Blaes, Anne

Abstract BackgroundRe-allocation of resources during the COVID-19 pandemic has resulted in delays in care delivery to patients with cardiovascular disease and cancer. The ability of health care providers to provide optimal care in this setting has not been formally evaluated.ObjectivesTo assess the impact of COVID-19 resource re-allocation on scheduling, testing, elective procedures, telemedicine access, use of new COVID-19 therapies, and providers’ opinions on healthcare policies among oncology and cardiology practitioners.MethodsAn electronic survey was conducted by a cardio-oncology collaborative network through regional and state chapters of the American College of Cardiology , American Society of Clinical Oncology, and the International Cardio-Oncology Society. Descriptive statistics were reported by frequency and proportion for analyses, and stratified categorically by geographic region and specialty.Results1,415 providers (43 countries) participated: 986 cardiologists, 306 oncologists, and 118 trainees/internal medicine. 63% (195/306) of oncologists vs 92% (896/976) of cardiologists reported cancellations of treatments/elective procedures (p=0.01). 46% (442/970) of cardiologists and 25% (76/303) of oncologists modified the scope of their practice (p=<0.001). Academic physicians (74.5%) felt better supplied with personal protective equipment (PPE) vs non-academic (74.5% vs 67.2%; p=0.018). Telemedicine was less common in Europe 81% (74/91), and Latin America 64% (101/158), than the United States, 88% (950/1,097) (p=<0.001). 95% of all groups supported more active leadership from medical professional societies.ConclusionsThese results support initiatives to promote expanded coverage for telemedicine, increased access to PPE, better testing availability and involvement of medical professional societies to help with preparedness for future health care crisis.Appendix: Link to the Survey: https://www.surveymonkey.com/r/C8ZDYNW

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS–CoV‐2) has given rise to a pandemic of unprecedented proportions in the modern era because of its highly contagious nature and impact on human health and society: coronavirus disease 2019 (COVID‐19). Patients with cardiovascular (CV) risk factors and established CV disease (CVD) are among those initially identified at the highest risk for serious complications, including death. Subsequent studies have pointed out that patients with cancer are also at high risk for a critical disease course. Therefore, the most vulnerable patients are seemingly those with both cancer and CVD, and a careful, unified approach in the evaluation and management of this patient population is especially needed in times of the COVID‐19 pandemic. This review provides an overview of the unique implications of the viral outbreak for the field of cardio‐oncology and outlines key modifications in the approach to this ever‐increasing patient population. These modifications include a shift toward greater utilization of cardiac biomarkers and a more focused CV imaging approach in the broader context of modifications to typical practice pathways. The goal of this strategic adjustment is to minimize the risk of SARS–CoV‐2 infection (or other future viral outbreaks) while not becoming negligent of CVD and its important impact on the overall outcomes of patients who are being treated for cancer.

Background: The National Comprehensive Cancer Network and American Society of Clinical Oncology recommend consideration of the use of echocardiography 6 to 12 months after completion of anthracycline-based chemotherapy in at-risk populations. Assessment of BNP (B-type natriuretic peptide) has also been suggested by the American College of Cardiology/American Heart Association/Heart Failure Society of America for the identification of Stage A (at risk) heart failure patients. The real-world frequency of the use of these tests in patients after receipt of anthracycline therapy, however, has not been studied previously. Methods and Results: In this retrospective study, using administrative claims data from the OptumLabs Data Warehouse, we identified 31 447 breast cancer and lymphoma patients (age ≥18 years) who were treated with an anthracycline in the United States between January 1, 2008 and January 31, 2018. Continuous medical and pharmacy coverage was required for at least 6 months before the initial anthracycline dose and 12 months after the final dose. Only 36.1% of patients had any type of cardiac surveillance (echocardiography, BNP, or cardiac imaging) in the year following completion of anthracycline therapy (29.7% echocardiography). Surveillance rate increased from 37.5% in 2008 to 42.7% in 2018 (25.6% in 2008 to 40.5% echocardiography in 2018). Lymphoma patients had a lower likelihood of any surveillance compared with patients with breast cancer (odds ratio, 0.79 [95% CI, 0.74–0.85]; P <0.001). Patients with preexisting diagnoses of coronary artery disease and arrhythmia had the highest likelihood of cardiac surveillance (odds ratio, 1.54 [95% CI, 1.39–1.69] and odds ratio, 1.42 [95% CI, 1.3–1.53]; P <0.001 for both), although no single comorbidity was associated with a >50% rate of surveillance. Conclusions: The majority of survivors of breast cancer and lymphoma who have received anthracycline-based chemotherapy do not undergo cardiac surveillance after treatment, including those with a history of cardiovascular comorbidities, such as heart failure.

