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Background Cancer and anti-cancer treatment (ACT) may be risk factors for severe SARS-CoV-2 infection and limited vaccine efficacy. Long–term longitudinal studies are needed to evaluate these risks. The Scottish COVID cancer immunity prevalence (SCCAMP) study characterizes the incidence and outcomes of SARS-CoV-2 infection and vaccination in patients with solid tumors undergoing ACT. This preliminary analysis includes 766 patients recruited since May 2020. Methods Patients with solid-organ cancers attending secondary care for active ACT consented to the collection of routine electronic health record data and serial blood samples over 12 months. Blood samples were tested for total SARS-CoV-2 antibody. Results A total of 766 participants were recruited between May 28, 2020 and October 31, 2021. Most received cytotoxic chemotherapy (79%). Among the participants, 48 (6.3%) were tested positive for SARS-CoV-2 by PCR. Infection rates were unaffected by ACT, largely aligning with the local population. Mortality proportion was not higher with a recent positive SARS-CoV-2 PCR (10.4% vs 10.6%). Multivariate analysis revealed lower infection rates in vaccinated patients regardless of chemotherapy (HR 0.307 [95% CI, 0.144-0.6548]) or immunotherapy (HR 0.314 [95% CI, 0.041-2.367]) treatment. A total of 96.3% of patients successfully raised SARS-CoV-2 antibodies after >2 vaccines. This was independent of the treatment type. Conclusion This is the largest on-going longitudinal real-world dataset of patients undergoing ACT during the early stages of the COVID-19 pandemic. This preliminary analysis demonstrates that patients with solid tumors undergoing ACT have high protection from SARS-CoV-2 infection following COVID-19 vaccination. The SCCAMP study will evaluate long–term COVID-19 antibody trends, focusing on specific ACTs and patient subgroups.

BackgroundAnthracycline-induced cardiotoxicity has a variable incidence, and the development of left ventricular dysfunction is preceded by elevations in cardiac troponin concentrations. Beta-adrenergic receptor blocker and renin-angiotensin-system inhibitor therapies have been associated with modest cardioprotective effects in unselected patients receiving anthracycline chemotherapy.MethodsIn a multicenter prospective randomized open label blinded endpoint trial, patients with breast cancer and non-Hodgkin lymphoma receiving anthracycline chemotherapy underwent serial high-sensitivity cardiac troponin testing and cardiac magnetic resonance imaging before and 6 months after anthracycline treatment. Patients at high risk of cardiotoxicity (cardiac troponin I concentrations in the upper tertile during chemotherapy) were randomized to standard care plus cardioprotection (combination carvedilol and candesartan therapy) or standard care alone. The primary outcome was adjusted change in left ventricular ejection fraction at 6 months. In low-risk non-randomized patients with cardiac troponin I concentrations in the lower two tertiles, we hypothesised the absence of a 6-month change in left ventricular ejection fraction (±2%).ResultsBetween October 2017 and June 2021, 175 patients (mean age 53 years; 87% female; 71% breast cancer) were recruited. Patients randomized to cardioprotection (n=29) or standard care (n=28) had left ventricular ejection fractions of 69.4±7.4% and 69.1±6.1% at baseline and 65.7±6.6% and 64.9±5.9% 6 months after completion of chemotherapy respectively. After adjusting for age, pre-treatment left ventricular ejection fraction and planned anthracycline dose, the estimated mean difference in 6-month left ventricular ejection fraction between cardioprotection and standard care groups was -0.37% (95% confidence interval, -3.59 to 2.85%; P=0.82). In low-risk non-randomized patients, baseline and 6-month left ventricular ejection fractions were 69.3±5.7% and 66.4±6.3% respectively: estimated mean difference, 2.87% (95% confidence interval, 1.63 to 4.10%; P=0.92, not equivalent)ConclusionsCombination candesartan and carvedilol therapy had no demonstrable cardioprotective effect in patients receiving anthracycline-based chemotherapy with high-risk on-treatment cardiac troponin I concentrations. Low-risk non-randomized patients had similar declines in left ventricular ejection fraction questioning the utility of routine cardiac troponin monitoring. Furthermore, the modest declines in left ventricular ejection fraction suggest that the value and clinical impact of early cardioprotection therapy needs to be better defined in patients receiving high-dose anthracycline