Life-prolonging treatment restrictions and outcomes in patients with cancer and COVID-19:an update from the Dutch Oncology COVID-19 Consortium

AIM OF THE STUDY: The coronavirus disease 2019 (COVID-19) pandemic significantly impacted cancer care. In this study, clinical patient characteristics related to COVID-19 outcomes and advanced care planning, in terms of non-oncological treatment restrictions (e.g. do-not-resuscitate codes), were studied in patients with cancer and COVID-19. METHODS: The Dutch Oncology COVID-19 Consortium registry was launched in March 2020 in 45 hospitals in the Netherlands, primarily to identify risk factors of a severe COVID-19 outcome in patients with cancer. Here, an updated analysis of the registry was performed, and treatment restrictions (e.g. do-not-intubate codes) were studied in relation to COVID-19 outcomes in patients with cancer. Oncological treatment restrictions were not taken into account. RESULTS: Between 27th March 2020 and 4th February 2021, 1360 patients with cancer and COVID-19 were registered. Follow-up data of 830 patients could be validated for this analysis. Overall, 230 of 830 (27.7%) patients died of COVID-19, and 60% of the remaining 600 patients with resolved COVID-19 were admitted to the hospital. Patients with haematological malignancies or lung cancer had a higher risk of a fatal outcome than other solid tumours. No correlation between anticancer therapies and the risk of a fatal COVID-19 outcome was found. In terms of end-of-life communication, 50% of all patients had restrictions regarding life-prolonging treatment (e.g. do-not-intubate codes). Most identified patients with treatment restrictions had risk factors associated with fatal COVID-19 outcome. CONCLUSION: There was no evidence of a negative impact of anticancer therapies on COVID-19 outcomes. Timely end-of-life communication as part of advanced care planning could save patients from prolonged suffering and decrease burden in intensive care units. Early discussion of treatment restrictions should therefore be part of routine oncological care, especially during the COVID-19 pandemic

Dutch Oncology COVID-19 consortium:Outcome of COVID-19 in patients with cancer in a nationwide cohort study

Aim of the study: Patients with cancer might have an increased risk for severe outcome of coronavirus disease 2019 (COVID-19). To identify risk factors associated with a worse outcome of COVID-19, a nationwide registry was developed for patients with cancer and COVID-19. Methods: This observational cohort study has been designed as a quality of care registry and is executed by the Dutch Oncology COVID-19 Consortium (DOCC), a nationwide collaboration of oncology physicians in the Netherlands. A questionnaire has been developed to collect pseudonymised patient data on patients' characteristics, cancer diagnosis and treatment. All patients with COVID-19 and a cancer diagnosis or treatment in the past 5 years are eligible. Results: Between March 27th and May 4th, 442 patients were registered. For this first analysis, 351 patients were included of whom 114 patients died. In multivariable analyses, age ≥65 years (p < 0.001), male gender (p = 0.035), prior or other malignancy (p = 0.045) and active diagnosis of haematological malignancy (p = 0.046) or lung cancer (p = 0.003) were independent risk factors for a fatal outcome of COVID-19. In a subgroup analysis of patients with active malignancy, the risk for a fatal outcome was mainly determined by tumour type (haematological malignancy or lung cancer) and age (≥65 years). Conclusion: The findings in this registry indicate that patients with a haematological malignancy or lung cancer have an increased risk of a worse outcome of COVID-19. During the ongoing COVID-19 pandemic, these vulnerable patients should avoid exposure to severe acute respiratory syndrome coronavirus 2, whereas treatment adjustments and prioritising vaccination, when available, should also be considered

Normal bacterial uptake and killing by PMN from CD patients.

