ABSTRACT
Declaration de liens d'interets: Les auteurs declarent ne pas avoir de liens d'interets. Copyright © 2022
ABSTRACT
Background: Each decade since 2000, the French College of General Hospital Pulmonologists (CPHG) conducts a real-life nationwide prospective epidemiological, observational, multicenter study on lung cancer (LC). In 2020, the CPHG constituted the third cohort, KBP-2020-CPHG. We reported here the data on one-month and three-month mortality among general population of this cohort and compared them with 2010 cohort. Methods: Collection of all consecutive LC histologically or cytologically confirmed between 01/01 and 12/31/2020 in non-academic public hospital pulmonology or oncology units in France. A Scientific Committee controlled inclusion exhaustivity and quality in each center. Results: 82 centers collected 8,999 patients in 2020. One-month mortality was 8.8% (734/8,999) and 9.7% (680/7,051) in 2010. Three-month mortality was 21.5% (1,771/8,999) in 2020 and 23.3% (1,624/7,051) in 2010 (Table 1). According to sex, mortality at one and three months mainly affected men (525/734;71.5% and 1,259/1,771;71.1% respectively). Mean age at diagnosis was older than in the cohort population (67.8 y-o);respectively 69.9 and 69.8 at one and three months. At diagnosis, patients were in poorer ECOG mainly grade 2 (211/697;30.3%) or 3 (194/697;27.8%) for one-month and mainly grade 1 (549/1,703;32.2%) or 2 (547/1,703;32.1%) for three-month mortality. Among ECOG grade 3 and 4, 34.8% (194/557) and 57.1% (93/163) were dead at one month respectively;63.5% (350/551) and 83.4% (136/163) respectively were dead at three months. According to histology, adenocarcinoma was the most common (308/734;42%), followed by small cell lung cancer (170/734;23.2%) at one-month;adenocarcinoma was also the most common (822/ 1,771;46.4%), followed by squamous cell carcinoma (380/1771;21.5%) at three-month mortality. Most patients who died early were stage 4, metastatic/disseminated (respectively 625/702;89% and 1,488/1,715;86.8% for one- and three-month mortality). In patients with COVID19 infection (n=547), mortality at one and three months was respectively 36.4% (174/478) and 46.7% (228/ 488). Conclusions: Early mortality has not improved over the two decades and remains high. KBP- 2020-CPHG study was performed during COVID-19 pandemic, which may have generated delays in diagnosis and limited access to care and hospital. Early mortality at one and three months concerned mostly men, mean age nearly 70 y-o, adenocarcinoma, metastatic disease and frail patients. This confirms the potential value of LC screening program in a targeted population.
ABSTRACT
BACKGROUND AND AIMS: Initial WHO guidance advised cautious fluid administration for patients with COVID-19 due to concern about the development of acute respiratory distress syndrome (ARDS). However, as the pandemic unfolded it became apparent that patients who were admitted to hospital had high rates of AKI and this initiated a change in local clinical guidelines during early April 2020. We aimed to ascertain the impact of judicious intravenous fluid use on mortality, length of hospitalisation and AKI. METHOD: An observational cohort study of 158 adults admitted with confirmed SARS-Cov-2 between 18th March and 9th May 2020 was conducted in a teaching hospital and designated centre for infectious diseases, London, UK. Key clinical and demographic data collected included clinical severity markers on admission, biochemical and haematological parameters as well as radiological findings. Primary outcomes were inpatient mortality, mortality at 6-weeks post discharge, length of hospitalisation and intensive care (ICU) admission. We also measured requirement for kidney replacement therapy (KRT) and AKI recovery rate at discharge. Using tests of difference, we compared key outcomes between patients treated with varying fluid regimens and then identified risk factors for AKI and mortality using multivariate logistic regression with results expressed as odds ratios (OR) with corresponding 95% confidence interval (CI). RESULTS: The median age was 74.4 (IQR 59.90 - 84.35) years, 66% were male, 53% white with hypertension and diabetes being the commonest co-morbidities. The median duration of illness prior to admission was 7 days (IQR 2 - 10) with respiratory symptoms and fever most prevalent. The people who presented with AKI on admission were more likely to receive fluids (34% vs 15%, p=0.02). 118 patients (75%) received fluids within 24-hours of admission with no difference in volume administered after local guidance change (p=0.78). Comparing patients receiving fluids with those who did not, we observed no difference in mortality (p=0.97), duration of hospital stays (p=0.26) or requirement for ICU admission (p=0.70). 18% died as an inpatient, and 52 patients were either admitted with or developed AKI. Of these 52 patients, 43 received fluids and 9 did not with no difference in KRT requirement (p=0.34), mortality (p=0.50) or AKI recovery (p=0.63). Peak AKI stage was greater among participants who received fluids though stage of AKI at presentation was also greater (p=0.04). Mortality rate in patients with an AKI is higher compared to overall inpatient mortality (31% vs 18%). Of the 36 patients with AKI (Figure Presnted) who were discharged home, 25 patients (69.4%) had renal recovery by the time of discharge. Increasing age and clinical severity on admission were associated with higher mortality (see Figure 1). Older age was associated with 34 - 53 times higher risk of death compared with those aged ≥ 65 years (age 76 - 85 years: OR 34.26, 95% CI: 3.94 - 297.48, p=0.001;age > 85 years: OR 53.07, 95% CI: 5.23 - 539.03, p=0.001). Patients with NEWS2 >4 on admission has 5-fold increased risk of death than those with a score ≥4 (OR 5.26, 95% CI: 1.32 - 20.92). Black ethnicity was associated with a 16-fold increased risk of developing AKI (OR 15.86, 95% CI: 1.67 - 150.99). CONCLUSION: To our knowledge, this is the first study to examine the impact of fluid management on inpatient mortality as well as on renal-associated outcomes of COVID-19 admission. Fluid administration regimen did not have an impact on mortality, length of hospitalisation or ICU admission, nor did it affect renal outcomes. Given the high rates of AKI and KRT in COVID-19 disease, early fluid administration is likely to be an important cornerstone of future management. Further adequately powered prospective studies are required to identify whether early fluid administration can reduce renal injury.
