of Cancer Research (DoCR), Luxembourg Institute of Health (L.I.H.), Luxembourg, Luxembourg. 16. Department of Life Sciences and Medicine (DLSM), University of Luxembourg, Esch-sur-Alzette, Luxembourg. 17. Faculty of Science, Technology and Medicine (FSTM)S, University of Luxembourg, Esch-sur-Alzette, Luxembourg. 18. Frankfurt Cancer Institute (FCI), Goethe University, Frankfurt am Main, Germany. Simon.Bernatz@kgu.de. 19. University Cancer Center Frankfurt (UCT), University Hospital, Goethe University, 60590, Frankfurt am Main, Germany. Simon.Bernatz@kgu.de. 20. Neurological Institute (Edinger Institute), University Hospital, Frankfurt, Frankfurt am Main, Germany. Simon.Bernatz@kgu.de. 21. Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Goethe University Frankfurt Am Main, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany. Simon.Bernatz@kgu.de.
Abstract
PURPOSE: Non-invasive prediction of the tumour of origin giving rise to brain metastases (BMs) using MRI measurements obtained in radiological routine and elucidating the biological basis by matched histopathological analysis. METHODS: Preoperative MRI and histological parameters of 95 BM patients (female, 50; mean age 59.6 ± 11.5 years) suffering from different primary tumours were retrospectively analysed. MR features were assessed by region of interest (ROI) measurements of signal intensities on unenhanced T1-, T2-, diffusion-weighted imaging and apparent diffusion coefficient (ADC) normalised to an internal reference ROI. Furthermore, we assessed BM size and oedema as well as cell density, proliferation rate, microvessel density and vessel area as histopathological parameters. RESULTS: Applying recursive partitioning conditional inference trees, only histopathological parameters could stratify the primary tumour entities. We identified two distinct BM growth patterns depending on their proliferative status: Ki67high BMs were larger (p = 0.02), showed less peritumoural oedema (p = 0.02) and showed a trend towards higher cell density (p = 0.05). Furthermore, Ki67high BMs were associated with higher DWI signals (p = 0.03) and reduced ADC values (p = 0.004). Vessel density was strongly reduced in Ki67high BM (p < 0.001). These features differentiated between lung cancer BM entities (p ≤ 0.03 for all features) with SCLCs representing predominantly the Ki67high group, while NSCLCs rather matching with Ki67low features. CONCLUSION: Interpretable and easy to obtain MRI features may not be sufficient to predict directly the primary tumour entity of BM but seem to have the potential to aid differentiating high- and low-proliferative BMs, such as SCLC and NSCLC.
PURPOSE: Non-invasive prediction of the tumour of origin giving rise to brain metastases (BMs) using MRI measurements obtained in radiological routine and elucidating the biological basis by matched histopathological analysis. METHODS: Preoperative MRI and histological parameters of 95 BM patients (female, 50; mean age 59.6 ± 11.5 years) suffering from different primary tumours were retrospectively analysed. MR features were assessed by region of interest (ROI) measurements of signal intensities on unenhanced T1-, T2-, diffusion-weighted imaging and apparent diffusion coefficient (ADC) normalised to an internal reference ROI. Furthermore, we assessed BM size and oedema as well as cell density, proliferation rate, microvessel density and vessel area as histopathological parameters. RESULTS: Applying recursive partitioning conditional inference trees, only histopathological parameters could stratify the primary tumour entities. We identified two distinct BM growth patterns depending on their proliferative status: Ki67high BMs were larger (p = 0.02), showed less peritumoural oedema (p = 0.02) and showed a trend towards higher cell density (p = 0.05). Furthermore, Ki67high BMs were associated with higher DWI signals (p = 0.03) and reduced ADC values (p = 0.004). Vessel density was strongly reduced in Ki67high BM (p < 0.001). These features differentiated between lung cancer BM entities (p ≤ 0.03 for all features) with SCLCs representing predominantly the Ki67high group, while NSCLCs rather matching with Ki67low features. CONCLUSION: Interpretable and easy to obtain MRI features may not be sufficient to predict directly the primary tumour entity of BM but seem to have the potential to aid differentiating high- and low-proliferative BMs, such as SCLC and NSCLC.
Authors: J A Calvar; F J Meli; C Romero; M L Calcagno; P Yánez; A R Martinez; H Lambre; A L Taratuto; G Sevlever Journal: J Neurooncol Date: 2005-05 Impact factor: 4.130
Authors: Thomas Spanberger; Anna S Berghoff; Carina Dinhof; Aysegül Ilhan-Mutlu; Manuel Magerle; Markus Hutterer; Josef Pichler; Adelheid Wöhrer; Monika Hackl; Georg Widhalm; Johannes A Hainfellner; Karin Dieckmann; Christine Marosi; Peter Birner; Daniela Prayer; Matthias Preusser Journal: Clin Exp Metastasis Date: 2012-10-17 Impact factor: 5.150
Authors: H R Arvinda; C Kesavadas; P S Sarma; B Thomas; V V Radhakrishnan; A K Gupta; T R Kapilamoorthy; S Nair Journal: J Neurooncol Date: 2009-02-20 Impact factor: 4.130