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      COVID-19 in patients with thoracic malignancies (TERAVOLT): first results of an international, registry-based, cohort study

      , MD a , * , , PhD c , , PhD d , , PhD b , , MD e , , MD f , , MD g , , MD h , , MD i , , MD j , , MD k , , MD l , , MD m , , MD a , , MD n , , MD o , , MD p , , MD q , , MD r , , MD s , , MD t , , MD u , , MD v , , MD w , , MD y , , MD z , , MD aa , , MD ab , , MD ac , , MD ad , , MD ae , , MD af , , MD ag , , MD ah , , MD ai , , MD aj , , MD ak , , MD al , , MD a , , MD ai , , MD am , , MD x , , PhD an , , MD ao , , Prof, MD ap , , Prof, MD aq , , MD ar , * , , MD ad , * , , MD as , * , TERAVOLT investigators
      The Lancet. Oncology
      Elsevier Ltd.

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          Early reports on patients with cancer and COVID-19 have suggested a high mortality rate compared with the general population. Patients with thoracic malignancies are thought to be particularly susceptible to COVID-19 given their older age, smoking habits, and pre-existing cardiopulmonary comorbidities, in addition to cancer treatments. We aimed to study the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on patients with thoracic malignancies.


          The Thoracic Cancers International COVID-19 Collaboration (TERAVOLT) registry is a multicentre observational study composed of a cross-sectional component and a longitudinal cohort component. Eligibility criteria were the presence of any thoracic cancer (non-small-cell lung cancer [NSCLC], small-cell lung cancer, mesothelioma, thymic epithelial tumours, and other pulmonary neuroendocrine neoplasms) and a COVID-19 diagnosis, either laboratory confirmed with RT-PCR, suspected with symptoms and contacts, or radiologically suspected cases with lung imaging features consistent with COVID-19 pneumonia and symptoms. Patients of any age, sex, histology, or stage were considered eligible, including those in active treatment and clinical follow-up. Clinical data were extracted from medical records of consecutive patients from Jan 1, 2020, and will be collected until the end of pandemic declared by WHO. Data on demographics, oncological history and comorbidities, COVID-19 diagnosis, and course of illness and clinical outcomes were collected. Associations between demographic or clinical characteristics and outcomes were measured with odds ratios (ORs) with 95% CIs using univariable and multivariable logistic regression, with sex, age, smoking status, hypertension, and chronic obstructive pulmonary disease included in multivariable analysis. This is a preliminary analysis of the first 200 patients. The registry continues to accept new sites and patient data.


          Between March 26 and April 12, 2020, 200 patients with COVID-19 and thoracic cancers from eight countries were identified and included in the TERAVOLT registry; median age was 68·0 years (61·8–75·0) and the majority had an Eastern Cooperative Oncology Group performance status of 0–1 (142 [72%] of 196 patients), were current or former smokers (159 [81%] of 196), had non-small-cell lung cancer (151 [76%] of 200), and were on therapy at the time of COVID-19 diagnosis (147 [74%] of 199), with 112 (57%) of 197 on first-line treatment. 152 (76%) patients were hospitalised and 66 (33%) died. 13 (10%) of 134 patients who met criteria for ICU admission were admitted to ICU; the remaining 121 were hospitalised, but were not admitted to ICU. Univariable analyses revealed that being older than 65 years (OR 1·88, 95% 1·00–3·62), being a current or former smoker (4·24, 1·70–12·95), receiving treatment with chemotherapy alone (2·54, 1·09–6·11), and the presence of any comorbidities (2·65, 1·09–7·46) were associated with increased risk of death. However, in multivariable analysis, only smoking history (OR 3·18, 95% CI 1·11–9·06) was associated with increased risk of death.


          With an ongoing global pandemic of COVID-19, our data suggest high mortality and low admission to intensive care in patients with thoracic cancer. Whether mortality could be reduced with treatment in intensive care remains to be determined. With improved cancer therapeutic options, access to intensive care should be discussed in a multidisciplinary setting based on cancer specific mortality and patients' preference.



