Background Cancer patients are thought to have an increased risk of developing severe Coronavirus Disease 2019 (COVID-19) infection and of dying from the disease. In this work, predictive factors for COVID-19 severity and mortality in cancer patients were investigated. Patients and Methods In this large nationwide retro-prospective cohort study, we collected data on patients with solid tumours and COVID-19 diagnosed between March 1 and June 11, 2020. The primary endpoint was all-cause mortality and COVID-19 severity, defined as admission to an intensive care unit (ICU) and/or mechanical ventilation and/or death, was one of the secondary endpoints. Results From April 4 to June 11, 2020, 1289 patients were analysed. The most frequent cancers were digestive and thoracic. Altogether, 424 (33%) patients had a severe form of COVID-19 and 370 (29%) patients died. In multivariate analysis, independent factors associated with death were male sex (odds ratio 1.73, 95%CI: 1.18-2.52), ECOG PS ≥ 2 (OR 3.23, 95%CI: 2.27-4.61), updated Charlson comorbidity index (OR 1.08, 95%CI: 1.01-1.16) and admission to ICU (OR 3.62, 95%CI 2.14-6.11). The same factors, age along with corticosteroids before COVID-19 diagnosis, and thoracic primary tumour site were independently associated with COVID-19 severity. None of the anticancer treatments administered within the previous 3 months had any effect on mortality or COVID-19 severity, except cytotoxic chemotherapy in the subgroup of patients with detectable SARS-CoV-2 by RT-PCR, which was associated with a slight increase of the risk of death (OR 1.53; 95%CI: 1.00-2.34; p = 0.05). A total of 431 (39%) patients had their systemic anticancer treatment interrupted or stopped following diagnosis of COVID-19. Conclusions Mortality and COVID-19 severity in cancer patients are high and are associated with general characteristics of patients. We found no deleterious effects of recent anticancer treatments, except for cytotoxic chemotherapy in the RT-PCR-confirmed subgroup of patients. In almost 40% of patients, the systemic anticancer therapy was interrupted or stopped after COVID-19 diagnosis.

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Introduction: The incidence of neuroendocrine tumors (NETs) is rising, especially in elderly patients. The elderly cancer population presents considerable challenges, yet little is known about the characteristics, treatment patterns, and outcomes of metastatic NET (mNET) patients. Methods: The Lyon Real-life Evidence in Metastatic NeuroEndocrine Tumors study (LyREMeNET, NCT03863106) included consecutive mNET patients, diagnosed between January 1990 and December 2017. The exclusion criteria were nonmetastatic NET, poorly differentiated neuroendocrine carcinoma, and mixed neuroendocrine-nonneuroendocrine neoplasms. We aimed to compare patients ≥70 years old to patients < 70 years old. Results: A total of 866 patients were included, 198 (23%) were ≥70 years old. There was no significant differ-

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t AbstractIn a previous study, we demonstrated that the Men1 gene is mainly expressed in the proliferative crypt compartment of the small intestine and that a reduction of menin expression in the crypt-like IEC-17 cell line induces an increase in proliferation rate concomitant with an increase in cyclin D1 expression. The aim of the present study was to test the hypothesis that the NF-kB pathway may be involved in cyclin D1 overexpression.Transcriptional activity of the cyclin D1 gene promoter was increased upon reduction of menin expression. Blockade of the NF-kB pathway restored proliferation, cell cycle, cyclin D1 gene transcription and cyclin D1 expression levels to those observed in the presence of menin. These data support a correlation between cyclin D1 expression, NF-kB activity and menin expression in this epithelial cell line and are relevant to the physiological function of menin in regulating proliferation in the intestinal epithelium.