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

Effect of eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism: a randomized, double-blind, placebo-controlled trial

<p>Abstract</p> <p>Background</p> <p>Increasing evidence suggests the bidirectional interplay between parathyroid hormone and aldosterone as an important mechanism behind the increased risk of cardiovascular damage and bone disease observed in primary hyperparathyroidism. Our primary object is to assess the efficacy of the mineralocorticoid receptor-blocker eplerenone to reduce parathyroid hormone secretion in patients with parathyroid hormone excess.</p> <p>Methods/design</p> <p>Overall, 110 adult male and female patients with primary hyperparathyroidism will be randomly assigned to eplerenone (25 mg once daily for 4 weeks and 4 weeks with 50 mg once daily after dose titration] or placebo, over eight weeks. Each participant will undergo detailed clinical assessment, including anthropometric evaluation, 24-h ambulatory arterial blood pressure monitoring, echocardiography, kidney function and detailed laboratory determination of biomarkers of bone metabolism and cardiovascular disease.</p> <p>The study comprises the following exploratory endpoints: mean change from baseline to week eight in (1) parathyroid hormone(1–84) as the primary endpoint and (2) 24-h systolic and diastolic ambulatory blood pressure levels, NT-pro-BNP, biomarkers of bone metabolism, 24-h urinary protein/albumin excretion and echocardiographic parameters reflecting systolic and diastolic function as well as cardiac dimensions, as secondary endpoints.</p> <p>Discussion</p> <p>In view of the reciprocal interaction between aldosterone and parathyroid hormone and the potentially ensuing target organ damage, the EPATH trial is designed to determine whether eplerenone, compared to placebo, will effectively impact on parathyroid hormone secretion and improve cardiovascular, renal and bone health in patients with primary hyperparathyroidism.</p> <p>Trial registration</p> <p>ISRCTN33941607</p

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

Adjuvant hyperthermic intraperitoneal chemotherapy in patients with locally advanced colon cancer (COLOPEC): a multicentre, open-label, randomised trial

Background: Nearly a quarter of patients with locally advanced (T4 stage) or perforated colon cancer are at risk of developing peritoneal metastases, often without curative treatment options. We aimed to determine the efficacy of adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with locally advanced colon cancer. Methods: This multicentre, open-label trial was done in nine hospitals that specialised in HIPEC in the Netherlands. Patients with clinical or pathological T4N0–2M0-stage tumours or perforated colon cancer were randomly assigned (1:1), with a web-based randomisation application, before resection of the primary tumour, to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy (experimental group) or to adjuvant systemic chemotherapy alone (control group). Patients were stratified by tumour characteristic (T4 or perforation), age (<65 years or ≥65 years), and surgical approach of the primary tumour resection (laparoscopic or open). Key eligibility criteria included age between 18 and 75 years, adequate clinical condition for HIPEC, and intention to start adjuvant systemic chemotherapy. Patients with metastatic disease were ineligible. Adjuvant HIPEC consisted of fluorouracil (400 mg/m2) and leucovorin (20 mg/m2) delivered intravenously followed by intraperitoneal delivery of oxaliplatin (460 mg/m2) for 30 min at 42°C, delivered simultaneously or within 5–8 weeks after primary tumour resection. In all patients without evidence of recurrent disease at 18 months, a diagnostic laparoscopy was done. The primary endpoint was peritoneal metastasis free-survival at 18 months, measured in the intention-to-treat population, with the Kaplan-Meier method. Adverse events were assessed in all patients who received assigned treatment. This study is registered with ClinicalTrials.gov, number NCT02231086. Findings: Between April 1, 2015, and Feb 20, 2017, 204 patients were randomly assigned to treatment (102 in each group). In the HIPEC group, two patients withdrew consent after randomisation. In this group, 19 (19%) of 100 patients were diagnosed with peritoneal metastases: nine (47%) during surgical exploration preceding intentional adjuvant HIPEC, eight (42%) during routine follow-up, and two (11%) during diagnostic laparoscopy at 18-months. In the control group, 23 (23%) of 102 patients were diagnosed with peritoneal metastases, of whom seven (30%) were diagnosed by laparoscopy at 18-months and 16 during regular follow-up (therefore making them ineligible for diagnostic laparoscopy). In the intention-to-treat analysis (n=202), there was no difference in peritoneal-free survival at 18-months (80·9% [95% CI 73·3–88·5] for the experimental group vs 76·2% [68·0–84·4] for the control group, log-rank one-sided p=0·28). 12 (14%) of 87 patients who received adjuvant HIPEC developed postoperative complications and one (1%) encapsulating peritoneal sclerosis. Interpretation: In patients with T4 or perforated colon cancer, treatment with adjuvant HIPEC with oxaliplatin did not improve peritoneal metastasis-free survival at 18 months. Routine use of adjuvant HIPEC is not advocated on the basis of this trial. Funding: Organization for Health Research and Development and the Dutch Cancer Society