A population-scale temporal case-control evaluation of COVID-19 disease phenotype and related outcome rates in patients with cancer in England (UKCCP).

Patients with cancer are at increased risk of hospitalisation and mortality following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the SARS-CoV-2 phenotype evolution in patients with cancer since 2020 has not previously been described. We therefore evaluated SARS-CoV-2 on a UK populationscale from 01/11/2020-31/08/2022, assessing case-outcome rates of hospital assessment(s), intensive care admission and mortality. We observed that the SARS-CoV-2 disease phenotype has become less severe in patients with cancer and the non-cancer population. Case-hospitalisation rates for patients with cancer dropped from 30.58% in early 2021 to 7.45% in 2022 while case-mortality rates decreased from 20.53% to 3.25%. However, the risk of hospitalisation and mortality remains 2.10x and 2.54x higher in patients with cancer, respectively. Overall, the SARS-CoV-2 disease phenotype is less severe in 2022 compared to 2020 but patients with cancer remain at higher risk than the non-cancer population. Patients with cancer must therefore be empowered to live more normal lives, to see loved ones and families, while also being safeguarded with expanded measures to reduce the risk of transmission.

Association of SARS-CoV-2 Spike Protein Antibody Vaccine Response With Infection Severity in Patients With Cancer: A National COVID Cancer Cross-sectional Evaluation.

Importance: Accurate identification of patient groups with the lowest level of protection following COVID-19 vaccination is important to better target resources and interventions for the most vulnerable populations. It is not known whether SARS-CoV-2 antibody testing has clinical utility for high-risk groups, such as people with cancer. Objective: To evaluate whether spike protein antibody vaccine response (COV-S) following COVID-19 vaccination is associated with the risk of SARS-CoV-2 breakthrough infection or hospitalization among patients with cancer. Design, Setting, and Participants: This was a population-based cross-sectional study of patients with cancer from the UK as part of the National COVID Cancer Antibody Survey. Adults with a known or reported cancer diagnosis who had completed their primary SARS-CoV-2 vaccination schedule were included. This analysis ran from September 1, 2021, to March 4, 2022, a period covering the expansion of the UK's third-dose vaccination booster program. Interventions: Anti-SARS-CoV-2 COV-S antibody test (Elecsys; Roche). Main Outcomes and Measures: Odds of SARS-CoV-2 breakthrough infection and COVID-19 hospitalization. Results: The evaluation comprised 4249 antibody test results from 3555 patients with cancer and 294 230 test results from 225 272 individuals in the noncancer population. The overall cohort of 228 827 individuals (patients with cancer and the noncancer population) comprised 298 479 antibody tests. The median age of the cohort was in the age band of 40 and 49 years and included 182 741 test results (61.22%) from women and 115 737 (38.78%) from men. There were 279 721 tests (93.72%) taken by individuals identifying as White or White British. Patients with cancer were more likely to have undetectable anti-S antibody responses than the general population (199 of 4249 test results [4.68%] vs 376 of 294 230 [0.13%]; P < .001). Patients with leukemia or lymphoma had the lowest antibody titers. In the cancer cohort, following multivariable correction, patients who had an undetectable antibody response were at much greater risk for SARS-CoV-2 breakthrough infection (odds ratio [OR], 3.05; 95% CI, 1.96-4.72; P < .001) and SARS-CoV-2-related hospitalization (OR, 6.48; 95% CI, 3.31-12.67; P < .001) than individuals who had a positive antibody response. Conclusions and Relevance: The findings of this cross-sectional study suggest that COV-S antibody testing allows the identification of patients with cancer who have the lowest level of antibody-derived protection from COVID-19. This study supports larger evaluations of SARS-CoV-2 antibody testing. Prevention of SARS-CoV-2 transmission to patients with cancer should be prioritized to minimize impact on cancer treatments and maximize quality of life for individuals with cancer during the ongoing pandemic.

An International Comparison of Presentation, Outcomes and CORONET Predictive Score Performance in Patients with Cancer Presenting with COVID-19 across Different Pandemic Waves.

