HR-SC-an academic-developed machine learning framework to classify HRD-positive ovarian cancer patients and predict sensitivity to olaparib.

Journal: ESMO open
Published Date:

Abstract

BACKGROUND: High-grade serous ovarian cancer (OC) patients with defects in the homologous recombination repair (HRR) pathway benefit from poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance therapy. Clinically approved methods for identifying HRR status suffer from limitations, such as high failure rates and costs, leading to the clinical need for innovative approaches. To this aim, we developed Homologous Recombination Signature Classifier (HR-SC), a machine learning (ML) algorithm that integrates BRCA1/BRCA2 status and copy number signatures, leveraging the availability of OC samples recruited from two international clinical trials, namely PAOLA-1 (dataset A) and MITO16A/MaNGO-OV2 (dataset B).

Authors

  • L Beltrame
    Laboratory of Cancer Pharmacology, IRCCS Humanitas Research Hospital, Rozzano, Italy.
  • L Mannarino
    Laboratory of Cancer Pharmacology, IRCCS Humanitas Research Hospital, Rozzano, Italy; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy.
  • A Sergi
    Laboratory of Cancer Pharmacology, IRCCS Humanitas Research Hospital, Rozzano, Italy; Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy.
  • A Velle
    Department of Biology, University of Padova, Padova, Italy.
  • I Treilleux
    Biopathology Department, Centre Léon Bérard, Lyon, France.
  • S Pignata
    Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G Pascale, Naples, Italy.
  • L Paracchini
    Laboratory of Cancer Pharmacology, IRCCS Humanitas Research Hospital, Rozzano, Italy; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy.
  • P Harter
    Department of Gynecology & Gynecologic Oncology, Evang. Kliniken Essen-Mitte, Essen, Germany.
  • G Scambia
    Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy.
  • F Perrone
    Clinical Trial Unit, Istituto Nazionale Tumori IRCCS Fondazione G Pascale, Naples, Italy.
  • A González-Martin
    Clínica Universidad de Navarra, Madrid, Spain; Spanish Ovarian Cancer Research Group (GEICO), Madrid, Spain.
  • R Berger
    Department of Obstetrics and Gynecology, Medical University Innsbruck, Innsbruck, Austria; AGO Austria Study Center, Vienna, Austria.
  • L Arenare
    Clinical Trial Unit, Istituto Nazionale Tumori IRCCS Fondazione G Pascale, Naples, Italy.
  • S Hietanen
    Turku University Hospital, Turku, Finland; Nordic Society of Gynaecological Oncology (NSGO-CTU), Copenhagen, Denmark.
  • D Califano
    Microenvironment Molecular Targets Unit, Istituto Nazionale Tumori IRCCS Fondazione G Pascale, Naples, Italy.
  • S Derio
    Instituto Europeo di Oncologia, Milan, Italy; Mario Negri Gynecologic Oncology (MaNGO) Group, Milan, Italy.
  • T Van Gorp
    University Hospital of Leuven, Leuven Cancer Institute, Leuven, Belgium; Belgium and Luxemburg Gynaecological Oncology Group (BGOG), Leuven, Belgium.
  • M L Dalessandro
    Laboratory of Cancer Pharmacology, IRCCS Humanitas Research Hospital, Rozzano, Italy.
  • K Fujiwara
    Saitama Medical University International Medical Center, Hidaka, Japan; Gynaecological Oncology Trial and Investigation Consortium (GOTIC), Saitama, Japan.
  • M Provansal
    Institut Paoli Calmettes, Marseille, France; Groupe d'Investigateurs Nationaux Pour l'Etude des Cancers Ovariens (GINECO), Paris, France.
  • D Lorusso
    Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy; Gynaecological Oncology Unit, Humanitas Hospital San Pio X, Milan, Italy.
  • P Buderath
    Universitätsklinikum Essen, Frauenklinik, Essen, Germany.
  • M Masseroli
  • I Ray-Coquard
    Groupe d'Investigateurs Nationaux Pour l'Etude des Cancers Ovariens (GINECO), Paris, France; Centre Léon Bérard, Lyon, France; University Claude Bernard Lyon I, Lyon, France.
  • E Pujade-Lauraine
    ARCAGY Research, Paris, France.
  • C Romualdi
    Department of Biology, University of Padova, Padova, Italy.
  • M D'Incalci
    Laboratory of Cancer Pharmacology, IRCCS Humanitas Research Hospital, Rozzano, Italy; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy. Electronic address: maurizio.dincalci@hunimed.eu.
  • S Marchini
    Laboratory of Cancer Pharmacology, IRCCS Humanitas Research Hospital, Rozzano, Italy.

Keywords

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