Specialist palliative and end-of-life care for patients with cancer and SARS-CoV-2 infection: a European perspective

Background: Specialist palliative care team (SPCT) involvement has been shown to improve symptom control and end-of-life care for patients with cancer, but little is known as to how these have been impacted by the COVID-19 pandemic. Here, we report SPCT involvement during the first wave of the pandemic and compare outcomes for patients with cancer who received and did not receive SPCT input from multiple European cancer centres. Methods: From the OnCovid repository (N = 1318), we analysed cancer patients aged ⩾18 diagnosed with COVID-19 between 26 February and 22 June 2020 who had complete specialist palliative care team data (SPCT+ referred; SPCT− not referred). Results: Of 555 eligible patients, 317 were male (57.1%), with a median age of 70 years (IQR 20). At COVID-19 diagnosis, 44.7% were on anti-cancer therapy and 53.3% had ⩾1 co-morbidity. Two hundred and six patients received SPCT input for symptom control (80.1%), psychological support (54.4%) and/or advance care planning (51%). SPCT+ patients had more ‘Do not attempt cardio-pulmonary resuscitation’ orders completed prior to (12.6% versus 3.7%) and during admission (50% versus 22.1%, p < 0.001), with more SPCT+ patients deemed suitable for treatment escalation (50% versus 22.1%, p < 0.001). SPCT involvement was associated with higher discharge rates from hospital for end-of-life care (9.7% versus 0%, p < 0.001). End-of-life anticipatory prescribing was higher in SPCT+ patients, with opioids (96.3% versus 47.1%) and benzodiazepines (82.9% versus 41.2%) being used frequently for symptom control. Conclusion: SPCT referral facilitated symptom control, emergency care and discharge planning, as well as high rates of referral for psychological support than previously reported. Our study highlighted the critical need of SPCTs for patients with cancer during the pandemic and should inform service planning for this population

Systemic pro-inflammatory response identifies patients with cancer with adverse outcomes from SARS-CoV-2 infection: the OnCovid Inflammatory Score

Background: Cancer patients are particularly susceptible to SARS-CoV-2 infection. The systemic inflammatory response is a pathogenic mechanism shared by cancer progression and Covid-19. We investigated systemic inflammation as a driver of severity and mortality from Covid-19, evaluating the prognostic role of commonly utilized inflammatory indices in SARS-CoV-2-infected cancer patients accrued to the OnCovid study. Methods: In a multi-center cohort of SARS-CoV-2-infected cancer patients in Europe, we evaluated dynamic changes in neutrophil-lymphocyte ratio (NLR); platelet-lymphocyte ratio (PLR); prognostic nutritional index (PNI), renamed the OnCovid Inflammatory Score (OIS); modified Glasgow prognostic score (mGPS); and prognostic index (PI) in relationship to oncological and Covid-19 infection features, testing their prognostic potential in independent training (n=529) and validation (n=542) sets. Results: We evaluated 1,071 eligible patients: 625 (58.3%) males, 420 with malignancy in advanced stage (39.2%), most commonly genitourinary (n=216, 20.2%). 844 (78.8%) had ≥1 comorbidity and 754 (70.4%) ≥1 Covid-19 complication. NLR, OIS, and mGPS worsened at Covid-19 diagnosis compared to pre-Covid-19 measurement (P<0.01), recovering in survivors to pre-Covid-19 levels. Patients in poorer risk categories for each index except the PLR exhibited higher mortality rates (P<0.001) and shorter median overall survival in the training and validation sets (P<0.01). Multivariable analyses revealed the OIS to be most independently predictive of survival (validation set HR 2.48, 95% CI 1.47 – 4.20, P=0.001; adjusted C-index 0.611). Conclusions: Systemic inflammation is a validated prognostic domain in SARS-CoV-2-infected cancer patients and can be utilized as a bedside predictor of adverse outcome. Lymphocytopenia and hypoalbuminemia as computed by the OIS are independently predictive of severe Covid-19, supporting their use for risk stratification. Reversal of the Covid-19-induced pro-inflammatory state is a putative therapeutic strategy in patients with cancer

Autosomal dominant limb girdle myopathy with ragged-red fibers and cardiomyopathy - A pedigree study by in vivo P-31-MR spectroscopy indicating a multisystem mitochondrial defect

We describe a late-onset autosomal dominant limb girdle myopathy, associated with dilated cardiomyopathy and mental deterioration. In two affected members of the pedigree with histochemical (ragged-red and cytocrome c oxidase - negative fibers) and ultrastructural abnormalities of muscle mitochondria, in vivo muscle phosphorus MR spectroscopy disclosed a slow rate of phosphocreatine resynthesis after exercise. Brain phosphorus MR spectroscopy revealed a defect of the energy metabolism in the two patients and in a third asymptomatic member, as shown by a significantly low phosphocreatine, increased ADP and decreased phosphorylation potential. Molecular analysis of muscle mitochondrial DNA failed to reveal any known mutation, including multiple deletions of the mtDNA which have been associated with some autosomal dominant mitochondrial diseases. The multisystem clinical involvement, the presence of ragged-red fibers and the alterations revealed by in vivo brain and muscle P-31-MRS suggest that this limb-girdle syndrome represents an unusual phenotype of mitochondrial cytopathy

Prior immune checkpoint inhibitor (ICI) therapy is associated with decreased COVID-19-related hospitalizations and complications in patients with cancer: Results of a propensity-matched analysis of the OnCovid registry

Objectives: To date, studies have not provided definitive answers regarding whether previous immune checkpoint inhibitor (ICI) treatment alters outcomes for cancer patients with COVID-19. Methods: The OnCovid registry (NCT04393974) was searched from February 27, 2020, to January 31, 2022, for patients who received systemic anti-cancer therapy in the 4 weeks before laboratory-confirmed COVID-19 diagnosis. Propensity-score matching using country, vaccination status, primary tumor type, sex, age, comorbidity burden, tumor stage, and remission status investigated differences in predefined clinical outcomes comparing those who had or had not received ICIs. Results: Of 3523 patients screened, 137 ICI-only and 1378 non-ICI met inclusion criteria. Before matching, ICI patients were older, male, enrolled at centers in Italy, and had histories of smoking, thoracic cancers, advanced cancer stages, and active malignancies (P ≤0.02). After matching, there were 120 ICI and 322 non-ICI patients. ICI patients had no differences (odds ratio: 95% CI) in presenting COVID-19 symptoms (0.69: 0.37-1.28), receipt of COVID-specific therapy (0.88: 0.54-1.41), 14-day (0.95: 0.56-1.61), or 28-day (0.79: 0.48-1.29) mortalities. However, ICI patients required less COVID-19-related hospitalization (0.37: 0.21-0.67) and oxygen therapy (0.51: 0.31-0.83) and developed fewer complications (0.57: 0.36-0.92). Conclusion: In this propensity-score matched analysis, previous ICI therapy did not worsen and potentially improved COVID-19 outcomes in patients with cancer