Changes in the Management of Patients having Radical Radiotherapy for Lung Cancer during the First Wave of the COVID-19 Pandemic in the UK.

AIMS: In response to the COVID-19 pandemic, guidelines on reduced fractionation for patients treated with curative-intent radiotherapy were published, aimed at reducing the number of hospital attendances and potential exposure of vulnerable patients to minimise the risk of COVID-19 infection. We describe the changes that took place in the management of patients with stage I-III lung cancer from April to October 2020. MATERIALS AND METHODS: Lung Radiotherapy during the COVID-19 Pandemic (COVID-RT Lung) is a prospective multicentre UK cohort study. The inclusion criteria were: patients with stage I-III lung cancer referred for and/or treated with radical radiotherapy between 2nd April and 2nd October 2020. Patients who had had a change in their management and those who continued with standard management were included. Data on demographics, COVID-19 diagnosis, diagnostic work-up, radiotherapy and systemic treatment were collected and reported as counts and percentages. Patient characteristics associated with a change in treatment were analysed using multivariable binary logistic regression. RESULTS: In total, 1553 patients were included (median age 72 years, 49% female); 93 (12%) had a change to their diagnostic investigation and 528 (34%) had a change to their treatment from their centre's standard of care as a result of the COVID-19 pandemic. Age ≥70 years, male gender and stage III disease were associated with a change in treatment on multivariable analysis. Patients who had their treatment changed had a median of 15 fractions of radiotherapy compared with a median of 20 fractions in those who did not have their treatment changed. Low rates of COVID-19 infection were seen during or after radiotherapy, with only 21 patients (1.4%) developing the disease. CONCLUSIONS: The COVID-19 pandemic resulted in changes to patient treatment in line with national recommendations. The main change was an increase in hypofractionation. Further work is ongoing to analyse the impact of these changes on patient outcomes.

A novel use for routine CBCT imaging during radiotherapy to detect COVID-19.

INTRODUCTION: Thoracic CT is a useful tool in the early diagnosis of patients with COVID-19. Typical appearances include patchy ground glass shadowing. Thoracic radiotherapy uses daily cone beam CT imaging (CBCT) to check for changes in patient positioning and anatomy prior to treatment through a qualitative assessment of lung appearance by radiographers. Observation of changes related to COVID-19 infection during this process may facilitate earlier testing improving patient management and staff protection. METHODS: A tool was developed to create overview reports for all CBCTs for each patient throughout their treatment. Reports contain coronal maximum intensity projection (MIP's) of all CBCTs and plots of lung density over time. A single therapeutic radiographer undertook a blinded off-line audit that reviewed 150 patient datasets for tool optimisation in which medical notes were compared to image findings. This cohort included 75 patients treated during the pandemic and 75 patients treated between 2014 and 2017. The process was repeated retrospectively on a subset of the 285 thoracic radiotherapy patients treated between January-June 2020 to assess the efficiency of the tool and process. RESULTS: Three patients in the n = 150 optimisation cohort had confirmed COVID-19 infections during their radiotherapy. Two of these were detected by the reported image assessment process. The third case was not detected on CBCT due to minimal density changes in the visible part of the lungs. Within the retrospective cohort four patients had confirmed COVID-19 based on RT-PCR tests, three of which were retrospectively detected by the reported process. CONCLUSION: The preliminary results indicate that the presence of COVID-19 can be detected on CBCT by therapeutic radiographers. IMPLICATIONS FOR PRACTICE: This process has now been extended to clinical service with daily assessments of all thoracic CBCTs. Changes noted are referred for oncologist review.

Longitudinal characterisation of haematological and biochemical parameters in cancer patients prior to and during COVID-19 reveals features associated with outcome.

