Jeffrey Sulpher

Canadian Cardiovascular Society Guidelines for Evaluation and Management of Cardiovascular Complications of Cancer Therapy

Modern treatment strategies have led to improvements in cancer survival, however, these gains might be offset by the potential negative effect of cancer therapy on cardiovascular health. Cardiotoxicity is now recognized as a leading cause of long-term morbidity and mortality among cancer survivors. This guideline, authored by a pan-Canadian expert group of health care providers and commissioned by the Canadian Cardiovascular Society, is intended to guide the care of cancer patients with established cardiovascular disease or those at risk of experiencing toxicities related to cancer treatment. It includes recommendations and important management considerations with a focus on 4 main areas: identification of the high-risk population for cardiotoxicity, detection and prevention of cardiotoxicity, treatment of cardiotoxicity, and a multidisciplinary approach to cardio-oncology. All recommendations align with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Key recommendations for which the panel provides a strong level of evidence include: (1) that routine evaluation of traditional cardiovascular risk factors and optimal treatment of preexisting cardiovascular disease be performed in all patients before, during, and after receiving cancer therapy; (2) that initiation, maintenance, and/or augmentation of antihypertensive therapy be instituted per the Canadian Hypertension Educational Program guidelines for patients with preexisting hypertension or for those who experience hypertension related to cancer therapy; and (3) that investigation and management follow current Canadian Cardiovascular Society heart failure guidelines for cancer patients who develop clinical heart failure or an asymptomatic decline in left ventricular ejection fraction during or after cancer treatment. This guideline provides guidance to clinicians on contemporary best practices for the cardiovascular care of cancer patients.

Shared Risk Factors for Cardiovascular Disease and Cancer: Implications for Preventive Health and Clinical Care in Oncology Patients

The cardiovascular toxicity of cancer therapy has raised awareness of the importance of heart disease in cancer care among oncologists and cardiologists, leading to the new interdisciplinary field of cardio-oncology. Evidence is accumulating to suggest that risk factors associated with cardiovascular disease are also related to an increased incidence of cancer and excess cancer mortality. We review the epidemiologic evidence that smoking, obesity, poor diet, and inactivity can cause both heart disease and cancer. The importance of cardiovascular disease and cardiovascular risk factors in adversely affecting oncological outcomes and leading to increased cancer mortality is discussed. Cardiotoxicity prediction tools that incorporate cardiac disease and risk factors are described. Raising awareness about shared risk factors for cancer and heart disease may result in more effective advocacy to promote healthy lifestyle changes through the combined efforts of the historically separate specialties of cardiology and oncology.

An International Survey of Health Care Providers Involved in the Management of Cancer Patients Exposed to Cardiotoxic Therapy.

Cardiotoxicity is the second leading cause of morbidity and mortality in cancer survivors. The objective of this international cardiac oncology survey was to gain a better understanding of current knowledge and practice patterns among HCPs involved in the management of cancer patients exposed to potentially cardiotoxic drugs. Between 2012 and 2013, we conducted an email-based survey of HCPs involved in the management of cardiac disease in cancer patients. 393 survey responses were received, of which 77 were from Canadian respondents. The majority of respondents were cardiologists (47%), followed closely by medical oncologists. The majority of respondents agreed that cardiac issues are important to cancer patients (97%). However, only 36% of total respondents agreed with an accepted definition of cardiotoxicity. While 78% of respondents felt that cardiac medications are protective during active cancer treatment, only 51% would consider prescribing these medications up-front in cancer patients. Although results confirm a high level of concern for cardiac safety, there continues to be a lack of consensus on the definition of cardiotoxicity and a discrepancy in clinical practice between cardiologists and oncologists. These differences in opinion require resolution through more effective research collaboration and formulation of evidence-based guidelines.

Right heart function deteriorates in breast cancer patients undergoing anthracycline-based chemotherapy