regimes.REGISTRATIONEudraCT 2017-000896-99, ISRCTN24439460Clinical PerspectiveWhat is new?In this randomized controlled trial of patients at high risk of anthracycline cardiotoxicity, combined candesartan and carvedilol therapy did not protect against decline in 6-month left ventricular ejection fraction after completion of chemotherapy.Overall decline in 6-month left ventricular ejection fraction occurred irrespective of changes in cardiac troponin concentration during chemotherapy.What are the clinical implications?The Cardiac CARE trial findings do not support recent guideline recommendations advocating the use of cardiac troponin monitoring and early preventive neurohormonal blockade in patients at risk of anthracycline cardiotoxicity.Future studies should focus on factors determining transition to subsequent development of heart failure from initial mild and asymptomatic changes in cardiac function following anthracycline chemotherapy.

Background: Anthracyclines are effective cytotoxic drugs used in the treatment of breast cancer and lymphoma but are associated with myocardial injury, left ventricular dysfunction, and heart failure. Anthracycline-induced cardiotoxicity is highly variable in severity and without a proven therapeutic intervention. β-Adrenergic receptor blockers and renin-angiotensin-system inhibitor therapies have been associated with modest cardioprotective effects in unselected patients. Methods: The Cardiac CARE trial is a multicentre prospective randomized open-label blinded end point trial of combination β-adrenergic receptor blocker and renin-angiotensin-system inhibitor therapy in patients with breast cancer and non-Hodgkin lymphoma receiving anthracycline chemotherapy that is associated with myocardial injury. Patients at higher risk of cardiotoxicity with plasma high-sensitivity cTnI (cardiac troponin I) concentrations in the upper tertile at the end of chemotherapy are randomized to standard of care plus combination candesartan and carvedilol therapy or standard of care alone. All patients undergo cardiac magnetic resonance imaging before and 6 months after anthracycline treatment. The primary end point is the change in left ventricular ejection fraction at 6 months after chemotherapy. In low-risk nonrandomized patients, left ventricular ejection fraction before and 6 months after anthracycline will be compared with define the specificity of the high-sensitivity cTnI assay for identifying low-risk participants who do not develop left ventricular systolic dysfunction. Discussion: Cardiac CARE will examine whether cardiac biomarker monitoring identifies patients at risk of left ventricular dysfunction following anthracycline chemotherapy and whether troponin-guided treatment with combination candesartan and carvedilol therapy prevents the development of left ventricular dysfunction in these high-risk patients.

BACKGROUND Treatment advances have improved cancer-related outcomes and shifted interest towards minimising long-term iatrogenic complications, particularly chemotherapy-related cardiotoxicity. High-sensitivity cardiac troponin I (hs-cTnI) assays accurately quantify very low concentrations of plasma troponin and enable early detection of cardiomyocyte injury prior to development of myocardial dysfunction. The profile of hs-cTnI in response to anthracycline-based treatment has not previously been described. PATIENTS AND METHODS This was a multi-centre prospective observational cohort study. Female patients with newly-diagnosed invasive breast cancer scheduled to receive adjuvant or neo-adjuvant anthracycline-based (epirubicin) chemotherapy were recruited. Blood sampling was performed before, during and 24 hours after each treatment cycle. Plasma hs-cTnI concentrations were measured using the Abbott ARCHITECTSTAT assay (limit of detection 1.2 ng/L, coefficient of variation ≤10% at 4.7 ng/L, 99th centile upper reference limit in women 16 ng/L). RESULTS We recruited 78 women with a mean (standard deviation) age of 53.6 (9.6). The median (IQR) baseline troponin concentration was 1 (1 to 4) ng/L and median (IQR) cumulative epirubicin dose was 394 (300 to 405) mg/m2. Following an initial 33% fall 24 hours following anthracycline dosing (p Citation Format: Olga Oikonomidou, Evangelos Tzolos, Philip D Adamson, Peter S Hall, Iain R MacPherson, Morag MacLean, Steff Lewis, Heather McVicars, David E Newby, Nicholas L Mills, Ninian Lang, Peter A Henriksen. Dynamic changes in high-sensitivity cardiac troponin I in response to anthracycline-based chemotherapy-The Cardiac Care Trial pilot data [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-13-02.

