Determinants of the outcomes of patients with cancer infected with SARS-CoV-2: results from the Gustave Roussy cohort

Articles https://doi.org/10.1038/s43018-020-00120-5 Determinants of the outcomes of patients with cancer infected with SARS-CoV-2: results from the Gustave Roussy cohort Laurence Albiges1, Stéphanie Foulon2, Arnaud Bayle1, Bertrand Gachot3, Fanny Pommeret1,3, Christophe Willekens4, Annabelle Stoclin3, Mansouria Merad3, Frank Griscelli5, Ludovic Lacroix5, Florence Netzer6, Thomas Hueso4, Corinne Balleyguier7, Samy Ammari7, Emeline Colomba1, Giulia Baciarello1, Audrey Perret1, Antoine Hollebecque1,8, Julien Hadoux7, Jean-Marie Michot8, Nathalie Chaput 4, Veronique Saada5, Mathilde Hauchecorne1, Jean-Baptiste Micol 4, Roger Sun 9, Dominique Valteau-Couanet10, Fabrice André 1, Florian Scotte3, Benjamin Besse1, Jean-Charles Soria11 and Fabrice Barlesi 11,12 ✉ Patients with cancer are presumed to be at increased risk of severe COVID-19 outcomes due to underlying malignancy and treatment-induced immunosuppression. Of the first 178 patients managed for COVID-19 at the Gustave Roussy Cancer Centre, 125 (70.2%) were hospitalized, 47 (26.4%) developed clinical worsening and 31 (17.4%) died. An age of over 70 years, smoking status, metastatic disease, cytotoxic chemotherapy and an Eastern Cooperative Oncology Group score of ≥2 at the last visit were the strongest determinants of increased risk of death. In multivariable analysis, the Eastern Cooperative Oncology Group score remained the only predictor of death. In contrast, immunotherapy, hormone therapy and targeted therapy did not increase clinical worsening or death risk. Biomarker studies found that C-reactive protein and lactate dehydrogenase levels were significantly associated with an increased risk of clinical worsening, while C-reactive protein and D-dimer levels were associated with an increased risk of death. COVID-19 management impacted the oncological treatment strategy, inducing a median 20 d delay in 41% of patients and adaptation of the therapeutic strategy in 30% of patients. B y early March 2020, the spread of the coronavirus disease 2019 (COVID-19) outbreak had reached the Paris area, France. Since then, all medical resources have been reorganized to handle the pandemic. As a tertiary cancer center, Gustave Roussy has followed two objectives: define processes to safely sustain cancer care in a secured environment and reorganize internally to adapt its capacities to hospitalize patients with cancer and COVID-19 illness. Patients with cancer have been considered at increased risk of COVID-19, on the rationale of the increased systemic immunosuppressive state caused by the underlying malignancy and anticancer treatments. The first report from a retrospective cohort in China suggested that patients with cancer were observed to have a higher risk of severe events (for example, a composite endpoint of intensive care unit (ICU) admission, invasive ventilation or death) compared with patients without cancer (seven (39%) of 18 patients versus 124 (8%) of 1,572 patients; P = 0.0003) and that patients with cancer deteriorated more rapidly than those without cancer1. While general determinants of COVID-19 severity have emerged from large cohorts from China and Italy2,3, limited data are available on the specificity of patients with cancer to help the oncology community to identify patients at risk of severe COVID-19. Furthermore, the impact of COVID-19 infection on ongoing cancer care is unexplored. This study investigated the determinants of clinical worsening and death, as well as the impact on cancer care, for the first patients sequentially managed for COVID-19 and cancer in an academic tertiary cancer center. Results Patient population. From 24 March 2020 until 29 April 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected in 196 (12%) of 1,633 tests performed internally at the Gustave Roussy Cancer Centre. Overall, 209 patients were identified (including a few identified by PCR with reverse transcription (RT-PCR) performed at another facility and some diagnosed by computed tomography scan alone) and the final study population included 178 adult patients. The following were reasons for exclusion: pediatric population (six patients); non-cancer patients (19 patients); and COVID-19 ultimately ruled out (six patients). Baseline demographics, comorbidities and underlying cancer characteristics for Cancer Medicine Department, Gustave Roussy, Paris-Saclay University, Paris, France. 2Biostatistics Department, Gustave Roussy, Paris-Saclay University, Paris, France. 3Interdisciplinary Cancer Course Department, Gustave Roussy, Paris-Saclay University, Paris, France. 4Haematology Department, Gustave Roussy, Paris-Saclay University, Paris, France. 5Biopathology Department, Gustave Roussy, Paris-Saclay University, Paris, France. 6Pharmacy Department, Gustave Roussy, Paris-Saclay University, Paris, France. 7Imaging Department, Gustave Roussy, Paris-Saclay University, Paris, France. 8 Early Drug Development Department, Gustave Roussy, Paris-Saclay University, Paris, France. 9Radiation Oncology Department, Gustave Roussy, Paris-Saclay University, Paris, France. 10Paediatric Oncology Department, Gustave Roussy, Paris-Saclay University, Paris, France. 11Gustave Roussy, Paris-Saclay University, Paris, France. 12Aix Marseille University, CNRS, INSERM, CRCM, Marseille, France. ✉e-mail: 1 Nature Cancer | VOL 1 | October 2020 | 965–975 | www.nature.com/natcancer 965 Articles Nature Cancer Table 1 | Patient characteristics (Continued) Table 1 | Patient characteristics Characteristic n (out of 178) Percentage Characteristic n (out of 178) Percentage Systemic treatments in the past 3 months Gender Male 76 42.7% Female 102 57.3% Yes 117 66.9% Cytotoxic chemotherapy 66 37.1% Age (years) Target therapy 30 16.9% Median (Q1–Q3) 61.0 (52.0–71.0) Hormone therapy 16 10.3% Mean (s.d.) 60.6 (14.8) Immune checkpoint inhibitor 19 10.7% ≥70 years old 50 28.1% Two patients with a solid tumor had a history of hematological malignancy and six patients with a hematological malignancy had a history of solid tumor. ACUP, adenocarcinoma of unknown primary; CNS, central nervous system; PS, performance status; Q1, first quartile; Q3, third quartile. a Smoking Never 89 50.6% Former 43 24.4% Current 20 11.4% Unknown 24 13.6% Comorbidities Hypertension 65 36.5% Diabetes 35 19.7% Dyslipidemia 16 9.0% Cardiac disease (ischemic/other) 9/21 5.1%/11.8% Chronic kidney disease 10 5.6% Autoimmune disease 9 5.1% BMI Median (Q1–Q3) 25.0 (22.0–28.0) Mean (s.d.) 25.0 (4.9) <18.5 12 7.4% 18.5–25 64 39.3% 25–30 62 38.0% ≥30 25 15.3% Diagnosis. The vast majority of patients (n = 138; 79.8%) presented with COVID-19 symptoms before any test or imaging. COVID-19 was suspected following symptoms prompting RT-PCR testing in 134 patients (75.7%) and following incidental findings on a computed tomography scan in 16 patients (9%), and was related to systematic screeni (...truncated)