Impact of the COVID-19 Pandemic on Outcomes for Patients with Lung Cancer Receiving Curative-intent Radiotherapy in the UK.

AIMS: Previous work found that during the first wave of the COVID-19 pandemic, 34% of patients with lung cancer treated with curative-intent radiotherapy in the UK had a change to their centre's usual standard of care treatment (Banfill et al. Clin Oncol 2022;34:19-27). We present the impact of these changes on patient outcomes. MATERIALS AND METHODS: The COVID-RT Lung database was a prospective multicentre UK cohort study including patients with stage I-III lung cancer referred for and/or treated with radical radiotherapy between April and October 2020. Data were collected on patient demographics, radiotherapy and systemic treatments, toxicity, relapse and death. Multivariable Cox and logistic regression were used to assess the impact of having a change to radiotherapy on survival, distant relapse and grade ≥3 acute toxicity. The impact of omitting chemotherapy on survival and relapse was assessed using multivariable Cox regression. RESULTS: Patient and follow-up forms were available for 1280 patients. Seven hundred and sixty-five (59.8%) patients were aged over 70 years and 603 (47.1%) were female. The median follow-up was 213 days (119, 376). Patients with stage I-II non-small cell lung cancer (NSCLC) who had a change to their radiotherapy had no significant increase in distant relapse (P = 0.859) or death (P = 0.884); however, they did have increased odds of grade ≥3 acute toxicity (P = 0.0348). Patients with stage III NSCLC who had a change to their radiotherapy had no significant increase in distant relapse (P = 0.216) or death (P = 0.789); however, they did have increased odds of grade ≥3 acute toxicity (P < 0.001). Patients with stage III NSCLC who had their chemotherapy omitted had no significant increase in distant relapse (P = 0.0827) or death (P = 0.0661). CONCLUSION: This study suggests that changes to radiotherapy and chemotherapy made in response to the COVID-19 pandemic did not significantly affect distant relapse or survival. Changes to radiotherapy, namely increased hypofractionation, led to increased odds of grade ≥3 acute toxicity. These results are important, as hypofractionated treatments can help to reduce hospital attendances in the context of potential future emergency situations.

Artificial Intelligence for Radiotherapy Auto-Contouring: Current Use, Perceptions of and Barriers to Implementation.

AIMS: Artificial intelligence has the potential to transform the radiotherapy workflow, resulting in improved quality, safety, accuracy and timeliness of radiotherapy delivery. Several commercially available artificial intelligence-based auto-contouring tools have emerged in recent years. Their clinical deployment raises important considerations for clinical oncologists, including quality assurance and validation, education, training and job planning. Despite this, there is little in the literature capturing the views of clinical oncologists with respect to these factors. MATERIALS AND METHODS: The Royal College of Radiologists realises the transformational impact artificial intelligence is set to have on our specialty and has appointed the Artificial Intelligence for Clinical Oncology working group. The aim of this work was to survey clinical oncologists with regards to perceptions, current use of and barriers to using artificial intelligence-based auto-contouring for radiotherapy. Here we share our findings with the wider clinical and radiation oncology communities. We hope to use these insights in developing support, guidance and educational resources for the deployment of auto-contouring for clinical use, to help develop the case for wider access to artificial intelligence-based auto-contouring across the UK and to share practice from early-adopters. RESULTS: In total, 78% of clinical oncologists surveyed felt that artificial intelligence would have a positive impact on radiotherapy. Attitudes to risk were more varied, but 49% felt that artificial intelligence will decrease risk for patients. There is a marked appetite for urgent guidance, education and training on the safe use of such tools in clinical practice. Furthermore, there is a concern that the adoption and implementation of such tools is not equitable, which risks exacerbating existing inequalities across the country. CONCLUSION: Careful coordination is required to ensure that all radiotherapy departments, and the patients they serve, may enjoy the benefits of artificial intelligence in radiotherapy. Professional organisations, such as the Royal College of Radiologists, have a key role to play in delivering this.

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.

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.

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.

Cardiovascular mortality and morbidity following radical radiotherapy for lung cancer: Is cardiovascular death under-reported?

BACKGROUND: Lung cancer is the most common malignancy worldwide. Radical radiotherapy is an essential treatment in the management of early and locally advanced lung cancer. Cardiac events are known to occur following radical radiotherapy for lung cancer. This study examines the burden of cardiac events post radiotherapy, and estimates the accuracy of death certification in patients who received radical radiotherapy for lung cancer. METHODS: We conducted a retrospective observational cohort study for all patients receiving radical radiotherapy for non-small cell lung cancer (NSCLC) at a large cancer centre between 01/01/2010 to 31/12/2016. Baseline cardiovascular disease and cancer status and treatment data were collected, along with hospital admission data and documented cause of death from the national registry for a median follow-up period of 34 months. RESULTS: Of 1224 patients included in the analysis, 378 (30.9%) patients had cardiovascular disease at baseline, including 140 (11.4%) with prior myocardial infarction. In the 846 patients without known cardiovascular disease, 451 (53.3%) had a QRISK2 predicted 10-year cardiovascular risk >20% over 10 years. During follow-up, 215 hospitalisations occurred (Incidence rate 6.2 per hundred patient years) which were classified as primarily cardiac, and 622 patients died (18 per 100 patient-years). However, death certificates stated a primary cardiac cause of death in only 33 cases (5.3% of deaths). Notably, 29% of patients dying out of hospital and certified as cancer death did not have documented cancer relapse prior to death, and 61% had no community palliative care input prior to death, implying these events may have been sudden and unexpected. CONCLUSION: There is a high prevalence of baseline cardiovascular disease in people undergoing radiotherapy for NSCLC, accompanied by significant rates of post-radiotherapy cardiovascular hospitalisation. However, only a small proportion of deaths are attributed to cardiovascular disease, together with the large amount of sudden deaths observed, this suggests that cardiovascular death is greatly under-reported in official statistics.