Background: Lymphoma patients exposed to chest RT during adolescence/young adulthood are at increased risk for BC; the cumulative incidence exceeds 20% by age 45 and the BC risk is comparable to that in women with BRCA1 mutations. These findings present an urgent yet unmet need to reduce the risk of BC in RT-exposed lymphoma survivors. The risk of BC is 50% lower in chest RT-exposed survivors who also receive ovarian radiation, suggesting a critical role of endogenous estrogens in RT-related breast carcinogenesis, making tamoxifen (a selective estrogen receptor modulator) an attractive risk-reducing option. Tamoxifen administered at 20 mg/d is effective in BC prevention in other high risk populations, but severe adverse events (SAE: venous thromboembolism, endometrial cancer) have limited its broad use. Previous biomarker trials in the general population have shown that LDTam (5mg/d) is not inferior to tamoxifen at 20 mg/d in reducing BC risk, and is associated with a safer AE profile. Mammographic breast density (MBD) is an established biomarker of BC risk; high MBD is associated with a 4-fold higher risk of BC. We hypothesized that LDTam would be effective in reducing BC risk (using MBD as a primary endpoint) in chest RT-exposed lymphoma survivors. We used an investigator-initiated, multi-institutional, randomized phase IIb, double blind, placebo controlled trial (FDA IND 107367) to test this hypothesis. Methods: Female patients from 13 sites were ≥25y at enrollment, with a history of exposure to chest RT at ≥12 Gy by age 40 for their primary cancer, and were off therapy for ≥6 mo. Subjects with a prior history of BC/DCIS, B/L mastectomy, or baseline MBD <25% in both breasts were excluded. Tamoxifen 5mg or identical placebo tablets were provided by Sharp Clinical Services (Allentown, PA) under good manufacturing practice. Subjects were randomized 1:1 in a double-blinded fashion by a Web-based system to receive LDTam or placebo daily for 2y. MBD (in both breasts) was measured centrally on digital scans independently by 3 radiologists at baseline, 1y and 2y. Using an intention-to-treat analysis, the efficacy of LDTam in reducing MBD was compared between the LDTam and placebo arms by applying a linear mixed effects model for bivariate normally distributed data with random intercept and time*treatment arm effects. Correlations between the left and right breasts and within radiologists were accounted for in the model. Treating clinicians and all research staff were blinded to the treatment arm. Results: A total of 72 patients (LDTam: n=34; placebo: n=38) participated in the trial; primary diagnosis: Hodgkin lymphoma (86%); non-Hodgkin lymphoma (10%); other (3%); median age at diagnosis of primary cancer: 21.5y (IQR, 16-28), and at trial enrollment: 43.8y (35-49); median time from diagnosis of primary cancer to study: 17.0y (12-26). Median chest RT dose: 30.3 Gy (21-37.3); 11% had received pelvic radiation; 39% were post-menopausal at study. Participant characteristics were comparable between the two treatment arms, as was the mean baseline MBD (LDTam: 52.6% vs. placebo: 50.4%, p=0.6). The time*treatment arm effect was statistically significant (LDTam vs. placebo: estimate = -1.7, SE = 0.5, p = 0.001), indicating a significantly lower mean fitted MBD for LDTam (43.9%) vs. placebo (47.3%) at 2y (Figure). This represented a 16.5% relative reduction in MBD on the LDTam arm, corresponding to an estimated 33% lower risk of BC (assuming that reductions in MBD have the same benefit in lymphoma survivors as they do in the general population). There were no grade 3 or 4 AEs related to LDTam. Grade 2 AEs did not differ between treatment arms (LDTam: 44.1% vs. placebo: 36.8%, p=0.6). There was no difference in the prevalence of moderate-to-severe patient-reported outcomes between the treatment arms (Table). Conclusion: Low-dose tamoxifen was associated with a significantly steeper decline in MBD in chest RT-exposed lymphoma survivors, when compared with placebo, and was safe and well-tolerated. This is the first trial demonstrating efficacy of a pharmacologic intervention in reducing a biomarker strongly associated with breast cancer risk in lymphoma survivors with a past history of chest radiation. Disclosures Palomares: Covance: Other: Medical monitoring. Henderson:Seattle Genetics: Research Funding. OffLabel Disclosure: The drug is a low-dose tamoxifen, a selective estrogen receptor modulator. Tamoxifen in standard doses is used to reduce the risk of breast cancer in high risk populations. Tamoxifen in standard or low doses have not been tested before for chest-irradiated cancer survivors to reduce the risk of radiation-related breast cancer.

