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Establishment of CORONET: COVID-19 Risk in Oncology Evaluation Tool to Identify Cancer Patients at Low Versus High Risk of Severe Complications of COVID-19 Infection Upon Presentation to Hospital

51 Pages Posted: 28 Jul 2021

See all articles by Rebecca Lee

Rebecca Lee

The Christie NHS Foundation Trust

Oskar Wysocki

University of Manchester

C. Zhou

University of Manchester - Digital Experimental Cancer Medicine

Rohan Shotton

affiliation not provided to SSRN

Ann Tivey

affiliation not provided to SSRN

Louise Lever

University of Manchester

Joshua Woodcock

University of Manchester

Angelos Angelakas

affiliation not provided to SSRN

D. Arnold

ITG, Inc. - ITG London

Theingi Aung

affiliation not provided to SSRN

Kathryn Banfill

affiliation not provided to SSRN

Mark Baxter

University of Dundee

Talvinder Bhogal

affiliation not provided to SSRN

Hayley Boyce

affiliation not provided to SSRN

Fiona Britton

affiliation not provided to SSRN

Antonio Calles

Hospital General Universitario Gregorio Marañón

Louis Castelo-Branco

affiliation not provided to SSRN

Ellen Copson

University of Southampton - University Hospital Southampton NHS Foundation Trust

Adina Croitoru

Fundeni Clinical Institute

Sourbha Dani

affiliation not provided to SSRN

Elena Dickens

affiliation not provided to SSRN

Leonie Eastlake

University Hospitals Plymouth NHS Trust

P. Fitzpatrick

University of Manchester - Digital Experimental Cancer Medicine

H. Frost

University of Manchester - Digital Experimental Cancer Medicine

Sarju Ganatra

affiliation not provided to SSRN

Spyridon Gennatas

affiliation not provided to SSRN

F. Gomes

The Christie NHS Foundation Trust

Donna Graham

affiliation not provided to SSRN

Christina Hague

affiliation not provided to SSRN

Kevin Harrington

NHS Foundation Trust - Royal Marsden Hospital

Michelle Harrison

Ninewells Hospital and Medical School

Laura Horsley

affiliation not provided to SSRN

R. Hoskins

University of Manchester - Research IT

Prerana Huddar

affiliation not provided to SSRN

Zoe Hudson

affiliation not provided to SSRN

Nalinie Joharatnam-Hogan

University College London Hospital

S. Khan

Government of the United Kingdom - Oncology Department

U.T. Khan

Clatterbridge Cancer Centre

Khurum Khan

University College London - UCL Cancer Institute

Alec Maynard

affiliation not provided to SSRN

H. McKenzie

University of Southampton - Cancer Sciences Academic Unit

Olivier Michielin

affiliation not provided to SSRN

Anne Mosenthal

affiliation not provided to SSRN

Berta Obispo

affiliation not provided to SSRN

Rushin Patel

affiliation not provided to SSRN

George pentheroudakis

affiliation not provided to SSRN

solange peters

affiliation not provided to SSRN

Kimberly Rieger-Christ

affiliation not provided to SSRN

T. Robinson

Bristol Haematology and Oncology Centre

Jacobo Rogado

affiliation not provided to SSRN

Emanuela Romano

affiliation not provided to SSRN

M. Rowe

Royal Cornwall Hospital - Sunrise Centre

Marina Sekacheva

I.M. Sechenov First Moscow State Medical University

Roseleen Sheehan

affiliation not provided to SSRN

Julie Stevenson

affiliation not provided to SSRN

Alexander J. Stockdale

National Institute for Health Research (NIHR)

A. Thomas

Government of the United Kingdom - Oncology Department

Lance Turtle

University of Liverpool - NIHR Health Protection Research Unit in Emerging and Zoonotic Infections

D. Viñal

Hospital Universitario La Paz - Department of Medical Oncology

J. Weaver

The Christie NHS Foundation Trust

S. Williams

Government of the United Kingdom - Weston Park Cancer Centre

C. Wilson

Government of the United Kingdom - Weston Park Cancer Centre

Carlo Palmieri

affiliation not provided to SSRN

Donal Landers

affiliation not provided to SSRN

Tim Cooksley

The Christie NHS Foundation Trust

ESMO Co-Care Group

Independent

Caroline Dive

University of Manchester; Cancer Research UK Lung Cancer Centre of Excellence

Andre Freitas

University of Manchester

A. C. Armstrong

The Christie NHS Foundation Trust

More...