Patients with cancer have been shown to have increased risk of COVID-19 severity. We previously built and validated the COVID-19 Risk in Oncology Evaluation Tool (CORONET) to predict the likely severity of COVID-19 in patients with active cancer who present to hospital. We assessed the differences in presentation and outcomes of patients with cancer and COVID-19, depending on the wave of the pandemic. We examined differences in features at presentation and outcomes in patients worldwide, depending on the waves of the pandemic: wave 1 D614G (n = 1430), wave 2 Alpha (n = 475), and wave 4 Omicron variant (n = 63, UK and Spain only). The performance of CORONET was evaluated on 258, 48, and 54 patients for each wave, respectively. We found that mortality rates were reduced in subsequent waves. The majority of patients were vaccinated in wave 4, and 94% were treated with steroids if they required oxygen. The stages of cancer and the median ages of patients significantly differed, but features associated with worse COVID-19 outcomes remained predictive and did not differ between waves. The CORONET tool performed well in all waves, with scores in an area under the curve (AUC) of >0.72. We concluded that patients with cancer who present to hospital with COVID-19 have similar features of severity, which remain discriminatory despite differences in variants and vaccination status. Survival improved following the first wave of the pandemic, which may be associated with vaccination and the increased steroid use in those patients requiring oxygen. The CORONET model demonstrated good performance, independent of the SARS-CoV-2 variants.

Establishment of CORONET, COVID-19 Risk in Oncology Evaluation Tool, to Identify Patients With Cancer at Low Versus High Risk of Severe Complications of COVID-19 Disease On Presentation to Hospital.

PURPOSE: Patients with cancer are at increased risk of severe COVID-19 disease, but have heterogeneous presentations and outcomes. Decision-making tools for hospital admission, severity prediction, and increased monitoring for early intervention are critical. We sought to identify features of COVID-19 disease in patients with cancer predicting severe disease and build a decision support online tool, COVID-19 Risk in Oncology Evaluation Tool (CORONET). METHODS: Patients with active cancer (stage I-IV) and laboratory-confirmed COVID-19 disease presenting to hospitals worldwide were included. Discharge (within 24 hours), admission (≥ 24 hours inpatient), oxygen (O2) requirement, and death were combined in a 0-3 point severity scale. Association of features with outcomes were investigated using Lasso regression and Random Forest combined with Shapley Additive Explanations. The CORONET model was then examined in the entire cohort to build an online CORONET decision support tool. Admission and severe disease thresholds were established through pragmatically defined cost functions. Finally, the CORONET model was validated on an external cohort. RESULTS: The model development data set comprised 920 patients, with median age 70 (range 5-99) years, 56% males, 44% females, and 81% solid versus 19% hematologic cancers. In derivation, Random Forest demonstrated superior performance over Lasso with lower mean squared error (0.801 v 0.807) and was selected for development. During validation (n = 282 patients), the performance of CORONET varied depending on the country cohort. CORONET cutoffs for admission and mortality of 1.0 and 2.3 were established. The CORONET decision support tool recommended admission for 95% of patients eventually requiring oxygen and 97% of those who died (94% and 98% in validation, respectively). The specificity for mortality prediction was 92% and 83% in derivation and validation, respectively. Shapley Additive Explanations revealed that National Early Warning Score 2, C-reactive protein, and albumin were the most important features contributing to COVID-19 severity prediction in patients with cancer at time of hospital presentation. CONCLUSION: CORONET, a decision support tool validated in health care systems worldwide, can aid admission decisions and predict COVID-19 severity in patients with cancer.

A Multicentre Retrospective Analysis of Toxicity in 6-weekly Versus 3-weekly Pembrolizumab.

Pembrolizumab is an anti-programmed cell death protein 1 immune checkpoint inhibitor with a dosing schedule of 200 mg 3 weekly (q3w). Dose of 400 mg 6 weekly (q6w) was approved based on simulation of dose/exposure relationships and predicted no difference in toxicity. We present real-world comparative toxicity data. Patients receiving pembrolizumab for any indication between March and December 2019 were included across 3 regional centers. Toxicity data were collected retrospectively using Common Terminology Criteria for Adverse Events, v5.0. Clinically significant immune-related adverse events (CSirAE) were defined as immune-related events and grade ≥3 rash. Data were analyzed using incidence (Poisson distribution) and incidence ratio. Overall, 63 patients started on q6w and 110 patients received q3w. There were 3 (q6w) and 8 (q3w) grade 3-5 CSirAE and 13 (q6w) and 31 (q3w) grade 1-2 CSirAE. The incidence of grade 3-5 CSirAE was 0.77 (95% confidence interval: 0.16-2.24) per 100 patient-months in q6w and 0.68 (95% confidence interval: 0.29-1.34) per 100 patient-months in q3w (incidence ratio of 1.13; 95% confidence interval: 0.19-4.70). Low-grade toxicity was common (fatigue, pruritus, rash; q6w 46%, q3w 42%). Incidence of CSirAEs was low but low-grade toxicity was common. Despite a limited number of events, there is the suggestion that the q6w schedule has a similar toxicity profile to q3w and therefore consideration should be given to the reduced burden to patients and health services when deciding treatment.

