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Prevalence and impact of COVID-19 sequelae on treatment and survival of patients with cancer who recovered from SARS-CoV-2 infection: evidence from the OnCovid retrospective, multicentre registry study - 30/11/21

Doi : 10.1016/S1470-2045(21)00573-8 
David J Pinato, PhD a, b, , Josep Tabernero, ProfPhD g, Mark Bower, ProfPhD j, k, Lorenza Scotti, PhD e, Meera Patel, BSc a, Emeline Colomba, MD l, Saoirse Dolly, PhD m, Angela Loizidou, MD n, John Chester, ProfPhD o, p, Uma Mukherjee, PhD q, Alberto Zambelli, MD r, Alessia Dalla Pria, MD j, k, Juan Aguilar-Company, MD g, Diego Ottaviani, PhD s, Amani Chowdhury, MD s, Eve Merry, MD s, Ramon Salazar, PhD t, Alexia Bertuzzi, MD v, Joan Brunet, PhD w, Matteo Lambertini, PhD x, y, Marco Tagliamento, MD x, y, Anna Pous, MD w, Ailsa Sita-Lumsden, PhD m, Krishnie Srikandarajah, MBBS m, Johann Colomba, MD l, Fanny Pommeret, MD l, Elia Seguí, MD z, Daniele Generali, ProfPhD ab, ac, Salvatore Grisanti, PhD ad, ae, Paolo Pedrazzoli, ProfMD af, Gianpiero Rizzo, MD ae, Michela Libertini, MD ag, Charlotte Moss, MRes ah, Joanne S Evans, MPhil a, Beth Russell, PhD ah, Nadia Harbeck, ProfPhD ai, Bruno Vincenzi, PhD aj, Federica Biello, MD b, f, Rossella Bertulli, MD ak, Raquel Liñan, MD w, Sabrina Rossi, MD v, Maria Carmen Carmona-García, MD w, Carlo Tondini, MD r, Laura Fox, MD h, Alice Baggi, MD ad, ae, Vittoria Fotia, MD r, Alessandro Parisi, MD al, Giampero Porzio, MD am, Maristella Saponara, MD an, Claudia Andrea Cruz, MD z, David García-Illescas, MD g, Eudald Felip, MD w, Ariadna Roqué Lloveras, MD w, Rachel Sharkey, RN j, k, Elisa Roldán, MD g, Roxana Reyes, MD z, Irina Earnshaw, MBCHB s, Daniela Ferrante, PhD e, Javier Marco-Hernández, MD aa, Isabel Ruiz-Camps, PhD i, Gianluca Gaidano, MD d, f, Andrea Patriarca, MD d, f, Riccardo Bruna, MD d, f, Anna Sureda, PhD u, Clara Martinez-Vila, MD ao, Ana Sanchez de Torre, MD ap, Luca Cantini, MD aq, Marco Filetti, MD ar, Lorenza Rimassa, MD v, as, Lorenzo Chiudinelli, MD r, Michela Franchi, MD r, Marco Krengli, MD c, f, Armando Santoro, ProfMD v, as, Aleix Prat, ProfPhD z, at, Mieke Van Hemelrijck, ProfPhD ah, Nikolaos Diamantis, PhD q, Thomas Newsom-Davis, PhD j, k, Alessandra Gennari, PhD b, f, Alessio Cortellini, MD a, am
on behalf of the

OnCovid study group

  Members are listed in the Supplementary Material
Judith Swallow, Chris Chung, Gino Dettorre, Neha Chopra, Alvin JX Lee, Christopher CT Sng, Yien Ning Sophia Wong, Myria Galazi, Sarah Benafif, Palma Dileo, Grisma Patel, Anjui Wu, Alasdair Sinclair, Gehan Soosaipillai, Eleanor Jones, Nikolaos Diamantis, Uma Mukherjee, Amanda Jackson, Martine Piccart, Fanny Pommeret, Johann Colomba, Emeline Colomba-Blameble, Aleix Prat, Claudia A Cruz, Roxana Reyes, Elia Segui, Javier Marco-Hernández, Josep Tabernero, Juan Aguilar-Company, Isabel Ruiz-Camps, Laura Fox, David Garcia Illescas, Oriol Mirallas, Elisa Roldán, Anna Carbó, Isabel Garcia, Rachel Wuerstlein, Ricard Mesia, Clara Maluquer, Francesca D’Avanzo, Giuseppe Tonini, Salvatore Provenzano, Valeria Tovazzi, Corrado Ficorella, Paola Queirolo, Raffaele Giusti, Francesca Mazzoni, Federica Zoratto, Marco Tucci, Rossana Berardi, Annalisa Guida, Sergio Bracarda, Maria Iglesias

a Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK 
b Division of Oncology, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy 
c Division of Radiotherapy, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy 
d Division of Haematology, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy 
e Unit of Medical Statistics, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy 
f Azienda Ospedaliera Maggiore Della Caritá, Novara, Italy 
g Medical Oncology, Vall d’Hebron University Hospital and Institute of Oncology, Barcelona, Spain 
h Haematology, Vall d’Hebron University Hospital and Institute of Oncology, Barcelona, Spain 
i Infectious Diseases, Vall d’Hebron University Hospital and Institute of Oncology, Barcelona, Spain 
j Department of Oncology, Chelsea and Westminster Hospital, London, UK 
k National Centre for HIV Malignancy, Chelsea and Westminster Hospital, London, UK 
l Department of Cancer Medicine, Institut Gustave Roussy, University of Paris Saclay, Villejuif, France 
m Medical Oncology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK 
n Department of Infectious Diseases, Internal Medicine, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium 
o Medical Oncology, School of Medicine, Cardiff University, Cardiff, UK 
p Medical Oncology, Velindre Cancer Centre, Cardiff, UK 
q Medical Oncology, Barts Health NHS Trust, London, UK 
r Oncology Unit, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy 
s Cancer Division, University College London Hospitals, London, UK 
t Department of Medical Oncology, ICO L’Hospitalet, Oncobell Program, Hospitalet de Llobregat, Barcelona, Spain 
u Haematology Department, ICO L’Hospitalet, Oncobell Program, Hospitalet de Llobregat, Barcelona, Spain 
v Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy 
w Department of Medical Oncology, Catalan Institute of Oncology, University Hospital Josep Trueta, Girona, Spain 
x Medical Oncology Department, IRCCS Ospedale Policlinico San Martino, Genova, Italy 
y Department of Internal Medicine and Medical Specialties, School of Medicine, University of Genova, Genova, Italy 
z Department of Medical Oncology, Hospital Clinic, Barcelona, Spain 
aa Department of Internal Medicine, Hospital Clinic, Barcelona, Spain 
ab Multidisciplinary Breast Pathology and Translational Research Unit, Azienda Socio Sanitaria Territoriale Cremona, Cremona, Italy 
ac Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy 
ad Medical Oncology Unit, Spedali Civili, Brescia, Italy 
ae Medical Oncology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy 
af Department of Internal Medicine and Medical Therapy, University of Pavia, Pavia, Italy 
ag Medical Oncology Unit, Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy 
ah Translational Oncology and Urology Research, School of Cancer and Pharmaceutical Sciences, King’s College London, London, UK 
ai Department of Gynecology and Obstetrics, Breast Center and Gynecological Cancer Center and Comprehensive Cancer Center Munich, University Hospital Munich, Munich, Germany 
aj Policlinico Universitario Campus Bio-Medico, Rome, Italy 
ak Medical Oncology 2, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy 
al Department of Life, Health & Environmental Sciences, University of L’Aquila, L’Aquila, Italy 
am Department of Biotechnology and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy 
an Melanoma and Sarcoma Medical Treatment Unit, Istituto Europeo di Oncologia, Milan, Italy 
ao Fundació Althaia Manresa, Manresa, Spain 
ap Hospital Universitario XII de Octubre, Madrid, Spain 
aq Medical Oncology, Azienda Ospedaliero Universitaria, Ospedali Riuniti, Polytechnic University of the Marche Region, Ancona, Italy 
ar Medical Oncology, Sant’Andrea Hospital, Rome, Italy 
as Department of Biomedical Sciences, Humanitas University, Milan, Italy 
at Translational Genomics and Targeted Therapies in Solid Tumors, IDIBAPS, Barcelona, Spain, Barcelona, Spain 