Abstract

Background: Patients with cancer are at increased risk of severe COVID-19, but have heterogeneous presentations and outcomes. Decision-making tools for hospital admission, severity prediction and increased monitoring for early intervention are critical. We sought to identify features of COVID-19 in cancer patients predicting severe disease and build a decision-support online tool; COVID-19 Risk in Oncology Evaluation Tool (CORONET).

Methods: Patients with active cancer (stage I-IV) and laboratory confirmed COVID-19 presenting to hospitals worldwide were included. Discharge (within 24hrs), admission (≥24hrs inpatient), oxygen requirement (O2) and death were combined in a 0-3 point severity scale.  Association of features with outcome were investigated using Lasso regression and Random Forest (RF) combined with SHapley Additive exPlanations (SHAP). RF was further validated in 4 cohorts, split by geography. The CORONET model was then examined in the entire cohort to build an online CORONET decision-support tool.  Admission and severe disease thresholds were established through pragmatically defined cost functions.

Findings: The dataset comprised 920 patients; median age 70 (range 5-99), 56% males, 44% females, 81% solid vs. 19% haematological cancers. In derivation, RF demonstrated superior performance over Lasso with lower mean squared error (0.801 vs. 0.807) and was selected for development. During validation, RF achieved mean AUROC 0.77, 0.80 and 0.75 for prediction of admission, O 2 and death, respectively. Using the entire cohort, CORONET cut-offs for admission and mortality of 1.0 and 2.3 were established. The CORONET decision support tool recommended admission for 95% of patients eventually requiring oxygen and 97% of those who died. SHAP explanations revealed National-Early-Warning-Score-2, C-reactive protein and albumin were the most important features contributing to COVID-19 severity prediction in patients with cancer at time of hospital presentation.

Interpretation: CORONET, a decision-support tool validated in healthcare systems worldwide can aid admission decisions and predict COVID-19 severity in patients with cancer.

Funding Information: R. Lee and T. Robinson and J. Weaver are supported by the National Institute for Health Research as Clinical Lecturers. T. Bhogal is supported by the National Institute for Health Research as an academic clinical fellow. U. Khan is an MRC Clinical Training Fellow based at the University of Liverpool supported by the North West England Medical Research Council Fellowship Scheme in Clinical Pharmacology and Therapeutics, which is funded by the Medical Research Council (Award Ref. MR/N025989/1). The Liverpool Experimental Cancer Medicine Centre for providing infrastructure support (Grant Reference: C18616/A25153) and The Clatterbridge Cancer charity (North West Cancer Research). C. Dive is funded by CRUK Core funding to Manchester Institute (C5757/A27412) and is supported by the CRUK Manchester Centre Award (C5759/A25254), and by the NIHR Manchester Biomedical Research Centre. C. Zhou is funded by the CRUK Manchester Centre Award (C5759/A25254), J. Stevenson and P. Fitzpatrick are funded by the CRUK Accelerator Award (29374). This research was funded in part, by the Wellcome Trust [205228/Z/16/Z]. LT is also supported by the National Institute for Health Research Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections (NIHR200907) at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford. LT is based at University of Liverpool. MS is supported by a grant from the Ministry of Science and Higher Education of the Russian Federation for the state support for the creation and development of WorldClass Research Centers "Digital biodesign and personalized healthcare” N.075-15-2020-926.

Declaration of Interests: R Lee research funding (institution) BMS and speaker fees Astrazeneca.