BackgroundCancer and systemic anti-cancer treatment (SACT) have been identified as possible risk factors for infection and related severe illness associated with SARS-CoV-2 virus as a consequence of immune suppression. The Scottish COVID CAncer iMmunity Prevalence (SCCAMP) study aims to characterise the incidence and outcomes of SARS-Cov-2 infection in patients undergoing active anti-cancer treatment during the COVID-19 pandemic and their antibody response following vaccination.Patients and MethodsEligible patients were those attending secondary care for active anti-cancer treatment for a solid tumour. Blood samples were taken for total SARS-CoV-2 antibody assay (Siemens) at baseline and after 1.5, 3, 6 and 12 months. Data on COVID-19 infection, vaccination, cancer type, treatment and outcome was obtained from routine electronic health records.ResultsThe study recruited 766 eligible participants between 28th May 2020 and 31st October 2021. The median age was 62.7 years, and 66.5% were female. Most received cytotoxic chemotherapy (79%), with the remaining 14% receiving immunotherapy and 7% receiving another form of anti-cancer therapy (radiotherapy, other systemic anti-cancer treatment). 48 (6.3%) tested positive for SARS-CoV-2 by PCR during the study period. The overall infection rate matched that of the age-matched local general population until May 2021, after which population levels appeared higher. Antibody testing detected additional evidence of infection prior to vaccination, taking the total number to 58 (7.6%). There was no significant difference in SARS-CoV-2 PCR positive test rates based on type of anti-cancer treatment. Mortality proportion was similar between those who died within 90 days of a positive SARS-CoV-2 PCR and those with no positive PCR (10.4% vs 10.6%). Death from all causes was lowest among vaccinated patients, and of the patients who had a positive SARS-CoV-2 PCR at any time, all of those who died during the study period were unvaccinated. Multivariate analysis correcting for age, gender, socioeconomic status, comorbidities and number of previous medications revealed that vaccination was associated with a significantly lower infection rate regardless of treatment with chemotherapy or immunotherapy with hazard ratios of 0.307 (95% CI 0.144-0.6548) or 0.314 (95% CI 0.041-2.367) in vaccinated patients respectively. Where antibody data was available, 96.3% of patients successfully raised SARS-CoV-2 antibodies at a time point after vaccination. This was unaffected by treatment type.ConclusionSCCAMP provides real-world evidence that patients with cancer undergoing SACT have a high antibody response and protection from SARS-CoV-2 infection following COVID-19 vaccination.Highlights-The SCCAMP dataset represents the largest longitudinal study of patients with cancer undergoing anti-cancer treatment during the COVID-19 pandemic-Rates of infection in the cancer cohort mirrored those of the local age adjusted population-Vaccination was effective in patients with cancer undergoing active treatment in terms of antibody response and SARS-CoV-2 PCR rates-Treatment type did not impact the rate of SARS-CoV-2 antibody response

BACKGROUND Anthracyclines are widely used in the treatment of breast cancer and are well recognised to carry increased risk of cardiotoxicity. This can occur as an early, acute manifestation or many years after treatment as late onset cardiomyopathy. It is increasingly apparent that there may be a chronic subclinical phase associated with low grade cardiac injury with no apparent clinical impact on the contractile function of the heart. This period may remain latent for many years with the patient remaining asymptomatic and with apparently normal cardiac function. Identification of