Background Cardiotoxicity from anthracycline-based chemotherapy is an important cause of early and late morbidity and mortality in breast cancer patients. Left ventricular (LV) function is assessed for patients receiving anthracycline-based chemotherapy to identify cardiotoxicity. However, animal studies suggest that right ventricular (RV) function may be a more sensitive measure to detect LV dysfunction. The purpose of this pilot study was to determine if breast cancer patients undergoing anthracycline-based chemotherapy experience RV dysfunction. Methods Forty-nine breast cancer patients undergoing anthracycline-based chemotherapy at the Ottawa Hospital between November 2007 and March 2013 and who had 2 echocardiograms performed at least 3months apart were retrospectively identified. Right atrial area (RAA), right ventricular fractional area change (RV FAC) and RV longitudinal strain of the free wall (RV LSFW) were evaluated according to the American Society of Echocardiography guidelines. Results The majority (48/49) of patients were females with an average age of 53.4 (95% CI: 50.1–56.7years). From baseline to follow-up study, average LV ejection fraction (LVEF) decreased from 62.22 (95% CI: 59.1–65.4) to 57.4% (95% CI: 54.0–60.9) (P=0.04). During the same time period, the mean RAA increased from 12.1cm2 (95% CI: 11.1–13.0cm2) to 13.8cm2 (95% CI: 12.7–14.9cm2) (P=0.02), mean RV FAC decreased (P=0.01) from 48.3% (95% CI: 44.8–51.74) to 42.1% (95% CI: 38.5–45.6%), and mean RV LSFW worsened from −16.2% (95% CI: −18.1 to −14.4%) to −13.81% (95% CI: −15.1 to −12.5%) (P=0.04). Conclusion This study demonstrates that breast cancer patients receiving anthracycline-based chemotherapy experience adverse effects on both right atrial size and RV function. Further studies are required to determine the impact of these adverse effects on right heart function and whether this represents an earlier marker of cardiotoxicity.

Clinical Experience of Patients Referred to a Multidisciplinary Cardiac Oncology Clinic: An Observational Study

Cardiotoxicity is the second leading cause of long-term morbidity and mortality among cancer survivors. The purpose of this retrospective observational study is to report on the clinical and cardiac outcomes in patients with early stage and advanced cancer who were referred to our multidisciplinary cardiac oncology clinic (COC). A total of 428 patients were referred to the COC between October 2008 and January 2013. The median age of patients at time of cancer diagnosis was 60. Almost half of patients who received cancer therapy received first-line chemotherapy alone (169, 41.7%), of which 84 (49.7%) were exposed to anthracyclines. The most common reasons for referral to the cardiac oncology clinic were decreased LVEF (34.6%), prechemotherapy assessment (11.9%), and arrhythmia (8.4%). A total of 175 (40.9%) patients referred to the COC were treated with cardiac medications. The majority (331, 77.3%) of patients were alive as of January 2013, and 93 (21.7%) patients were deceased. Through regular review of cardiac oncology clinic referral patterns, management plans, and patient outcomes, we aim to continuously improve delivery of cardiac care to our patient population and optimize cardiac health.

Factors influencing a specific pathologic diagnosis of non-small-cell lung carcinoma.

INTRODUCTION Historically, a non-small-cell lung carcinoma diagnosis, without pathologic subclassification, provided sufficient information to guide therapy. Evidence now demonstrates that pathologic subtype classification is central in selecting optimal treatment. This review aimed to identify factors associated with a specific pathologic diagnosis. METHODS All nonoperative cases of non-small-cell lung carcinoma (NSCLC) referred to the medical oncology divisions of the Ottawa Hospital Cancer Centre (2008) and Princess Margaret Hospital, Toronto (2007-2010) were identified. The charts were reviewed for demographics, diagnostic methods, and final diagnosis. Logistic regression was performed to identify variables associated with a specific diagnosis. RESULTS Of 739 patient records analyzed, 377 (51%) were men, 299 (40%) were aged over 70 years, and 510 (69%) had an Eastern Cooperative Oncology Group performance status of 0-2. Three hundred and eighty five (52%) of patients were diagnosed in a tertiary academic center. The lung primary was sampled in 503 (68%) of patients. Computed tomography-guided biopsy (n = 370, 50%) and bronchoscopy (n = 179, 24%) were the most common techniques. Four hundred and seventy seven (65%) of biopsies were cytologic specimens alone, and immunohistochemistry was performed in 337 (46%) of cases. The most common diagnoses were adenocarcinoma (n = 338, 46%), NSCLC not otherwise specified (n = 254, 34%), and squamous cell carcinoma (n = 115, 16%). Overall, 456 (62%) of patients received a specific pathologic diagnosis. Factors significantly associated with attaining a specific pathologic diagnosis were diagnosis outside an academic center (adjusted odds ratios [OR] 2.1 [95% CI, 1.41-3.14]; P = .0003), histologic laboratory samples (adjusted OR 1.58 [95% CI, 1.003-2.49]; P = .049), and immunohistochemical testing (adjusted OR 1.82 [95% CI, 1.25-2.70], P = .0021). CONCLUSIONS A significant minority of patients with NSCLC do not receive a specific pathologic diagnosis. In an era of individualized medicine, this may potentially impact optimal clinical management.