A. Croitoru Consulting or Advisory Role: Lilly, Merck, Roche, Bayer, Novartis, Ipsen, Research Funding me and my hospital: Gilead Sciences, Pfizer, Canfite, NanoCarrier, Bristol-Myers Squibb, Merck, Amgen, Servier, Five Prime Therapeutics, Travel Accommodations: Pfizer, Genekor, and oz, Merck, Pfizer, Servier, Roche.

O. Michielin reports personal fees from Bristol-Myers Squibb, personal fees from MSD, personal fees from Novartis, personal fees from Roche, personal fees from Amgen, personal fees from NeraCare GmbH, outside the submitted work.

E. Romano institutional research grants from Amgen, Astra Zeneca, Bristol-Myers Squibb.

G. Pentheroudakis advisory board for Amgen, Astra Zeneca, Bristol-Myers Squibb, Lilly, Merck, MSD, Roche, Abbvie, institutional research grants from Amgen, Astra Zeneca, Boehringer Ingelheim, Bristol Myers Squibb, Debbio, Enorasis, Genekor, Ipsen, Janssen, Lilly, Merck, MSD, Pfizer, Roche, Sanofi, Servier.

Solange Peters reports consultation/advisory role: AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Biocartis, Bio Invent, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, Elsevier, F. Hoffmann-La Roche/Genentech, Foundation Medicine, Illumina, Incyte, IQVIA, Janssen, Medscape, Merck Sharp and Dohme, Merck Serono, Merrimack, Mirati, Novartis, Pharma Mar, Phosplatin Therapeutics, Pfizer, Regeneron, Sanofi, Seattle Genetics, Takeda, Vaccibody, talk in a company’s organized public event: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, e-cancer, Eli Lilly, F. Hoffmann-La Roche/Genentech, Illumina, Medscape, Merck Sharp and Dohme, Novartis, PER, Pfizer, Prime, RTP, Sanofi, Takeda,
receipt of grants/research supports: (Sub)investigator in trials (institutional financial support for clinical trials) sponsored by Amgen, AstraZeneca, Biodesix, Boehringer Ingelheim, Bristol-Myers
Squibb, Clovis, F. Hoffmann-La Roche/Genentech, GSK, Illumina, Lilly, Merck Sharp and Dohme,
Merck Serono, Mirati, Novartis, and Pfizer, Phosplatin Therapeutics.

M Rowe honoraria from Astellas Pharma, speaker fees MSD and Servier.

C. Wilson consultancy and speaker fees Pfizer, Amgen, Novartis,

A Armstrong conference fee Merck, spouse shares in Astrazeneca.

T Robinson financial support to attend educational workshops from Amgen and Daiichi-Sankyo.

C Dive, outside of this scope of work, has received research funding from AstraZeneca, Astex Pharmaceuticals, Bioven, Amgen, Carrick Therapeutics, Merck AG, Taiho Oncology, Clearbridge Biomedics, Angle PLC, Menarini Diagnostics, GSK, Bayer, Boehringer Ingelheim, Roche, BMS, Novartis, Celgene, Thermofisher. C Dive is on advisory boards for, and has received consultancy fees/honoraria from, AstraZeneca, Biocartis and Merck KGaA.

No other authors have nothing to declare.

Ethics Approval Statement: Approval (reference 20/WA/0269) was granted from the UK Research Ethics Committee for the study. Information regarding governance/regulatory approvals for each international cohort are available in the Supp. Methods.