Abstract Background Axillary web syndrome (AWS) can develop following breast cancer surgery and presents as a tight band of tissue in the axilla with shoulder abduction. Objective The objectives were to determine the prevalence and natural history of AWS and the association between AWS and function, range of motion, pain, lymphedema, and body mass index (BMI). Design This study was a longitudinal prospective cohort study utilizing a repeated measures design. Methods Axillary web syndrome, function, shoulder range of motion, pain, and lymphedema (using circumference, bioimpedance spectroscopy, tissue dielectric constant) were assessed in women at 2, 4, and 12 weeks and 18 months following breast cancer surgery. Prevalence of AWS and the association with the measured outcomes were analyzed. Results Thirty-six women agreed to participate in the study. The cumulative prevalence of AWS was 50% (18/36) at 18 months following breast cancer surgery. AWS was identified as a risk factor for reduced function. Women with AWS had statistically reduced range of motion, lower BMI, and higher number of lymph nodes removed compared to the non-AWS group. Forty-one percent (13/32) of women had AWS at 18 months. AWS reoccurred in 6 women following resolution, and a new case developed beyond the early postoperative period. The overall prevalence of physical impairments ranged from 66% to 97% within the first 18 months following surgery regardless of AWS. Limitations Limitations include a small sample size and potential treatment effect. Conclusion AWS occurs in approximately 50% of women following breast cancer surgery. It can persist for 18 months and potentially longer, develop beyond the early postoperative time period, and reoccur after resolution. Clinicians need to be aware of the chronicity of AWS and its association with reduced range of motion and function.

Background Axillary web syndrome (AWS) is a condition that may develop following breast cancer surgery and that presents as a palpable axillary cord of tissue. Objective The purposes of this study were: (1) to determine the clinical characteristics of AWS related to movement, function, pain, and postoperative edema and (2) to define the incidence of and risk factors for AWS within the first 3 months following breast cancer surgery. Design This was a prospective cohort study with a repeated-measures design. Methods Women who underwent breast cancer surgery with sentinel node biopsy or axillary lymph node dissection (N=36) were assessed for AWS, shoulder range of motion, function, pain, and postoperative edema (using girth measurements, bioimpedance, and tissue dielectric constant) at 2, 4, and 12 weeks. Demographic characteristics were used for risk analysis. Results Seventeen women (47.2%) developed AWS, and AWS persisted in 10 participants (27.8%) at 12 weeks. Abduction range of motion was significantly lower in the AWS group compared with the non-AWS group at 2 and 4 weeks. There were no differences between groups in measurements of function, pain, or edema at any time point. Trunk edema measured by dielectric constant was present in both groups, with an incidence of 55%. Multivariate analysis determined lower body mass index as being significantly associated with AWS (odds ratio=0.86; 95% confidence interval=0.74, 1.00). Limitations Limitations included a short follow-up time and a small sample size. Conclusion Axillary web syndrome is prevalent following breast/axilla surgery for early-stage breast cancer and may persist beyond 12 weeks. The early consequences include movement restriction, but the long-term effects of persistent AWS cords are yet unknown. Low body mass index is considered a risk factor for AWS.