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Integrated radiogenomics models predict response to neoadjuvant chemotherapy in high grade serous ovarian cancer

Author

Listed:
  • Mireia Crispin-Ortuzar

    (University of Cambridge
    University of Cambridge)

  • Ramona Woitek

    (University of Cambridge
    University of Cambridge
    Danube Private University)

  • Marika A. V. Reinius

    (University of Cambridge
    University of Cambridge
    Cambridge University Hospitals NHS Foundation Trust)

  • Elizabeth Moore

    (University of Cambridge)

  • Lucian Beer

    (University of Cambridge
    University of Cambridge
    Medical University of Vienna)

  • Vlad Bura

    (University of Cambridge
    University of Cambridge)

  • Leonardo Rundo

    (University of Cambridge
    University of Cambridge
    University of Salerno)

  • Cathal McCague

    (University of Cambridge
    University of Cambridge
    Cambridge University Hospitals NHS Foundation Trust)

  • Stephan Ursprung

    (University of Cambridge
    University of Cambridge)

  • Lorena Escudero Sanchez

    (University of Cambridge
    University of Cambridge)

  • Paula Martin-Gonzalez

    (University of Cambridge
    University of Cambridge)

  • Florent Mouliere

    (University of Cambridge
    Amsterdam UMC location Vrije Universiteit Amsterdam)

  • Dineika Chandrananda

    (University of Cambridge)

  • James Morris

    (University of Cambridge)

  • Teodora Goranova

    (University of Cambridge)

  • Anna M. Piskorz

    (University of Cambridge)

  • Naveena Singh

    (Barts Health NHS Trust)

  • Anju Sahdev

    (Barts Health NHS Trust)

  • Roxana Pintican

    (“Iuliu Hatieganu” University of Medicine and Pharmacy
    County Clinical Emergency Hospital)

  • Marta Zerunian

    (Sapienza University of Rome-Sant’Andrea University Hospital)

  • Nitzan Rosenfeld

    (University of Cambridge
    University of Cambridge)

  • Helen Addley

    (University of Cambridge
    University of Cambridge
    Cambridge University Hospitals NHS Foundation Trust)

  • Mercedes Jimenez-Linan

    (University of Cambridge
    Cambridge University Hospitals NHS Foundation Trust)

  • Florian Markowetz

    (University of Cambridge
    University of Cambridge)

  • Evis Sala

    (University of Cambridge
    University of Cambridge
    Cambridge University Hospitals NHS Foundation Trust
    Universita Cattolica del Sacro Cuore)

  • James D. Brenton

    (University of Cambridge
    University of Cambridge
    Cambridge University Hospitals NHS Foundation Trust)

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.

Suggested Citation

  • Mireia Crispin-Ortuzar & Ramona Woitek & Marika A. V. Reinius & Elizabeth Moore & Lucian Beer & Vlad Bura & Leonardo Rundo & Cathal McCague & Stephan Ursprung & Lorena Escudero Sanchez & Paula Martin-, 2023. "Integrated radiogenomics models predict response to neoadjuvant chemotherapy in high grade serous ovarian cancer," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41820-7
    DOI: 10.1038/s41467-023-41820-7
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    1. Viktor A. Adalsteinsson & Gavin Ha & Samuel S. Freeman & Atish D. Choudhury & Daniel G. Stover & Heather A. Parsons & Gregory Gydush & Sarah C. Reed & Denisse Rotem & Justin Rhoades & Denis Loginov & , 2017. "Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    2. Peter Ulz & Samantha Perakis & Qing Zhou & Tina Moser & Jelena Belic & Isaac Lazzeri & Albert Wölfler & Armin Zebisch & Armin Gerger & Gunda Pristauz & Edgar Petru & Brandon White & Charles E. S. Robe, 2019. "Inference of transcription factor binding from cell-free DNA enables tumor subtype prediction and early detection," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    3. Cheng Ju & Aurélien Bibaut & Mark van der Laan, 2018. "The relative performance of ensemble methods with deep convolutional neural networks for image classification," Journal of Applied Statistics, Taylor & Francis Journals, vol. 45(15), pages 2800-2818, November.
    4. Ann-Marie Patch & Elizabeth L. Christie & Dariush Etemadmoghadam & Dale W. Garsed & Joshy George & Sian Fereday & Katia Nones & Prue Cowin & Kathryn Alsop & Peter J. Bailey & Karin S. Kassahn & Felici, 2015. "Whole–genome characterization of chemoresistant ovarian cancer," Nature, Nature, vol. 521(7553), pages 489-494, May.
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