Keywords: COVID-19, cancer, SARS-CoV-2, decision support tool; CORONET

Suggested Citation

Lee, Rebecca and Wysocki, Oskar and Zhou, C. and Shotton, Rohan and Tivey, Ann and Lever, Louise and Woodcock, Joshua and Angelakas, Angelos and Arnold, D. and Aung, Theingi and Banfill, Kathryn and Baxter, Mark and Bhogal, Talvinder and Boyce, Hayley and Britton, Fiona and Calles, Antonio and Castelo-Branco, Louis and Copson, Ellen and Croitoru, Adina and Dani, Sourbha and Dickens, Elena and Eastlake, Leonie and Fitzpatrick, P. and Frost, H. and Ganatra, Sarju and Gennatas, Spyridon and Gomes, F. and Graham, Donna and Hague, Christina and Harrington, Kevin and Harrison, Michelle and Horsley, Laura and Hoskins, R. and Huddar, Prerana and Hudson, Zoe and Joharatnam-Hogan, Nalinie and Khan, S. and Khan, U.T. and Khan, Khurum and Maynard, Alec and McKenzie, H. and Michielin, Olivier and Mosenthal, Anne and Obispo, Berta and Patel, Rushin and pentheroudakis, George and peters, solange and Rieger-Christ, Kimberly and Robinson, T. and Rogado, Jacobo and Romano, Emanuela and Rowe, M. and Sekacheva, Marina and Sheehan, Roseleen and Stevenson, Julie and Stockdale, Alexander J. and Thomas, A. and Turtle, Lance and Viñal, D. and Weaver, J. and Williams, S. and Wilson, C. and Palmieri, Carlo and Landers, Donal and Cooksley, Tim and Group, ESMO Co-Care and Dive, Caroline and Freitas, Andre and Armstrong, A. C., Establishment of CORONET: COVID-19 Risk in Oncology Evaluation Tool to Identify Cancer Patients at Low Versus High Risk of Severe Complications of COVID-19 Infection Upon Presentation to Hospital. Available at SSRN: https://ssrn.com/abstract=3893474 or http://dx.doi.org/10.2139/ssrn.3893474

Rebecca Lee (Contact Author)

The Christie NHS Foundation Trust ( email )

Wilmslow Road
Manchester, M20 4BX
United Kingdom

Oskar Wysocki

University of Manchester

Booth St West
Manchester, N/A M15 6PB
United Kingdom

C. Zhou

University of Manchester - Digital Experimental Cancer Medicine

Oxford Road
Manchester, N/A M13 9PL
United Kingdom

Rohan Shotton

affiliation not provided to SSRN

No Address Available

Ann Tivey

affiliation not provided to SSRN

Louise Lever

University of Manchester

Joshua Woodcock

University of Manchester

Booth St West
Manchester, N/A M15 6PB
United Kingdom

Angelos Angelakas

affiliation not provided to SSRN

No Address Available

D. Arnold

ITG, Inc. - ITG London

Ropemaker Place
25 Ropemaker Street
London, EC2Y 9LY
United Kingdom

Theingi Aung

affiliation not provided to SSRN

No Address Available

Kathryn Banfill

affiliation not provided to SSRN

No Address Available

Mark Baxter

University of Dundee

Dundee, DD1 4HN
United Kingdom

Talvinder Bhogal

affiliation not provided to SSRN

No Address Available

Hayley Boyce

affiliation not provided to SSRN

No Address Available

Fiona Britton

affiliation not provided to SSRN

No Address Available

Antonio Calles

Hospital General Universitario Gregorio Marañón ( email )

C/Dr. Esquerdo, 46
Madrid, Madrid 28007
Spain

Louis Castelo-Branco

affiliation not provided to SSRN

No Address Available

Ellen Copson

University of Southampton - University Hospital Southampton NHS Foundation Trust

University Rd.
Southampton SO17 1BJ, SO17 1LP
United Kingdom

Adina Croitoru

Fundeni Clinical Institute ( email )

