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Abstract
High grade serous ovarian carcinoma (HGSOC) is a highly heterogeneous disease that typically presents at an advanced, metastatic state. The multi-scale complexity of HGSOC is a major obstacle to predicting response to neoadjuvant chemotherapy (NACT) and understanding critical determinants of response. Here we present a framework to predict the response of HGSOC patients to NACT integrating baseline clinical, blood-based, and radiomic biomarkers extracted from all primary and metastatic lesions. We use an ensemble machine learning model trained to predict the change in total disease volume using data obtained at diagnosis (n = 72). The model is validated in an internal hold-out cohort (n = 20) and an independent external patient cohort (n = 42). In the external cohort the integrated radiomics model reduces the prediction error by 8% with respect to the clinical model, achieving an AUC of 0.78 for RECIST 1.1 classification compared to 0.47 for the clinical model. Our results emphasize the value of including radiomics data in integrative models of treatment response and provide methods for developing new biomarker-based clinical trials of NACT in HGSOC.
Response to treatment in high grade serous ovarian carcinoma (HGSOC) is highly variable. Here, the authors leverage a radiogenomic model to predict neoadjuvant chemotherapy response in HGSOC, including clinical data, medical imaging, and blood-based biomarkers such as CA-125 and ctDNA features.
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Details
; Woitek, Ramona 2
; Reinius, Marika A. V. 3
; Moore, Elizabeth 4 ; Beer, Lucian 5
; Bura, Vlad 6 ; Rundo, Leonardo 7 ; McCague, Cathal 8
; Ursprung, Stephan 6
; Escudero Sanchez, Lorena 6
; Martin-Gonzalez, Paula 9 ; Mouliere, Florent 10
; Chandrananda, Dineika 4
; Morris, James 4 ; Goranova, Teodora 4 ; Piskorz, Anna M. 4 ; Singh, Naveena 11 ; Sahdev, Anju 12
; Pintican, Roxana 13 ; Zerunian, Marta 14 ; Rosenfeld, Nitzan 9
; Addley, Helen 8 ; Jimenez-Linan, Mercedes 15 ; Markowetz, Florian 9
; Sala, Evis 16 ; Brenton, James D. 3
1 University of Cambridge, Department of Oncology, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000 0001 2188 5934); University of Cambridge, Cancer Research UK Cambridge Centre, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934)
2 University of Cambridge, Cancer Research UK Cambridge Centre, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934); University of Cambridge, Department of Radiology, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000 0001 2188 5934); Danube Private University, Centre for Medical Image Analysis and AI (MIAAI), Krems, Austria (GRID:grid.465811.f) (ISNI:0000 0004 4904 7440)
3 University of Cambridge, Cancer Research UK Cambridge Centre, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934); University of Cambridge, Cancer Research UK Cambridge Institute, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934); Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK (GRID:grid.24029.3d) (ISNI:0000 0004 0383 8386)
4 University of Cambridge, Cancer Research UK Cambridge Institute, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934)
5 University of Cambridge, Cancer Research UK Cambridge Centre, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934); University of Cambridge, Department of Radiology, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000 0001 2188 5934); Medical University of Vienna, Department of Biomedical Imaging and Image-guided Therapy, Vienna, Austria (GRID:grid.22937.3d) (ISNI:0000 0000 9259 8492)
6 University of Cambridge, Cancer Research UK Cambridge Centre, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934); University of Cambridge, Department of Radiology, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000 0001 2188 5934)
7 University of Cambridge, Cancer Research UK Cambridge Centre, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934); University of Cambridge, Department of Radiology, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000 0001 2188 5934); University of Salerno, Department of Information and Electrical Engineering and Applied Mathematics, Fisciano, Italy (GRID:grid.11780.3f) (ISNI:0000 0004 1937 0335)
8 University of Cambridge, Cancer Research UK Cambridge Centre, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934); University of Cambridge, Department of Radiology, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000 0001 2188 5934); Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK (GRID:grid.24029.3d) (ISNI:0000 0004 0383 8386)
9 University of Cambridge, Cancer Research UK Cambridge Centre, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934); University of Cambridge, Cancer Research UK Cambridge Institute, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934)
10 University of Cambridge, Cancer Research UK Cambridge Institute, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934); Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Pathology, Amsterdam, The Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227)
11 Barts Health NHS Trust, Department of Cellular Pathology, London, UK (GRID:grid.139534.9) (ISNI:0000 0001 0372 5777)
12 Barts Health NHS Trust, Department of Radiology, London, UK (GRID:grid.139534.9) (ISNI:0000 0001 0372 5777)
13 “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania (GRID:grid.411040.0) (ISNI:0000 0004 0571 5814); County Clinical Emergency Hospital, Department of Radiology, Cluj-Napoca, Romania (GRID:grid.411040.0)
14 Sapienza University of Rome-Sant’Andrea University Hospital, Department of Surgical and Medical Sciences and Translational Medicine, Rome, Italy (GRID:grid.7841.a)
15 University of Cambridge, Cancer Research UK Cambridge Centre, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934); Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK (GRID:grid.24029.3d) (ISNI:0000 0004 0383 8386)
16 University of Cambridge, Cancer Research UK Cambridge Centre, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934); University of Cambridge, Department of Radiology, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000 0001 2188 5934); Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK (GRID:grid.24029.3d) (ISNI:0000 0004 0383 8386); Universita Cattolica del Sacro Cuore, Dipartimento di Scienze Radiologiche ed Ematologiche, Rome, Italy (GRID:grid.8142.f) (ISNI:0000 0001 0941 3192); Policlinico Universitario A. Gemelli IRCCS, Dipartimento Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Rome, Italy (GRID:grid.411075.6) (ISNI:0000 0004 1760 4193); Western Balkans University, Tirana, Albania (GRID:grid.411075.6)