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          Most cited references22

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Clinical Characteristics of Coronavirus Disease 2019 in China

            Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
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              Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

              Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

                Author and article information

                Lancet Oncol
                Lancet Oncol
                The Lancet. Oncology
                Elsevier Ltd.
                12 June 2020
                12 June 2020
                [a ]Thoracic Unit, Medical Oncology Department, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
                [b ]Evaluative Epidemiology, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
                [c ]Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
                [d ]Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
                [e ]Laboratory of Clinical Research Methodology, Oncology Department, “Mario Negri” Institute of Pharmacological Researches-IRCCS, Milan, Italy
                [f ]Medical Oncology Department, Fondazione IRCCS Policlinico “San Matteo”, Pavia, Italy
                [g ]Medical Oncology Department, Thoracic Cancer and Early Drug Development Unit, Hospital Universitario 12 de Octubre, Madrid, Spain
                [h ]Department of Oncology, Portsmouth Hospitals NHS Trust, Portsmouth, UK
                [i ]Medical Oncology Department, AOU Ospedali Riuniti di Ancona, Università Politecnica delle Marche, Ancona, Italy
                [j ]Oncology Unit, ASST Papa Giovanni XXIII, Bergamo, Italy
                [k ]Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
                [l ]Medical Oncology Department, ASST Cremona, Cremona, Italy
                [m ]Hopital Tenon, Paris, France
                [n ]Oncology Unit, ASST dei Sette Laghi, Varese, Italy
                [o ]Department of Biotechnology and Applied Clinical Science, University of L'Aquila, L'Aquila, Italy
                [p ]Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, Spain
                [q ]Humanitas Clinical and Research Center IRCCS, Rozzano, Italy
                [r ]IRYCIS, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Madrid, Spain
                [s ]IRCCS Ospedale Policlinico San Martino, Genova, Italy
                [t ]Medical Oncology Unit, Sant'Andrea Hospital, Rome, Italy
                [u ]Department of Oncology, IRCCS Ospedale San Raffaele, Milan, Italy
                [v ]Medical Oncology Department, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
                [w ]Mesothelioma Unit, Azienda Ospedaliera Nazionale Santi Antonio e Biagio e Cesare Arrigo, Alessandria, Italy
                [x ]Medical Oncology Department, Azienda Ospedaliera Nazionale Santi Antonio e Biagio e Cesare Arrigo, Alessandria, Italy
                [y ]Medical Oncology Department, ASST Spedali Civili di Brescia, Brescia, Italy
                [z ]Medical Oncology Department, ASST Fatebenefratelli Sacco, Milan, Italy
                [aa ]Georgetown Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC
                [ab ]CHU, Institut universitaire du cancer, Toulouse, France
                [ac ]Thoracic Surgery Unit, Experimental Clinical Oncology Department, IRCCS Regina Elena National Cancer Institute, Rome, Italy
                [ad ]Oncology Department, Lausanne University Hospital, Lausanne University, Lausanne, Switzerland
                [ae ]Department of Oncology and Hematology, AUSL della Romagna, Ravenna, Italy
                [af ]Service Hospitalier Universitaire Pneumologie Physiologie, CHU Grenoble-Alpes, Grenoble, France
                [ag ]Istituto Oncologico Veneto IRCCS, Padova, Italy
                [ah ]European Institute of Oncology, European Institute of Oncology IRCCS, Milan, Italy
                [ai ]Radiotherapy Unit V Scotti, Thoracic Surgery Unit L Voltolini, Azienda Ospedaliero Universitaria Careggi, Firenze, Italy
                [aj ]Thoracic Surgery, Policlinico S Orsola, Alma Mater Studiorum University, Bologna, Italy
                [ak ]Medical Oncology Unit, Ospedale “Guglielmo da Saliceto”, Piacenza, Italy
                [al ]Department of Medicine and Surgery, University of Parma, University Hospital of Parma, Parma, Italy
                [am ]Guangdong Lung Cancer Department, Guangdong General Hospital, Guangzhou, China
                [an ]Centre de Recherche en Cancérologie de Toulouse, Toulouse, France
                [ao ]Department of Pulmonology, Erasmus University Medical Center, Rotterdam, University Maastricht, Maastricht, Netherlands
                [ap ]Department of Pulmonology and Thoracic Oncology, Antwerp University Hospital, Edegem, Belgium
                [aq ]Gustave Roussy Institute, Villejuif, Aix Marseille University, CNRS, INSERM, CRCM, Marseille, France
                [ar ]Stanford Cancer Institute, Stanford University, Stanford, CA, USA
                [as ]Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA
                Author notes
                [* ]Correspondence to: Dr Marina Chiara Garassino, Thoracic Oncology Unit, Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, 20126 Milan, Italy marina.garassino@ 123456istitutotumori.mi.it

                Contributed equally


                Members are listed in the appendix (pp 8–11)

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                Oncology & Radiotherapy
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