Impact of Covid-19 on lung cancer and mesothelioma specialist nurses: A survey of experiences and perceptions.

PURPOSE: The covid-19 global pandemic has impacted on nurses who have rapidly adapted to new ways of working, and experienced negative impacts due to over-stretched services. Two surveys captured the experiences of lung cancer and mesothelioma specialist nurses in the United Kingdom (UK) in 2020, but the impact of later stages of the pandemic was unknown. This study aimed to explore the impact of covid-19 on lung Cancer and mesothelioma nurses since January 2021, the second wave of the pandemic. METHODS: An online cross-sectional survey with both open and closed questions explored the impact of covid-19 on ways of working and workload, quality of care, and health and wellbeing. The survey was open to UK based lung cancer and mesothelioma advanced or specialist nurses. RESULTS: 85 nurses responded to the survey. The majority were Clinical Nurse Specialists, based in England. Respondents reported changes in ways of working due to redeployment, staff shortages, and home working. Widespread adoption of virtual working practices led to concerns of negative impacts. Perceived excessive workload impacted on care with two-thirds of the sample (57, 67%) reporting they had been unable to provide the same quality of care to patients. Impacts on nurses' health and wellbeing were reported with two-thirds of the sample (56, 66%) reporting a deterioration in emotional wellbeing and mental health. Coping mechanisms employed included online team support to share experiences and increased uptake of exercise; however, impacts on lifestyle and access to coping mechanisms varied. CONCLUSION: Nurses have stepped up to the challenges of the pandemic with teamwork and innovation, but pressure arising from the pandemic and high workloads led to negative impacts on wellbeing. The authors have provided recommendations to improve patient care and support the wellbeing of nurses, which will be key to a resilient workforce living with covid-19. Whilst this study focussed on lung cancer and mesothelioma specialists, the findings have wider implications for other cancer specialties.

Understanding clinical decision-making in mesothelioma care: a mixed methods study.

INTRODUCTION: Malignant pleural mesothelioma is a rare, incurable cancer arising from previous asbestos exposure; patients have a poor prognosis, with a median survival rate of 8-14 months. Variation in mesothelioma clinical decision-making remains common with a lack of multidisciplinary knowledge sharing, leading to inconsistencies in treatment decisions. The study aimed to explore which factors impacted on clinicians' decision-making in mesothelioma care, with a view to optimising the mesothelioma care pathway. METHODS: This mixed methods study consisted of documentary analysis of local and national guidelines, policies or documents pertaining to mesothelioma care pathways, secondary analysis of mesothelioma patient data, and interviews with clinicians attending lung cancer and/or mesothelioma-specific multidisciplinary team meetings. The study took place at three National Health Service trusts in England. Documentations relating to patients' treatment pathways were collated and reviewed qualitatively. Records of patients with mesothelioma were extracted from hospital patient records and data collected on diagnosis date, treatment, mortality rates, survival postdiagnosis, age and clinical care team. Data were statistically analysed. Interviews with clinicians explored influences on clinical decision-making, including challenges or barriers involved. Data were thematically analysed. The Strengthening the Reporting of Observational Studies in Epidemiology reporting checklist was used. RESULTS: There were differences in the structure and delivery of mesothelioma treatment and care between trusts. Four main themes were identified: 'collaboration and communication', 'evidence base and knowledge', 'role of the clinician' and 'role of the patient'. Two cross-cutting themes relating to the role of the mesothelioma nurse specialist and the impact of COVID-19 were identified. DISCUSSION: There is a need to review the structure of mesothelioma multidisciplinary team meetings to ensure patients are reviewed by clinicians with appropriate knowledge, expertise and understanding of how, why and when decisions should be made. There is a need for expert clinicians in mesothelioma care to promote an up-to-date evidence and knowledge base within the wider multidisciplinary team.

Long-term benefit of lurbinectedin as palliative chemotherapy in progressive malignant pleural mesothelioma (MPM): final efficacy and translational data of the SAKK 17/16 study.

