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Thaiss, W.M.* ; Gatidis, S.* ; Sartorius, T. ; Machann, J. ; Peter, A. ; Eigentler, T.K.* ; Nikolaou, K.* ; Pichler, B.J.* ; Kneilling, M.*

Noninvasive, longitudinal imaging-based analysis of body adipose tissue and water composition in a melanoma mouse model and in immune checkpoint inhibitor-treated metastatic melanoma patients.

Cancer Immunol. Immunother. 70, 1263-1275 (2021)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Background As cancer cachexia (CC) is associated with cancer progression, early identification would be beneficial. The aim of this study was to establish a workflow for automated MRI-based segmentation of visceral (VAT) and subcutaneous adipose tissue (SCAT) and lean tissue water (LTW) in a B16 melanoma animal model, monitor diseases progression and transfer the protocol to human melanoma patients for therapy assessment. Methods For in vivo monitoring of CC B16 melanoma-bearing and healthy mice underwent longitudinal three-point DIXON MRI (days 3, 12, 17 after subcutaneous tumor inoculation). In a prospective clinical study, 18 metastatic melanoma patients underwent MRI before, 2 and 12 weeks after onset of checkpoint inhibitor therapy (CIT; n = 16). We employed an in-house MATLAB script for automated whole-body segmentation for detection of VAT, SCAT and LTW. Results B16 mice exhibited a CC phenotype and developed a reduced VAT volume compared to baseline (B16 - 249.8 mu l, - 25%; controls + 85.3 mu l, + 10%, p = 0.003) and to healthy controls. LTW was increased in controls compared to melanoma mice. Five melanoma patients responded to CIT, 7 progressed, and 6 displayed a mixed response. Responding patients exhibited a very limited variability in VAT and SCAT in contrast to others. Interestingly, the LTW was decreased in CIT responding patients (- 3.02% +/- 2.67%; p = 0.0034) but increased in patients with progressive disease (+ 1.97% +/- 2.19%) and mixed response (+ 4.59% +/- 3.71%). Conclusion MRI-based segmentation of fat and water contents adds essential additional information for monitoring the development of CC in mice and metastatic melanoma patients during CIT or other treatment approaches.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Melanoma ; Cancer Cachexia ; Mri ; Segmentation ; Therapy Monitoring ; Immune Checkpoint Inhibitor Therapy; Automated Segmentation; Fat; Mri; Pathophysiology; Mechanisms; 2-point; 3-point; White; Brown
ISSN (print) / ISBN 0340-7004
e-ISSN 1432-0851
Zeitschrift Cancer Immunology, Immunotherapy
Quellenangaben Band: 70, Heft: 5, Seiten: 1263-1275 Artikelnummer: , Supplement: ,
Verlag Springer
Verlagsort One New York Plaza, Suite 4600, New York, Ny, United States
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research and Metabolic Diseases (IDM)
Förderungen Werner Siemens-Foundation (Zug, Switzerland)
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, Germany's Excellence Strategy -EXC)
Faculty of Medicine of the Eberhard Karls Universitat Tubingen
Projekt DEAL