Non-invasive monitoring of neoadjuvant radiation therapy response in soft tissue sarcomas by multiparametric MRI and quantification of circulating tumor DNA-A study protocol.

Autor: Runkel A; Faculty of Medicine, Department of Plastic and Hand Surgery, Medical Center-University of Freiburg, Freiburg, Germany.; Faculty of Medicine, Berta-Ottenstein-Programme, University of Freiburg, Freiburg, Germany., Braig D; Faculty of Medicine, Department of Plastic and Hand Surgery, Medical Center-University of Freiburg, Freiburg, Germany.; Division of Hand, Plastic and Aesthetic Surgery, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany., Bogner B; Faculty of Medicine, Department of Radiology, Medical Center-University of Freiburg, Freiburg, Germany., Schmid A; Faculty of Medicine, Department of Plastic and Hand Surgery, Medical Center-University of Freiburg, Freiburg, Germany., Lausch U; Faculty of Medicine, Department of Plastic and Hand Surgery, Medical Center-University of Freiburg, Freiburg, Germany., Boneberg A; Faculty of Medicine, Department of Plastic and Hand Surgery, Medical Center-University of Freiburg, Freiburg, Germany., Brugger Z; Faculty of Medicine, Department of Medicine I, Medical Center-University of Freiburg, Freiburg, Germany., Eisenhardt A; Faculty of Medicine, Department of Plastic and Hand Surgery, Medical Center-University of Freiburg, Freiburg, Germany., Kiefer J; Faculty of Medicine, Department of Plastic and Hand Surgery, Medical Center-University of Freiburg, Freiburg, Germany., Pauli T; Faculty of Medicine, Institute of Medical Bioinformatics, Medical Center-University of Freiburg, Freiburg, Germany., Boerries M; Faculty of Medicine, Institute of Medical Bioinformatics, Medical Center-University of Freiburg, Freiburg, Germany., Fuellgraf H; Faculty of Medicine, Institute of Surgical Pathology, Medical Center-University of Freiburg, Freiburg, Germany., Kurowski K; Faculty of Medicine, Institute of Surgical Pathology, Medical Center-University of Freiburg, Freiburg, Germany., Bronsert P; Faculty of Medicine, Institute of Surgical Pathology, Medical Center-University of Freiburg, Freiburg, Germany.; Tumorbank Comprehensive Cancer Center Freiburg, Medical Center-University of Freiburg, Freiburg, Germany.; Core Facility for Histopathology and Digital Pathology, Medical Center-University of Freiburg, Freiburg, Germany., Scholber J; Faculty of Medicine, Department of Radiation Oncology, Medical Center-University of Freiburg, Freiburg, Germany., Grosu AL; Faculty of Medicine, Department of Radiation Oncology, Medical Center-University of Freiburg, Freiburg, Germany., Rovedo P; Faculty of Medicine, Department of Radiology, Medical Physics, Medical Center-University of Freiburg, Freiburg, Germany., Bamberg F; Faculty of Medicine, Department of Radiology, Medical Center-University of Freiburg, Freiburg, Germany., Eisenhardt SU; Faculty of Medicine, Department of Plastic and Hand Surgery, Medical Center-University of Freiburg, Freiburg, Germany., Jung M; Faculty of Medicine, Berta-Ottenstein-Programme, University of Freiburg, Freiburg, Germany.; Faculty of Medicine, Department of Radiology, Medical Center-University of Freiburg, Freiburg, Germany.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2023 Nov 01; Vol. 18 (11), pp. e0285580. Date of Electronic Publication: 2023 Nov 01 (Print Publication: 2023).
DOI: 10.1371/journal.pone.0285580
Abstrakt: Background: Wide resection remains the cornerstone of localized soft-tissue sarcomas (STS) treatment. Neoadjuvant radiation therapy (NRT) may decrease the risk of local recurrences; however, its effectiveness for different histological STS subtypes has not been systematically investigated. The proposed prospective study evaluates the NRT response in STS using liquid biopsies and the correlation of multiparametric magnetic resonance imaging (mpMRI) with histopathology and immunohistochemistry.
Methods: Patients with localized high-grade STS, who qualify for NRT, are included in this study.
Liquid Biopsies: Quantification of circulating tumor DNA (ctDNA) in patient blood samples is performed by targeted next-generation sequencing. Soft-tissue sarcoma subtype-specific panel sequencing in combination with patient-specific exome sequencing allows the detection of individual structural variants and point mutations. Circulating free DNA is isolated from peritherapeutically collected patient plasma samples and ctDNA quantified therein. Identification of breakpoints is carried out using FACTERA. Bioinformatic analysis is performed using samtools, picard, fgbio, and the MIRACUM Pipeline.
Mpmri: Combination of conventional MRI sequences with diffusion-weighted imaging, intravoxel-incoherent motion, and dynamic contrast enhancement. Multiparametric MRI is performed before, during, and after NRT. We aim to correlate mpMRI data with the resected specimen's macroscopical, histological, and immunohistochemical findings.
Results: Preliminary data support the notion that quantification of ctDNA in combination with tumor mass characterization through co-registration of mpMRI and histopathology can predict NRT response of STS.
Clinical Relevance: The methods presented in this prospective study are necessary to assess therapy response in heterogeneous tumors and lay the foundation of future patient- and tumor-specific therapy concepts. These methods can be applied to various tumor entities. Thus, the participation and support of a wider group of oncologic surgeons are needed to validate these findings on a larger patient cohort.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2023 Runkel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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