258
București
Romania

Sourbha Dani

affiliation not provided to SSRN

No Address Available

Elena Dickens

affiliation not provided to SSRN

No Address Available

Leonie Eastlake

University Hospitals Plymouth NHS Trust

Plymouth, PL6 8DH
United Kingdom

P. Fitzpatrick

University of Manchester - Digital Experimental Cancer Medicine

Oxford Road
Manchester, N/A M13 9PL
United Kingdom

H. Frost

University of Manchester - Digital Experimental Cancer Medicine

Oxford Road
Manchester, N/A M13 9PL
United Kingdom

Sarju Ganatra

affiliation not provided to SSRN

No Address Available

Spyridon Gennatas

affiliation not provided to SSRN

No Address Available

F. Gomes

The Christie NHS Foundation Trust

Wilmslow Road
Manchester, M20 4BX
United Kingdom

Donna Graham

affiliation not provided to SSRN

No Address Available

Christina Hague

affiliation not provided to SSRN

No Address Available

Kevin Harrington

NHS Foundation Trust - Royal Marsden Hospital

Sutton
Surrey
London
United Kingdom

Michelle Harrison

Ninewells Hospital and Medical School

Laura Horsley

affiliation not provided to SSRN

No Address Available

R. Hoskins

University of Manchester - Research IT

Oxford Road
Manchester, N/A M13 9PL
United Kingdom

Prerana Huddar

affiliation not provided to SSRN

No Address Available

Zoe Hudson

affiliation not provided to SSRN

No Address Available

Nalinie Joharatnam-Hogan

University College London Hospital ( email )

S. Khan

Government of the United Kingdom - Oncology Department

Groby Road
Leicester, LE3 9QP
United Kingdom

U.T. Khan

Clatterbridge Cancer Centre

Birkenhead
United Kingdom

Khurum Khan

University College London - UCL Cancer Institute ( email )

Gower Street
London, WC1E 6BT
United States

Alec Maynard

affiliation not provided to SSRN

No Address Available

H. McKenzie

University of Southampton - Cancer Sciences Academic Unit

University Rd.
Southampton SO17 1BJ, Hampshire SO17 1LP
United Kingdom

Olivier Michielin

affiliation not provided to SSRN

No Address Available

Anne Mosenthal

affiliation not provided to SSRN

No Address Available

Berta Obispo

affiliation not provided to SSRN

No Address Available

Rushin Patel

affiliation not provided to SSRN

No Address Available

George Pentheroudakis

affiliation not provided to SSRN

No Address Available

Solange Peters

affiliation not provided to SSRN

Kimberly Rieger-Christ

affiliation not provided to SSRN

No Address Available

T. Robinson

Bristol Haematology and Oncology Centre

Bristol
United Kingdom

Jacobo Rogado

affiliation not provided to SSRN

No Address Available

Emanuela Romano

affiliation not provided to SSRN

No Address Available

M. Rowe

Royal Cornwall Hospital - Sunrise Centre

Treliske
United Kingdom

Marina Sekacheva

I.M. Sechenov First Moscow State Medical University ( email )

Trubetskaya ul., 8
Moscow
Russia

Roseleen Sheehan

affiliation not provided to SSRN

No Address Available

Julie Stevenson

affiliation not provided to SSRN

No Address Available

Alexander J. Stockdale

National Institute for Health Research (NIHR) ( email )

London, Oxfordshire
United Kingdom

A. Thomas

Government of the United Kingdom - Oncology Department

Groby Road
Leicester, LE3 9QP
United Kingdom

Lance Turtle

University of Liverpool - NIHR Health Protection Research Unit in Emerging and Zoonotic Infections

D. Viñal

Hospital Universitario La Paz - Department of Medical Oncology

Madrid
Spain

J. Weaver

The Christie NHS Foundation Trust

Wilmslow Road
Manchester, M20 4BX
United Kingdom

S. Williams

Government of the United Kingdom - Weston Park Cancer Centre

Sheffield
United Kingdom

C. Wilson

Government of the United Kingdom - Weston Park Cancer Centre

Sheffield
United Kingdom

Carlo Palmieri

affiliation not provided to SSRN

No Address Available

Donal Landers

affiliation not provided to SSRN

No Address Available

Tim Cooksley

The Christie NHS Foundation Trust

Wilmslow Road
Manchester, M20 4BX
United Kingdom

ESMO Co-Care Group

Independent

Caroline Dive

University of Manchester

Oxford Road
Manchester, N/A M13 9PL
United Kingdom

Cancer Research UK Lung Cancer Centre of Excellence

United Kingdom

Andre Freitas

University of Manchester

Booth St West
Manchester, N/A M15 6PB
United Kingdom

A. C. Armstrong

The Christie NHS Foundation Trust

Wilmslow Road
Manchester, M20 4BX
United Kingdom

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