ORCID Profile
0000-0003-2476-178X
Current Organisation
Universitätsklinikum Tübingen
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Publisher: Springer Science and Business Media LLC
Date: 24-10-2023
Publisher: Cold Spring Harbor Laboratory
Date: 23-07-2021
DOI: 10.1101/2021.07.22.21260982
Abstract: High grade serous ovarian cancer (HGSOC) is a highly heterogeneous disease that often presents at an advanced, metastatic state. The multi-scale complexity of HGSOC is a major obstacle to measuring response to neoadjuvant chemotherapy (NACT) and understanding its determinants. Here we propose a radiogenomic framework integrating clinical, radiomic, and blood-based biomarkers to measure and predict the response of HGSOC patients to NACT, showing how quantitative imaging data can serve as the backbone of multi-scale data integration. We developed and validated our approach in two independent highly-annotated multi-omic multi-lesion data sets. In a discovery cohort (n=72) we found that different tumour sites present distinct response patterns, and identified volumetric response assessment as a better predictor of overall survival (OS) than RECIST 1.1 status. We trained an ensemble machine learning approach to predict tumour volume response to NACT from data obtained prior to treatment, and validated the model in an internal hold-out cohort (n=20) and an independent external patient cohort (n=42). Benchmarking integrated models against models built on single data types highlighted the importance of comprehensive patient characterisation. Our study sets the foundation for developing new clinical trials of NACT in HGSOC.
Publisher: Springer Science and Business Media LLC
Date: 28-02-2020
DOI: 10.1186/S13073-020-00723-8
Abstract: Cell-free tumor-derived DNA (ctDNA) allows non-invasive monitoring of cancers, but its utility in renal cell cancer (RCC) has not been established. Here, a combination of untargeted and targeted sequencing methods, applied to two independent cohorts of patients ( n = 91) with various renal tumor subtypes, were used to determine ctDNA content in plasma and urine. Our data revealed lower plasma ctDNA levels in RCC relative to other cancers of similar size and stage, with untargeted detection in 27.5% of patients from both cohorts. A sensitive personalized approach, applied to plasma and urine from select patients ( n = 22) improved detection to ~ 50%, including in patients with early-stage disease and even benign lesions. Detection in plasma, but not urine, was more frequent amongst patients with larger tumors and in those patients with venous tumor thrombus. With data from one extensively characterized patient, we observed that plasma and, for the first time, urine ctDNA may better represent tumor heterogeneity than a single tissue biopsy. Furthermore, in a subset of patients ( n = 16), longitudinal s ling revealed that ctDNA can track disease course and may pre-empt radiological identification of minimal residual disease or disease progression on systemic therapy. Additional datasets will be required to validate these findings. These data highlight RCC as a ctDNA-low malignancy. The biological reasons for this are yet to be determined. Nonetheless, our findings indicate potential clinical utility in the management of patients with renal tumors, provided improvement in isolation and detection approaches.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Stephan Ursprung.