BACKGROUND: The SAKK 17/16 study showed promising efficacy data with lurbinectedin as second- or third-line palliative therapy in malignant pleural mesothelioma. Here, we evaluated long-term outcome and analyzed the impact of lurbinectedin monotherapy on the tumor microenvironment at the cellular and molecular level to predict outcomes. MATERIAL AND METHODS: Forty-two patients were treated with lurbinectedin in this single-arm study. Twenty-nine samples were available at baseline, and seven additional matched samples at day one of cycle two of treatment. Survival curves and rates between groups were compared using the log-rank test and Kaplan-Meier method. Statistical significance was set at P value <0.05. RESULTS: Updated median overall survival (OS) was slightly increased to 11.5 months [95% confidence interval (CI) 8.8-13.8 months]. Thirty-six patients (85%) had died. The OS rate at 12 and 18 months was 47% (95% CI 32.1% to 61.6%) and 31% (95% CI 17.8% to 45.0%), respectively. Median progression-free survival was 4.1 months (95% CI 2.6-5.5 months). No new safety signals were observed. Patients with lower frequencies of regulatory T cells, as well as lower tumor-associated macrophages (TAMs) at baseline, had a better OS. Comparing matched biopsies, a decrease of M2 macrophages was observed in five out of seven patients after exposure to lurbinectedin, and two out of four patients showed increased CD8+ T-cell infiltrates in tumor. DISCUSSION: Lurbinectedin continues to be active in patients with progressing malignant pleural mesothelioma. According to our very small sample size, we hypothesize that baseline TAMs and regulatory T cells are associated with survival. Lurbinectedin seems to inhibit conversion of TAMs to M2 phenotype in humans.

Clinical nurse specialist role in providing generalist and specialist palliative care: A qualitative study of mesothelioma clinical nurse specialists.

AIM: To explore perspectives of Mesothelioma UK clinical nurse specialists (CNSs) on their role in providing palliative care for patients with mesothelioma and their families. DESIGN: A qualitative descriptive approach using focus group and interview methods. METHODS: Focus groups and semi-structured interviews were conducted with 16 Mesothelioma UK clinical nurse specialists using the online software Google Meet. Data collection was carried out in Jan-Feb 2021 and data were analysed using thematic analysis. The consolidated criteria for reporting qualitative research (COREQ) was used as the reporting guideline for this paper. RESULTS: Four main themes were identified from the data: Mesothelioma UK clinical nurse specialist role in relation to palliative care; joint working with specialist palliative care and community services; patients and family carer's willingness to engage with palliative care services; and the impact of COVID-19 on palliative care for mesothelioma patients. CONCLUSION: This study provides valuable insights into palliative care needs in mesothelioma. Patients with mesothelioma and their families have significant palliative care needs throughout the course of their illness from diagnosis to the end of life. Mesothelioma UK CNS's play a crucial role in supporting patients' and families palliative care needs, and are highly skilled in providing this care. IMPACT: By acknowledging the role of Mesothelioma UK CNS's in palliative care provision, and supporting collaborative working between specialist and generalist palliative care providers, there is the capacity to significantly improve palliative care in mesothelioma and improve outcomes for patients and their families.

The impact of COVID-19 on new mesothelioma diagnoses in Italy.

BACKGROUND: The aim of this work was to evaluate the impact of the restrictions put in place to control the COVID-19 pandemic on new diagnoses of malignant mesothelioma (MM) in Italy. METHODS: Twelve of the 21 Italian malignant mesothelioma CORs (regional operating centres) participated. The study included all cases of MM with microscopic confirmation; cases without microscopic confirmation and death certificate only (DCO) were excluded. For each case, information on sex, date of birth, tumor site, morphology, and date of diagnosis was retrieved. We compared the number of incident cases in 2020 with 2019, looking at the overall picture and for four periods: pre-pandemic (January-February), first wave (March-May), low incidence (June-September), and second wave (October-December). RESULTS: A total of 604 cases were registered: 307 in 2019 and 297 in 2020. In the 2020 pre-pandemic period, the incidence was higher than in the same months in 2019 (+45%); there was no significant change during the first wave (+1%) or in the low-incidence period (-3%), while a decrease was observed during the second wave (-32%). However, the data were not homogeneous across the country: the increase in the pre-pandemic period concerned mostly the regions of northern (+61.5%) and central Italy (+43.5%); during the first wave, MM diagnoses increased in the northern (+38.5%) and central (+11.4%) regions but decreased in the southern regions (-52.9%). All these differences are compatible with random fluctuations. CONCLUSION: The COVID-19 pandemic had little or no impact on new MM diagnoses, and variations were not homogeneous throughout the country.