BACKGROUND: Cancer patients are at increased risk of death from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cancer and its treatment affect many haematological and biochemical parameters, therefore we analysed these prior to and during coronavirus disease 2019 (COVID-19) and correlated them with outcome. PATIENTS AND METHODS: Consecutive patients with cancer testing positive for SARS-CoV-2 in centres throughout the United Kingdom were identified and entered into a database following local governance approval. Clinical and longitudinal laboratory data were extracted from patient records. Data were analysed using Mann-Whitney U test, Fisher's exact test, Wilcoxon signed rank test, logistic regression, or linear regression for outcomes. Hierarchical clustering of heatmaps was performed using Ward's method. RESULTS: In total, 302 patients were included in three cohorts: Manchester (n = 67), Liverpool (n = 62), and UK (n = 173). In the entire cohort (N = 302), median age was 69 (range 19-93 years), including 163 males and 139 females; of these, 216 were diagnosed with a solid tumour and 86 with a haematological cancer. Preinfection lymphopaenia, neutropaenia and lactate dehydrogenase (LDH) were not associated with oxygen requirement (O2) or death. Lymphocyte count (P < 0.001), platelet count (P = 0.03), LDH (P < 0.0001) and albumin (P < 0.0001) significantly changed from preinfection to during infection. High rather than low neutrophils at day 0 (P = 0.007), higher maximal neutrophils during COVID-19 (P = 0.026) and higher neutrophil-to-lymphocyte ratio (NLR; P = 0.01) were associated with death. In multivariable analysis, age (P = 0.002), haematological cancer (P = 0.034), C-reactive protein (P = 0.004), NLR (P = 0.036) and albumin (P = 0.02) at day 0 were significant predictors of death. In the Manchester/Liverpool cohort 30 patients have restarted therapy following COVID-19, with no additional complications requiring readmission. CONCLUSION: Preinfection biochemical/haematological parameters were not associated with worse outcome in cancer patients. Restarting treatment following COVID-19 was not associated with additional complications. Neutropaenia due to cancer/treatment is not associated with COVID-19 mortality. Cancer therapy, particularly in patients with solid tumours, need not be delayed or omitted due to concerns that treatment itself increases COVID-19 severity.

Longitudinal analysis of biochemical and haematological features of cancer patients with COVID-19

Background: Cancer patients (pts) are at increased risk of severe COVID-19 infection and death. Older pts, men and those with haematological malignancies and receiving anti-tumour therapy within 14 days appear to be at highest risk for poor outcomes. In general populations, severe COVID-19 infection has been associated with neutrophilia, raised lactate dehydrogenase (LDH) and C-reactive protein (CRP). Cancer and its treatment affect many haematological and biochemical parameters. We examined whether COVID-19 infection affected these compared to pts’ baseline parameters by longitudinal tracking. We also investigated whether changes were associated with poor outcome. Methods: Consecutive pts with solid or haematological malignancies presenting with index symptoms and testing positive for SARS-CoV-2 at a tertiary oncology centre were identified following institutional board approval. Clinical and laboratory data were extracted from the pt record. Paired T-tests were used for longitudinal sampling and ANOVA/Chi squared for outcomes. Results: 52 pts tested positive (27 male, 25 female;median age 63). 80.5% had solid cancers, and 19.5% haematological. 31/52 pts were lymphopenic prior to infection. Comparing mean pre-infection counts (6 months-14 days=PRE) with mean counts from the 5 days following positive test (DURING) lymphocyte counts significantly decreased during infection (p<0.0001). Platelets were significantly reduced DURING vs. PRE COVID-19 (p=0.0028). 17/52 pts developed transient (median 2 days) neutropenia (<2x109/L) DURING infection (6 pts <1x109/L, 2 pts <0.5x109/L), 8/17 attributed to cancer/cancer therapy, the rest had no underlying cause. 8/17 pts received growth factor support. Reduced lymphocytes/neutrophils/platelets at diagnosis were not associated with oxygen requirement (O2) or death. Different CRP trajectories were observed when comparing pts grouped by discharge/ O2/death. Higher CRP and LDH at diagnosis were associated with admission (p=0.02 CRP/0.2 LDH), O2 (p=0.0002 CRP/p<0.01 LDH) and death (p=0.069 CRP/p=0.04 LDH). Updated analysis will be presented. Conclusions: Infection with SARS-CoV-2 commonly affects haematological parameters in cancer pts. High CRP and LDH are associated with poor outcomes. Legal entity responsible for the study: The Christie NHS Foundation Trust. Funding: Has not received any funding. Disclosure: R. Lee: Speaker Bureau/Expert testimony, Research grant/Funding (self): Bristol Myers Squibb;Speaker Bureau/Expert testimony: Astra Zeneca. A. Armstrong: Shareholder/Stockholder/Stock options, Husband has shares: Astra Zeneca. T. Cooksley: Speaker Bureau/Expert testimony: Bristol Myers Squibb. All other authors have declared no conflicts of interest.