Tumor grading of soft tissue sarcomas using MRI-based radiomicsResearch in context
Jan C. Peeken,
Matthew B. Spraker,
Carolin Knebel,
Hendrik Dapper,
Daniela Pfeiffer,
Michal Devecka,
Ahmed Thamer,
Mohamed A. Shouman,
Armin Ott,
Rüdiger von Eisenhart-Rothe,
Fridtjof Nüsslin,
Nina A. Mayr,
Matthew J. Nyflot,
Stephanie E. Combs
Affiliations
Jan C. Peeken
Department of Radiation Oncology, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich (TUM), Ismaninger Straße 22, 81675 Munich, Germany; Institute of Radiation Medicine (IRM), Department of Radiation Sciences (DRS), Helmholtz Zentrum München, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany; Deutsches Konsortium für Translationale Krebsforschung (DKTK), Partner Site Munich, Germany; Corresponding author at: Department of Radiation Oncology, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich (TUM), Ismaninger Straße 22, 81675 Munich, Germany.
Matthew B. Spraker
Department of Radiation Oncology, University of Washington, 1959 NE Pacific St, Box 356043, Seattle, WA 98195, United States of America
Carolin Knebel
Department of Orthopaedic Surgery, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich (TUM), Ismaninger Straße 22, 81675 München, Germany
Hendrik Dapper
Department of Radiation Oncology, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich (TUM), Ismaninger Straße 22, 81675 Munich, Germany
Daniela Pfeiffer
Department of Radiology, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich (TUM), Ismaninger Straße 22, 81675 Munich, Germany
Michal Devecka
Department of Radiation Oncology, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich (TUM), Ismaninger Straße 22, 81675 Munich, Germany
Ahmed Thamer
Department of Radiation Oncology, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich (TUM), Ismaninger Straße 22, 81675 Munich, Germany
Mohamed A. Shouman
Department of Radiation Oncology, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich (TUM), Ismaninger Straße 22, 81675 Munich, Germany
Armin Ott
Institute of Medical Informatics, Statistics and Epidemiology, Technical University of Munich (TUM), Ismaninger Straße 22, 81675 Munich, Germany
Rüdiger von Eisenhart-Rothe
Department of Orthopaedic Surgery, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich (TUM), Ismaninger Straße 22, 81675 München, Germany
Fridtjof Nüsslin
Department of Radiation Oncology, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich (TUM), Ismaninger Straße 22, 81675 Munich, Germany
Nina A. Mayr
Department of Radiation Oncology, University of Washington, 1959 NE Pacific St, Box 356043, Seattle, WA 98195, United States of America
Matthew J. Nyflot
Department of Radiation Oncology, University of Washington, 1959 NE Pacific St, Box 356043, Seattle, WA 98195, United States of America; Department of Radiology, University of Washington, Seattle, WA, United States of America
Stephanie E. Combs
Department of Radiation Oncology, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich (TUM), Ismaninger Straße 22, 81675 Munich, Germany; Institute of Radiation Medicine (IRM), Department of Radiation Sciences (DRS), Helmholtz Zentrum München, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany; Deutsches Konsortium für Translationale Krebsforschung (DKTK), Partner Site Munich, Germany
Background: Treatment decisions for multimodal therapy in soft tissue sarcoma (STS) patients greatly depend on the differentiation between low-grade and high-grade tumors. We developed MRI-based radiomics grading models for the differentiation between low-grade (G1) and high-grade (G2/G3) STS. Methods: The study was registered at ClinicalTrials.gov (number NCT03798795). Contrast-enhanced T1-weighted fat saturated (T1FSGd), fat-saturated T2-weighted (T2FS) MRI sequences, and tumor grading following the French Federation of Cancer Centers Sarcoma Group obtained from pre-therapeutic biopsies were gathered from two independent retrospective patient cohorts. Volumes of interest were manually segmented. After preprocessing, 1394 radiomics features were extracted from each sequence. Features unstable in 21 independent multiple-segmentations were excluded. Least absolute shrinkage and selection operator models were developed using nested cross-validation on a training patient cohort (122 patients). The influence of ComBatHarmonization was assessed for correction of batch effects. Findings: Three radiomic models based on T2FS, T1FSGd and a combined model achieved predictive performances with an area under the receiver operator characteristic curve (AUC) of 0.78, 0.69, and 0.76 on the independent validation set (103 patients), respectively. The T2FS-based model showed the best reproducibility. The radiomics model involving T1FSGd-based features achieved significant patient stratification. Combining the T2FS radiomic model into a nomogram with clinical staging improved prognostic performance and the clinical net benefit above clinical staging alone. Interpretation: MRI-based radiomics tumor grading models effectively classify low-grade and high-grade soft tissue sarcomas. Fund: The authors received support by the medical faculty of the Technical University of Munich and the German Cancer Consortium. Keywords: Soft tissue sarcoma, Radiomics, Tumor grading, MRI, Risk stratification, Biomarker