<p>Isolated PMN were challenged with opsonised GFP-expressing <i>E. coli</i> for 15 minutes at 37°C after which GFP fluorescence was determined by FACs analysis. Appropriate 0 °C control was taken for each experiment. (A) Mean±SEM of median fluorescence intensity (MFI) of PMN from CD patients (n=16) and HC (n=14) is shown. (B) Percentage of PMN positive for <i>E. coli</i>–GFP (%) of 16 CD patients and 14 HC. (C) PMN were challenged with <i>E. coli</i> for 15 minutes at 37°C and allowed to kill bacteria for 4 hours at 37°C. Colonies grown from lysed PMN after 15 hours were counted using a colony counter. Mean±SEM of CD patients (n=10) and HC (n=9) is shown.</p

PMN from CD patients are deficient in trans-epithelial migration towards IL8.

<p>(A) The involvement of ERK1/2 and PI3K pathways in IL8-induced migration was confirmed by measuring the percentage of migrated PMN after incubation with or without 10 µM of U0126 and LY294002, respectively. Mean±SEM is shown (n=3). (B) PMN were stimulated with 20 ng/ml of IL8 for the indicated time points. Experiments were performed on healthy controls (HC) and CD PMN simultaneously, and samples were loaded side-by-side on the same gel. ERK1/2 and AKT activation were detected by their phospho-specific antibodies. Representative example is shown. (C) No differences in levels of activated ERK1/2 were observed between CD patients and HC (n=10, mean±SEM shown) upon quantification of blots by densitometry. (D) No differences in levels of activated AKT were observed between CD patients and HC (n=10, mean±SEM shown) upon quantification of blots by densitometry. (E) PMN from HC and CD patients were applied to the upper compartment of a transwell system. PMN transmigrated in response to 20 ng/ml IL8 present in the lower compartment were counted by flow cytometry and results are represented as percentage of those migrated in control wells. No differences were observed between Mean±SEM of CD patients (n=11) and HC (n=8). (F) PMN from healthy and CD patients were allowed to migrate through a monolayer of epithelial cells towards IL8 for 4 hours at 37°C. Compared to HC PMN, CD PMN showed significantly less migration (Mean±SEM, *p=0.02, n=10).</p

Impaired survival signalling in CD PMN does not affect intermediate and end-stage apoptosis.

<p>(A) Isolated PMN were cultured either with or without 100 ng/ml Fas-Ab (6 hours) or 10 ng/ml GMCSF (15 hours) and the percentage of apoptotic PMN was determined by Annexin V positivity (9 CD patients and 8 HC). (B) No differences in DNA fragmentation as measured by TUNEL assay after 15 hours of PMN culture with or without 10 ng/ml GMCSF were observed between CD and HC (n=6). (C-F) PMN were isolated simultaneously from a CD patient and healthy control, stimulated with 5 ng/ml GMCSF for 15 minutes and samples were run on one gel. (C) STAT3 activation was detected by western blotting using phospho-STAT3 antibodies. Representative experiment is shown. (D) Significantly decreased levels of activated STAT3 were observed in CD patients compared to HC (mean±SEM, *p=0.04, n=5). Total STAT3 levels were unchanged (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0084521#pone-0084521-g002" target="_blank">Figure 2A and F</a>). (E) AKT activation was detected by western blotting using phospho-AKT antibodies Representative experiment is shown. (F) Protein levels of activated AKT were quantified by densitometry and corrected for β-actin protein levels. Mean±SEM of CD patients and HC is shown (n=5). </p

Enhanced fMLP-induced ROS production in CD patients corresponds with increased ERK and AKT signalling.

<div><p>(A) PMN production of superoxide after stimulation was measured by flow cytometry analysis and expressed as a percentage of the fluorescence in unstimulated cells. Mean±SEM of CD patients and HC is shown. Asterisks indicate significantly higher ROS production in fMLP stimulated cells in CD patients compared to HCs (*p=0.03, n=14). Preincubation of PMN with 5ng/ml GMCSF enhanced fMLP-induced ROS production, to an equal maximum in CD patients and healthy controls. (B) Isolated PMN from CD and HC were simultaneously stimulated with 1 µM fMLP with or without priming with 5ng/ml of GMCSF. Phosphorylated ERK1/2 and AKT (upper panels) was detected by Western blot analysis. Membranes were reprobed with antibodies against β-actin (lower panel) to confirm equal loading. (C) Quantification of blots shows that fMLP-induced phosphorylation of AKT is significantly increased in CD patients compared to HC PMN (mean±SEM, *p=0.03, n=9).</p> <p>(D) Quantification of blots shows that fMLP-induced phosphorylation of ERK1/2 is significantly increased in CD patients compared to HC PMN (mean±SEM, *p=0.03, n=9). </p></div