early and subtle cardiac dysfunction during this period could provide a window of opportunity for therapeutic intervention if those at risk or those experiencing this low-grade decline could be accurately identified. This study explores the potential utility of phosphorus magnetic resonance spectroscopy (31P-MRS) to identify very early anthracycline-induced cardiac toxicity and baseline predisposition to cardiac injury. This technique measures the phosphocreatine/adenosine triphosphate concentration ratio (PCr/ATP), which reflects cardiac cellular energetics. The normal range of PCr/ATP is approximately 1.8 - 2.2, whereas decreased PCr/ATP is associated with a drop in available energy reserve in the heart, associated with many forms of heart failure. Conventional cardiac investigations of electrocardiogram, multiple gated acquisition radionuclide scans (MUGA) and ultra-high sensitivity plasma cardiac troponin-I (cTn-I) have also been applied. METHODS 20 newly diagnosed breast cancer patients, receiving anthracycline-based chemotherapy, had magnetic resonance imaging to assess left ventricular ejection fraction and 31P magnetic resonance spectroscopy (31P MRS) to assess phosphocreatine to adenosine triphosphate concentration ratio (“PCr/ATP”). Measurements were performed pre-chemo, mid-chemo and post-chemo. Plasma high sensitivity cardiac troponin-I (cTn-I) and electrocardiograms were performed. RESULTS There was a significant negative correlation between change in PCr/ATP pre- to mid- chemo and change mid- to post-chemo (r=-0.68, p=0.04). Mean ejection fraction reduced significantly (5.1%) pre- to post-chemo (p=0.02). Change in PCr/ATP ratios pre- to post-chemo correlated inversely with changes in LVEF over the same period (r=-0.65, p=0.006) and mid- to post-chemotherapy (r=-0.77, p=0.002). Plasma cTn-I increased pre- to mid-chemo (1.35±0.81 to 4.40±2.64 ng/L; p=0.0001) and mid to post-chemo (4.40±2.64 to 18.33±13.23 ng/L; p=0.0001). CONCLUSIONS This study has demonstrated the use of 31P MRS in exploring cardiac energetics of breast cancer patients undergoing chemotherapy. Pre-chemotherapy PCr/ATP ratios were in line with healthy control values obtained using our system. This technique detected a pattern of recovery of PCr/ATP ratios following an initial 3 cycles of anthracyclines. Changes in PCr/ATP ratios were found to be significantly negatively correlated with changes in LVEF from pre to post chemotherapy. The significant decrease in LVEF from pre-post chemo may be due to the delayed response of LVEF to the initial 3 cycles of anthracyclines. Small but significant increases in plasma levels of cardiac troponin-I were observed early after initiation of anthracyclines. PCr/ATP ratios were not found to be related to cTn-I values but LVEF and cTn-I were found to be positively correlated. Future studies should take account of background factors that could influence cardiac PCr/ATP ratio such as age, physical fitness and regular medication whilst the improved sensitivity of 7T MRI scanners may also help in detecting earlier changes in cardiac energetics in this patient group. Citation Format: Olga Oikonomidou, Gillian Macnaught Macnaught, Christopher T Rodgers, William Clarke, Annette Cooper, Heather McVicars, Arran K Turnbull, Saeed Mirsadraee, Scott Semple, Martin Denvir. Association of cardiac energetics and plasma biomarkers with anthracycline-based chemotherapy in breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-01-03.

Treatment advances have improved cancer outcomes and shifted interest towards minimising iatrogenic complications. High-sensitivity cardiac troponin I (hs-cTnI) assays accurately quantify very low concentrations of troponin and may allow early detection of anthracycline-related myocyte injury.