ABSTRACT
Background: Frailty is a known predictor of mortality and poor outcomes during hospital admission. In this large renal retrospective cohort study, we investigated whether frailer COVID-19 positive renal patients had worse outcomes. Design: All SARS-Cov-2 positive renal patients aged >=18 years who presented to the emergency department at the Royal Free Hospital or at the satellite dialysis centres from 10th of March until the 10th of May 2020, with recent data on frailty, were included. The follow up was until 26th of May 2020. Age, gender, ethnicity, body mass index, chronic kidney disease stage, modality of renal replacement therapy, co-morbidities, Rockwood clinical frailty score (CFS), C reactive protein and the neutrophil-to-lymphocyte count were collected at presentation. The primary outcome was the overall mortality rate following COVID-19 diagnosis. Secondary outcomes included the need for hospital admission.
ABSTRACT
Background: Tedopi® is an anticancer vaccine with modified neoepitopes restricted to HLA-A2+ targeting five tumor-associated antigens frequently expressed in lung cancer: CEA, HER2, MAGE2, MAGE3 and P53. ATALANTE-1 was a randomized, open-label, 2-Step phase 3 study comparing the efficacy of Tedopi® with standard treatment (SoC) in HLA-A2+ NSCLC patients in 2nd or 3rd line treatment after progression on ICI. Methods: HLA-A2+ NSCLC patients, EGFR and ALK negative, having progressed to platinum-based chemotherapy (CT) and anti-PD(L)1, ECOG PS 0-1 were randomized 2:1 to receive Tedopi® subcutaneously Q3W for 6 cycles, followed by maintenance Q8W up to first year, then Q12W, or SoC (docetaxel 75 mg/m2 Q3W or pemetrexed 500 mg/m2 Q3W). The Step-1 hypotheses were based on the evaluation of 1y-OS rate (Fleming design: H0 futility boundary at 25%;H1 alternative efficacy: 40% of OS rate at 12 months). Step-2 was a superiority study with OS as primary endpoint. Results: At cutoff of February 2020, 99 patients (Tedopi® n=63;SoC n=36) were randomized and analyzable for Step-1. The 1y-OS was 29/63 (46%) [95%CI 33-59]) in Tedopi® group and 13/36 (36%) [95%CI 21-54] in SoC. The Step-1 endpoint has shown a lower limit of the 95% confidence interval above the futility boundary (25%) with an OS estimate of 10% above the estimate of SoC. Secondary endpoints and subgroup data will be further presented. Grade 3-4 related TEAEs were 11 % in Tedopi® group and 43 % in SoC. There was no related grade 5 TEAE. Related TEAE leading to withdrawal from the study were also less frequent in Tedopi® group (6%) versus SoC (14%). Due to the risk of COVID-19 pandemic on data integrity, following recommendation of the Independent Data Monitoring Committee and Steering Committee, the decision was taken to early terminate the study at Step-1 and definitely stop new accrual while continuing the OS follow-up in all patients. Conclusions: The Step-1 primary endpoint was positively achieved with a 1y-OS rate of 46% and a good safety profile. Step-1 results shown a favorable benefit/risk of Tedopi® over SoC as 2nd or 3rd line treatment in advanced HLA-A2+ NSCLC patients after failure to ICI. Clinical trial identification: EudraCT: 2015-003183-36;NCT02654587. Legal entity responsible for the study: OSE Immunotherapeutics. Funding: OSE Immunotherapeutics. Disclosure: G. Giaccone: Advisory/Consultancy: CStone;Advisory/Consultancy: Novartis;Advisory/Consultancy: Daiichi;Research grant/Funding (institution): Medimunne;Research grant/Funding (institution): Incyte. E. Felip: Advisory/Consultancy: AbbVie;Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca;Advisory/Consultancy: Blueprint Medicine;Advisory/Consultancy, Speaker Bureau/Expert testimony: Boehringer Ingelheim;Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS;Advisory/Consultancy, Speaker Bureau/Expert testimony: Elli Lilly;Advisory/Consultancy: Guardant Health;Advisory/Consultancy: Janssen;Advisory/Consultancy: Merck KgaA;Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD;Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis;Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer;Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche;Advisory/Consultancy: Samsung;Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda;Advisory/Consultancy: GSK;Advisory/Consultancy: Bayer;Speaker Bureau/Expert testimony: Medscape;Speaker Bureau/Expert testimony: Prime Oncology;Speaker Bureau/Expert testimony: Touchime;Research grant/Funding (institution): Fundation Merck Salud;Advisory/Consultancy: Grifols. R. Garcia Campelo: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca;H noraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD. F. DENIS: Advisory/Consultancy, Travel/Accommodation/Expenses: Roche;Advisory/Consultancy: Shugai;Advisory/Consultancy: AstraZeneca;Advisory/Consultancy: Bayer;Advisory/Consultancy: MSD;Advisory/Consultancy, Licensing/Royalties: Sivan. E. Quoix: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS;Speaker Bureau/Expert testimony: Shugai;Travel/Accommodation/Expenses: Roche;Travel/Accommodation/Expenses: Takeda;Honoraria (self), interview at ASCO 2019: Medscape. A. Madroszyk: Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca;Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche;Travel/Accommodation/Expenses: Pfizer;Travel/Accommodation/Expenses: MSD. D. Debieuvre: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): MSD;Honoraria (self), Research grant/Funding (institution): AstraZeneca;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche;Honoraria (self): Shugai;Advisory/Consultancy, Research grant/Funding (institution): Pfizer;Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis;Research grant/Funding (institution): Lilly;Research grant/Funding (institution): Sandoz;Travel/Accommodation/Expenses: Boehringer Ingelheim. W. Hilgers: Advisory/Consultancy, Travel/Accommodation/Expenses: BMS;Honoraria (self): MSD;Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen;Advisory/Consultancy, Travel/Accommodation/Expenses: Astellas;Advisory/Consultancy, Travel/Accommodation/Expenses: Roche;Advisory/Consultancy: AstraZeneca;Advisory/Consultancy: Roche. T. Moran: Advisory/Consultancy: Roche;Advisory/Consultancy: Boehringer Ingelheim. D. Galetta: Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche;Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Boehringer Ingelheim;Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD;Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: BMS;Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca. F. Cappuzzo: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD. G. Robinet: Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche;Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD;Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZenaca;Advisory/Consultancy: BMS. S. Viteri: Full/Part-time employment: Pangaea Oncology;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche;Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AbbVie;Honoraria (self), Travel/Accommodation/Expenses: MSD;Research grant/Funding (institution), Travel/Accommodation/Expenses: Ose Immunotherapeutics;Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck KgaA;Research grant/Funding (institution): Janssen;Research grant/Funding (institution): Boehringer Ingelheim;Research grant/Funding (institution): Boston Pharmaceuticals Research grant/Funding (institution): Exelexis;Research grant/Funding (institution): Novocure;Research grant/Funding (institution): MedImmune. N. Peled: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca;Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Bayer;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Boehringer Ingelheim;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Lilly;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Foundation Medicine;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Guardian 360;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Genesort;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck KgaA;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): NovellusDx;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Takeda. D. Costantini: Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/Part-time employment, Officer/Board of Directors: OSEImmunotherapeutics. R. Dziadziuszko: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche;Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca;Honoraria (self): Pfizer;Honoraria (self): Novartis;Honoraria (self): MSD;Honoraria (self): Foundation Medicine;Honoraria (self), Advisory/Consultancy: Takeda;Advisory/Consultancy: Seattle Genetics. B. Besse: Research grant/Funding (institution): AbbVie;Research grant/Funding (institution): Amgen;Research grant/Funding (institution): AstraZeneca;Research grant/Funding (institution): Beigene;Research grant/Funding (institution): Blueprint Medicine;Research grant/Funding (institution): BMS;Research grant/Funding (institution): Boehringer Ingelheim;Research grant/Funding (institution): Cellgene;Research grant/Funding (institution): Cristal Therapeutics;Research grant/Funding (institution): Daichi-Sankyo;Research grant/Funding (institution): Elli-Lilly;Research grant/Funding (institution): GSK;Research grant/Funding (institution): Ignyta;Research grant/Funding (institution): Ipsen;Research grant/Funding (institution): Inivata;Research grant/Funding (institution): Janssen;Research grant/Funding (institution): Merck KgaA;Research grant/Funding (institution): MSD;Research grant/Funding (institution): Nektar;Research grant/Funding (institution): Onxeo;Research grant/Funding (institution): Ose Immunotherapeutics;Research grant/Funding (institution): Pfizer;Research grant/Funding (institution): PharmaMar;Research grant/Funding (institution): Roche-Genentech;Research grant/Funding (institution): Sanofi;Research grant/Funding (institution): Servier;Research grant/Funding (institution): Spectrum Pharmaceuticals;Research grant/Funding (institution): Takeda;Research grant/Funding (institution): Tiziana Pharma;Research grant/Funding (institution): Tolero Pharmaceuticals. All other authors have declared no conflicts of interest.