Life-prolonging treatment restrictions and outcomes in patients with cancer and COVID-19: an update from the Dutch Oncology COVID-19 Consortium

AIM OF THE STUDY: The coronavirus disease 2019 (COVID-19) pandemic significantly impacted cancer care. In this study, clinical patient characteristics related to COVID-19 outcomes and advanced care planning, in terms of non-oncological treatment restrictions (e.g. do-not-resuscitate codes), were studied in patients with cancer and COVID-19. METHODS: The Dutch Oncology COVID-19 Consortium registry was launched in March 2020 in 45 hospitals in the Netherlands, primarily to identify risk factors of a severe COVID-19 outcome in patients with cancer. Here, an updated analysis of the registry was performed, and treatment restrictions (e.g. do-not-intubate codes) were studied in relation to COVID-19 outcomes in patients with cancer. Oncological treatment restrictions were not taken into account. RESULTS: Between 27th March 2020 and 4th February 2021, 1360 patients with cancer and COVID-19 were registered. Follow-up data of 830 patients could be validated for this analysis. Overall, 230 of 830 (27.7%) patients died of COVID-19, and 60% of the remaining 600 patients with resolved COVID-19 were admitted to the hospital. Patients with haematological malignancies or lung cancer had a higher risk of a fatal outcome than other solid tumours. No correlation between anticancer therapies and the risk of a fatal COVID-19 outcome was found. In terms of end-of-life communication, 50% of all patients had restrictions regarding life-prolonging treatment (e.g. do-not-intubate codes). Most identified patients with treatment restrictions had risk factors associated with fatal COVID-19 outcome. CONCLUSION: There was no evidence of a negative impact of anticancer therapies on COVID-19 outcomes. Timely end-of-life communication as part of advanced care planning could save patients from prolonged suffering and decrease burden in intensive care units. Early discussion of treatment restrictions should therefore be part of routine oncological care, especially during the COVID-19 pandemic

Benefit of earlier anti-TNF treatment on IBD disease complications?

Background: Anti-tumour necrosis factor [anti-TNF] treatment was demonstrated to have disease-modifying abilities in inflammatory bowel disease [IBD]. In this study, we aimed to determine the effect of anti-TNF treatment timing on IBD disease complications and mucosal healing [MH]. Methods: The following IBD-related complications were tested in relation to timing of anti-TNF therapy start in newly diagnosed IBD patients [n = 413]: Fistula formation, abscess formation, extra-intestinal manifestations [EIM], surgery, referral to academic centre, and MH. Results: A total of 85 patients [21%] received anti-TNF (66 Crohn's disease [CD], 16 ulcerative colitis [UC], 3 inflammatory bowel disease unclassified [IBDU]) of whom 57% [48 patients] were treated 16 months] regarding gender, age, smoking status, and familial IBD. More importantly, patients receiving anti-TNF early did not suffer less IBD-related complications during follow-up as compared with patients started on anti-TNF late, nor was more MH observed. Similar results were obtained when anti-TNF treated patient were stratified more stringently, ie 2 4 months [24 patients]. Cox regression analysis showed no beneficial correlations between anti-TNF timing and IBD-related complications. Anti-TNF treated patients achieving MH were 11 times less likely to develop EIMs compared with patients who did not achieved MH while on anti-TNF. Conclusions: This study was unable to confirm a benefit of earlier anti-TNF treatment on IBD disease complications. This could be explained by more aggressive treatment earlier in disease, resulting in fewer IBD complications. However, it seems more likely that inappropriate selection of patients for therapy leads to suboptimal treatment and subsequently suboptimal outcome