NIPU: a randomised, open-label, phase II study evaluating nivolumab and ipilimumab combined with UV1 vaccination as second line treatment in patients with malignant mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and aggressive tumour. For patients with inoperable disease, few treatment options are available after first line chemotherapy. The combination of ipilimumab and nivolumab has recently shown increased survival compared to standard chemotherapy, but most patients do not respond and improvements are called for. Telomerase is expressed in mesothelioma cells, but only sparsely in normal tissues and is therefore an attractive target for therapeutic vaccination. Vaccination against telomerase is tolerable and has shown to induce immune responses associated with increased survival in other cancer types. There is a well-founded scientific rationale for the combination of a telomerase vaccine and checkpoint inhibition to improve treatment response in MPM patients. METHODS: NIPU is a randomized, multi-centre, open-label, phase II study comparing the efficacy and safety of nivolumab and ipilimumab with or without telomerase vaccine in patients with inoperable malignant pleural mesothelioma after first-line platinum-based chemotherapy. Participants (n = 118) are randomized 1:1 into two treatment arms. All participants receive treatment with nivolumab (240 mg every 2 weeks) and ipilimumab (1 mg/kg every 6 weeks) until disease progression, unacceptable toxicity or for a maximum of 2 years. Patients randomised to the experimental arm receive 8 intradermal injections of UV1 vaccine during the first three months of treatment. Tumour tissue, blood, urine, faeces and imaging will be collected for biomarker analyses and exploration of mechanisms for response and resistance to therapy. DISCUSSION: Checkpoint inhibition is used for treatment of mesothelioma, but many patients still do not respond. Increasing therapy response to immunotherapy is an important goal. Possible approaches include combination with chemotherapy, radiotherapy, targeted therapy and other immunotherapeutic agents. Predictive biomarkers are necessary to ensure optimal treatment for each patient and to prevent unnecessary side effects. This trial seeks to improve treatment response by combining checkpoint inhibition with a telomerase vaccine and also to explore mechanisms for treatment response and resistance. Knowledge gained in the NIPU study may be transferred to the first line setting and to other cancers with limited benefit from immunotherapy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04300244, registered March 8th, 2020, https://clinicaltrials.gov/ct2/show/NCT04300244?term=NIPU&draw=2&rank=1 .

Incidental connection: Cancer and caregiving during COVID-19.

In this brief article, the author describes how her husband was first diagnosed with mesothelioma, an incidental finding of routine medical testing. His first surgery was timed to the beginnings of coronavirus (COVID) lockdown. The staging of his cancer aligned with a new stage of the pandemic, and by the time of his first chemotherapy appointment, patients were no longer allowed to bring family along for outpatient visits. Although the author is an expert and educator on psychosocial care in medicine, she has found herself at a complete loss, teaching herself the ropes of how to connect with his treatment team and practicing ambiguous advo cacy. Her hus band will be in recovery for a long time; they will both be in recovery. Mesothelioma has robbed them of certainty and safety, as cancer often does, and just as COVID has done, to everyone. We are all living in the question mark, in the ambiguity-the Con nection is our loneliness, our isolation, and the uncertainty. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

County-Level Longitudinal Clustering of COVID-19 Mortality to Incidence Ratio in the United States (preprint)

Background: As of November 12, 2020, the mortality to incidence ratio (MIR) of COVID-19 was 5.8% in the US. We utilized a longitudinal model-based clustering system based on the disease trajectories over time. We aimed to find the so-called “vulnerable” cluster of counties where to dedicate additional resources by the US policymakers.  Methods: County-level COVID-19 cases and deaths (Mar-Nov 2020), and a set of potential risk factors were collected for 3050 U.S. counties during the 1st wave (Mar25-Jun3, 2020), 1344 counties (sunbelt region) during the 2nd wave (Jun4-Sep2, 2020), and 1055 counties (great plains) during the 3rd wave (Sep3-Nov12, 2020). We used growth mixture models to identify clusters of counties exhibiting similar COVID-19 MIR growth trajectories and risk-factors over time. Results: We identified the so-called “more vulnerable” clusters during the 1st, 2nd and 3rd waves of COVID-19. Tuberculosis (OR=1.3-2.1-3.2), drug use disorder (OR=1.1), hepatitis (OR=13.1), HIV/AIDS (OR=2.3), cardiomyopathy and myocarditis (OR=1.3), diabetes (OR=1.2), mesothelioma (OR=9.3) were significantly associated with increased odds of being in a more vulnerable cluster. Heart complications and cancer were the main risk factors increasing the COVID-19 MIR (range: 0.08%-0.52% MIR↑).Conclusion: We identified the so-called “more vulnerable” county-clusters exhibiting the highest COVID-19 MIR trajectories, indicating that enhancing the capacity and access to healthcare resources would be key to successfully manage COVID-19 in these clusters. These findings provide insights for public health policymakers on the groups of people and locations they need to pay particular attention while managing the COVID-19 epidemic.