* Correspondence to: Dr David J Pinato, Department of Surgery and Cancer, Imperial College London, Hammersmith hospital, London W12 0HS, UK Department of Surgery and Cancer Imperial College London Hammersmith hospital London W12 0HS UK

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Summary

Background

The medium-term and long-term impact of COVID-19 in patients with cancer is not yet known. In this study, we aimed to describe the prevalence of COVID-19 sequelae and their impact on the survival of patients with cancer. We also aimed to describe patterns of resumption and modifications of systemic anti-cancer therapy following recovery from SARS-CoV-2 infection.

Methods

OnCovid is an active European registry study enrolling consecutive patients aged 18 years or older with a history of solid or haematological malignancy and who had a diagnosis of RT-PCR confirmed SARS-CoV-2 infection. For this retrospective study, patients were enrolled from 35 institutions across Belgium, France, Germany, Italy, Spain, and the UK. Patients who were diagnosed with SARS-CoV-2 infection between Feb 27, 2020, and Feb 14, 2021, and entered into the registry at the point of data lock (March 1, 2021), were eligible for analysis. The present analysis was focused on COVID-19 survivors who underwent clinical reassessment at each participating institution. We documented prevalence of COVID-19 sequelae and described factors associated with their development and their association with post-COVID-19 survival, which was defined as the interval from post-COVID-19 reassessment to the patients’ death or last follow-up. We also evaluated resumption of systemic anti-cancer therapy in patients treated within 4 weeks of COVID-19 diagnosis. The OnCovid study is registered in ClinicalTrials.gov, NCT04393974.

Findings

2795 patients diagnosed with SARS-CoV-2 infection between Feb 27, 2020, and Feb 14, 2021, were entered into the study by the time of the data lock on March 1, 2021. After the exclusion of ineligible patients, the final study population consisted of 2634 patients. 1557 COVID-19 survivors underwent a formal clinical reassessment after a median of 22·1 months (IQR 8·4–57·8) from cancer diagnosis and 44 days (28–329) from COVID-19 diagnosis. 234 (15·0%) patients reported COVID-19 sequelae, including respiratory symptoms (116 [49·6%]) and residual fatigue (96 [41·0%]). Sequelae were more common in men (vs women; p=0·041), patients aged 65 years or older (vs other age groups; p=0·048), patients with two or more comorbidities (vs one or none; p=0·0006), and patients with a history of smoking (vs no smoking history; p=0·0004). Sequelae were associated with hospitalisation for COVID-19 (p<0·0001), complicated COVID-19 (p<0·0001), and COVID-19 therapy (p=0·0002). With a median post-COVID-19 follow-up of 128 days (95% CI 113–148), COVID-19 sequelae were associated with an increased risk of death (hazard ratio [HR] 1·80 [95% CI 1·18–2·75]) after adjusting for time to post-COVID-19 reassessment, sex, age, comorbidity burden, tumour characteristics, anticancer therapy, and COVID-19 severity. Among 466 patients on systemic anti-cancer therapy, 70 (15·0%) permanently discontinued therapy, and 178 (38·2%) resumed treatment with a dose or regimen adjustment. Permanent treatment discontinuations were independently associated with an increased risk of death (HR 3·53 [95% CI 1·45–8·59]), but dose or regimen adjustments were not (0·84 [0·35–2·02]).

Interpretation

Sequelae post-COVID-19 affect up to 15% of patients with cancer and adversely affect survival and oncological outcomes after recovery. Adjustments to systemic anti-cancer therapy can be safely pursued in treatment-eligible patients.

Funding

National Institute for Health Research Imperial Biomedical Research Centre and the Cancer Treatment and Research Trust.

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Vol 22 - N° 12

P. 1669-1680 - décembre 2021 Retour au numéro
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