Life-prolonging treatment restrictions and outcomes in patients with cancer and COVID-19: an update from the Dutch Oncology COVID-19 Consortium

Aim of the study: The coronavirus disease 2019 (COVID-19) pandemic significantly impacted cancer care. In this study, clinical patient characteristics related to COVID-19 outcomes and advanced care planning, in terms of non-oncological treatment restrictions (e.g. do-not-resuscitate codes), were studied in patients with cancer and COVID-19. Methods: The Dutch Oncology COVID-19 Consortium registry was launched in March 2020 in 45 hospitals in the Netherlands, primarily to identify risk factors of a severe COVID-19 outcome in patients with cancer. Here, an updated analysis of the registry was performed, and treatment restrictions (e.g. do-not-intubate codes) were studied in relation to COVID-19 outcomes in patients with cancer. Oncological treatment restrictions were not taken into account. Results: Between 27th March 2020 and 4th February 2021, 1360 patients with cancer and COVID-19 were registered. Follow-up data of 830 patients could be validated for this analysis. Overall, 230 of 830 (27.7%) patients died of COVID-19, and 60% of the remaining 600 patients with resolved COVID-19 were admitted to the hospital. Patients with haematological malignancies or lung cancer had a higher risk of a fatal outcome than other solid tumours. No correlation between anticancer therapies and the risk of a fatal COVID-19 outcome was found. In terms of end-of-life communication, 50% of all patients had restrictions regarding life-prolonging treatment (e.g. do-not-intubate codes). Most identified patients with treatment restrictions had risk factors associated with fatal COVID-19 outcome. Conclusion: There was no evidence of a negative impact of anticancer therapies on COVID-19 outcomes. Timely end-of-life communication as part of advanced care planning could save patients from prolonged suffering and decrease burden in intensive care units. Early discussion of treatment restrictions should therefore be part of routine oncological care, especially during the COVID-19 pandemic

Life-prolonging treatment restrictions and outcomes in patients with cancer and COVID-19: an update from the Dutch Oncology COVID-19 Consortium

Aim of the study: The coronavirus disease 2019 (COVID-19) pandemic significantly impacted cancer care. In this study, clinical patient characteristics related to COVID-19 outcomes and advanced care planning, in terms of non-oncological treatment restrictions (e.g. do-not-resuscitate codes), were studied in patients with cancer and COVID-19. Methods: The Dutch Oncology COVID-19 Consortium registry was launched in March 2020 in 45 hospitals in the Netherlands, primarily to identify risk factors of a severe COVID-19 outcome in patients with cancer. Here, an updated analysis of the registry was performed, and treatment restrictions (e.g. do-not-intubate codes) were studied in relation to COVID-19 outcomes in patients with cancer. Oncological treatment restrictions were not taken into account. Results: Between 27th March 2020 and 4th February 2021, 1360 patients with cancer and COVID-19 were registered. Follow-up data of 830 patients could be validated for this analysis. Overall, 230 of 830 (27.7%) patients died of COVID-19, and 60% of the remaining 600 patients with resolved COVID-19 were admitted to the hospital. Patients with haematological malignancies or lung cancer had a higher risk of a fatal outcome than other solid tumours. No correlation between anticancer therapies and the risk of a fatal COVID-19 outcome was found. In terms of end-of-life communication, 50% of all patients had restrictions regarding life-prolonging treatment (e.g. do-not-intubate codes). Most identified patients with treatment restrictions had risk factors associated with fatal COVID-19 outcome. Conclusion: There was no evidence of a negative impact of anticancer therapies on COVID-19 outcomes. Timely end-of-life communication as part of advanced care planning could save patients from prolonged suffering and decrease burden in intensive care units. Early discussion of treatment restrictions should therefore be part of routine oncological care, especially during the COVID-19 pandemic