High flow or titrated oxygen for obese medical inpatients: a randomised crossover trial.

OBJECTIVE: To compare the effects on transcutaneous carbon dioxide tension (Ptco2) of high concentration and titrated oxygen therapy in medical inpatients with morbid obesity who were not selected for a pre-existing diagnosis of obesity hypoventilation syndrome. DESIGN: A randomised, crossover trial undertaken between February and September 2015. SETTING: Internal medicine service, Wellington Regional Hospital, New Zealand. PARTICIPANTS: 22 adult inpatients, aged 16 years or more, with a body mass index exceeding 40 kg/m2. INTERVENTIONS: Participants received in random order two 60-minute interventions, with a minimum 30-minute washout period between treatments: titrated oxygen therapy (oxygen delivered, if required, via nasal prongs to achieve peripheral oxygen saturation [Spo2] of 88-92%), and high concentration oxygen therapy (delivered via Hudson mask at 8 L/min, without regard to Spo2). Ptco2 and Spo2 were recorded at 10-minute intervals. MAIN OUTCOME MEASURE: Ptco2 at 60 minutes, adjusted for baseline. RESULTS: Baseline Ptco2 was 45 mmHg or lower for 16 participants with full data (73%). The mean difference in Ptco2 between high concentration and titrated oxygen therapy at 60 minutes was 3.2 mmHg (95% CI, 1.3-5.2 mmHg; P = 0.002). CONCLUSION: High concentration oxygen therapy increases Ptco2 in morbidly obese patients. Our findings support guidelines that advocate oxygen therapy, if required in patients with morbid obesity, be titrated to achieve a target Spo2 of 88-92%. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12610000522011.

Physiological effects of titrated oxygen via nasal high-flow cannulae in COPD exacerbations: A randomized controlled cross-over trial.

BACKGROUND AND OBJECTIVE: Increased arterial carbon dioxide tension (PaCO2 ) is an important complication of acute exacerbations of COPD. The effects of nasal high-flow cannulae (NHF) on PaCO2 in patients with COPD exacerbations, and whether this therapy should be used in this clinical situation, are less certain. We aimed to investigate the effect of NHF on PaCO2 in patients admitted to hospital with a COPD exacerbation. METHODS: We performed a single-centre randomized controlled cross-over trial in 24 hospital inpatients with acute exacerbations of COPD receiving oxygen via standard nasal prongs (SNPs). Patients received both supplemental oxygen via NHF (35 L/min) and SNP for 30 min each, with oxygen titrated to maintain the patient's baseline oxygen saturation, measured by pulse oximetry (SpO2 ). Interventions were administered in random order with a minimum 15-min washout between interventions. The primary outcome was difference in transcutaneous carbon dioxide tension (PtCO2 ) at 30 min adjusted for time zero. RESULTS: The difference in PtCO2 adjusted for time zero was lower after 30 min for NHF compared with SNP (-1.4 mm Hg (95% CI: -2.2 to -0.6), P = 0.001). There was no difference in SpO2 at 30 min (-0.02% (95% CI: -0.8 to 0.7), P = 0.96). The reduction in respiratory rate for NHF at 30 min was not statistically significant (-2.0 breaths/min (95% CI: -4.5 to 0.4), P = 0.099). CONCLUSION: Short-term use of NHF results in a small reduction in PtCO2 compared with SNP in patients with acute exacerbations of COPD, but whether this is clinically significant is uncertain.

Target oxygen saturation range: 92-96% Versus 94-98.

This scientific letter considers the rationale for the target oxygen saturation measured by pulse oximetry (SpO2 ) range of 92-96% for oxygen therapy in adult patients without COPD or other conditions associated with chronic respiratory failure, recommended by the Thoracic Society of Australia and New Zealand, in contrast to the 94-98% target range recommended by the British Thoracic Society. We conclude from the available evidence that the SpO2 target of 92-96% may be preferable to 94-98%.

Thoracic Society of Australia and New Zealand oxygen guidelines for acute oxygen use in adults: 'Swimming between the flags'.

The purpose of the Thoracic Society of Australia and New Zealand guidelines is to provide simple, practical evidence-based recommendations for the acute use of oxygen in adults in clinical practice. The intended users are all health professionals responsible for the administration and/or monitoring of oxygen therapy in the management of acute medical patients in the community and hospital settings (excluding perioperative and intensive care patients), those responsible for the training of such health professionals, and both public and private health care organizations that deliver oxygen therapy.