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The coronavirus disease 2019 (COVID-19) pandemic may have affected cancer management. We aimed to evaluate changes in every oncology care pathway essential steps, from screening to treatment during the pandemic. Monthly oncological activity differences between 2019 and 2020 (screening tests, histopathological analyzes, multidisciplinary tumor board meetings (MTMB), diagnostic announcement procedures (DAP), and treatments) were calculated in two French areas experiencing different pandemic's intensity (Reims and Colmar). COVID-19 has had a dramatic impact in terms of screening (-86% to-100%), diagnosis (-39%) , and surgical treatment (-30%). This global decrease in all essential oncology care pathway steps contrasted with the relative stability of chemotherapy (-9%) and radiotherapy use (-16%). Outbreak occurred earlier and with more intensity in Colmar but had a comparable impact in both areas regarding MTBM and DAP. The current ONCOCARE-COV study is still in progress, and with a longer follow-up to analyze post-lockdown situation. The Oncologist 2020;9999:• •

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Acute inflammation causes endothelial dysfunction, which is partly mediated by oxidant stress and inactivation of nitric oxide. The contribution of depletion of tetrahydrobiopterin (BH(4)), the cofactor required for nitric oxide generation, is unclear. In this randomized, double-blind, three-way crossover study, forearm blood flow (FBF) responses to ACh and glyceryltrinitrate (GTN) were measured before and 3.5 h after infusion of Escherichia coli endotoxin (LPS, 20 IU/kg iv) in eight healthy men. The effect of intra-arterial BH(4) (500 microg/min), placebo, or vitamin C (24 mg/min) was studied on separate days 3.5 h after LPS infusion. In addition, human umbilical vein endothelial cells were incubated for 24 h with vitamin C and LPS. ACh and GTN caused dose-dependent forearm vasodilation. The FBF response to ACh, which was decreased by 23 +/- 17% (P < 0.05) by LPS infusion, was restored to baseline reactivity by BH(4) and vitamin C. FBF responses to GTN were not affected by BH(4) or vitamin C. LPS increased leukocyte count, high-sensitivity C-reactive protein, IL-6, IL-1beta, IFN-gamma, monocyte chemoattractant protein-1, pulse rate, and body temperature and decreased platelet count and vitamin C concentration. Vitamin C increased forearm plasma concentration of BH(4) by 32% (P < 0.02). Incubation with LPS and vitamin C, but not LPS alone, increased intracellular BH(4) concentration in human umbilical vein endothelial cells. Impaired endothelial function during acute inflammation can be restored by BH(4) or vitamin C. Vitamin C may exert some of its salutary effects by increasing BH(4) concentration.

Background. The COVID-19 pandemic caused major oncology care pathway disruption. The CAPANCOVID study aimed to evaluate the impact on pancreatic adenocarcinoma (PA) – from diagnosis to treatment – of the reorganisation of the health care system during the first lockdown. Methods. This multicentre ambispective observational study included 833 patients diagnosed with PA between September 1 st , 2019 and October 31 st , 2020 from 13 French centres. Data were compared over three periods defined as before the outbreak of COVID-19, during the first lockdown (March 1 st to May 11 th , 2020) and after lockdown. Results. During the lockdown, mean weekly number of new cases decreased compared with that of pre-pandemic levels (13.2 vs. 10.8, -18.2%; p=0.63) without rebound in the post-lockdown period (13.2 vs. 12.9, -1.7%; p=0.97). The number of borderline tumours increased (13.6% to 21.7%) whereas the rate of metastatic diseases rate dropped (47.1% to 40.3%) (p=0.046). Time-to-diagnosis and -treatment were not different over periods. Waiting neoadjuvant chemotherapy in resectable tumours was significantly favoured (24.7% to 32.6%) compared with upfront surgery (13% to 7.8%) (p=0.013). The use of mFOLFIRINOX preoperative chemotherapy regimen decreased (84.9% to 69%; p=0.044). After lockdown, the number of borderline tumours decreased (21.7% to 9.6%) and advanced diseases increased (59.7% to 69.8%) (p=0.046). SARS-CoV-2 infected 39 patients (4.7%) causing 5 deaths (12.8%). Conclusion. This cohort study suggests the existence of missing diagnoses and of a shift in disease stage at diagnosis from resectable to advanced diseases with related therapeutic modifications whose prognostic consequences will be known after the planned follow-up.