Evaluation, prevention and management of cancer therapy-induced cardiotoxicity: a contemporary approach for clinicians.

Purpose of review While targeted therapies have improved cancer outcomes, unique cardiovascular toxicities are increasingly recognized, particularly when administered sequentially after anthracyclines or radiation. Patients with cancer therapy-induced cardiotoxicity benefit from collaborative care involving cardiology and oncology, leading to a new interdisciplinary field called cardio-oncology. The present review will highlight contemporary clinical issues in cardio-oncology. Recent findings Recently, risk factors for cancer therapy-induced cardiotoxicity have been evaluated in real-world rather than in clinical trial patients. Biomarkers and advanced echocardiography are emerging as sensitive tools for preclinical identification of cancer therapy-induced cardiotoxicity. Single-center studies suggest that cancer therapy-induced cardiotoxicity responds to prompt heart failure medical treatment, and such therapy may even prevent cardiotoxicity. Summary Modern cancer therapy has short-term cardiac risk that may require collaborative management by clinicians with expertise in cardiology and oncology. The increased effectiveness of modern cancer therapy is resulting in a growing population of cancer survivors who are at long-term risk for cardiovascular disease. The present review of contemporary clinical issues in cardio-oncology will be of interest to healthcare providers who manage cardiotoxicity during cancer therapy, and who follow patients who survive cancer but face increased long-term cardiovascular risk.

Neoadjuvant chemotherapy in breast cancer: what questions remain?

Purpose of reviewAlthough neoadjuvant therapy (NAT) has become a popular approach in the systemic management of breast cancer, several important clinical questions remain unanswered. In this article, we review the literature pertaining to these questions and discuss the management strategies based on our findings. Recent findingsCurrently, the optimal duration of NAT is unclear. At this time, there is no compelling data to support the extension of traditional neoadjuvant chemotherapy regimens. In patients with triple-negative breast cancer, pathologic complete response may be prognostic and the appropriate use of neoadjuvant chemotherapy is crucial to achieve improved survival. In human epidermal growth factor receptor 2 (HER2)-positive disease, it is reasonable to consider dual blockade with trastuzumab and pertuzumab in combination with a taxane in the neoadjuvant setting. Finally, there is currently no evidence to support the use of further adjuvant chemotherapy in those patients with residual disease after NAT. SummaryThere remain many unanswered questions with the use of neoadjuvant chemotherapy in breast cancer, and further randomized clinical trials are needed. The results of these trials will permit the clinicians to develop ‘personalized’ treatment approaches, thus giving women the best chance of survival.

Acute Cardiogenic Shock Induced by Infusional 5-Fluorouracil

A 49-year-old patient with metastatic carcinoma of the bladder and no prior history of heart disease presented with diffuse ST elevation, elevated troponins, and biventricular dysfunction requiring intensive care unit admission and inotropic support after receiving her first course of infusional 5-fluorouracil (5-FU). Over the course of several days, the patients cardiac function and clinical status returned to baseline. A follow-up echocardiogram performed 5 days after initial presentation revealed an ejection fraction of 59 percent, with no evidence of wall motion abnormalities. Subsequent 5-FU chemotherapy was discontinued, and the patient went on to receive second-line chemotherapy.

Screening and Monitoring for Cardiotoxicity During Cancer Treatment

Cardiovascular disease and cancer lead to significant morbidity and mortality in the North American population. Improvements in cancer therapies have led to increased survivorship; however, these treatments may contribute to cardiovascular morbidity and mortality that threaten to undermine cancer-specific survival gains. The new subspecialty of “cardio-oncology” aims to keep pace with the rapid evolution of cancer therapies and the incidence, magnitude, and consequences of their cardiovascular side effects (i.e., cardiotoxicity). Currently, guidance on the optimal cardiovascular surveillance of cancer patients during and following cancer treatments is lacking. Traditional markers to detect cardiotoxicity, such as resting LVEF by echocardiography or MUGA, are likely insensitive for early cardiovascular injury. Alternative techniques have been proposed including advanced cardiac imaging modalities such as cardiac MRI or strain imaging by echocardiography, functional capacity testing, blood-based biomarkers, and genetic testing, but no best approach or combination of approaches has clearly emerged. Research evaluating the role of these alternative techniques as well as their optimal timing and frequency for cardiovascular surveillance in cancer is currently limited. Large prospective, multi-institutional studies are needed to determine whether these techniques can be used practically to improve not only detection of cardiotoxicity but also prediction of cardiovascular and overall survival. These data may, in turn, inform the use of early interventions to reduce the risk of downstream cardiovascular morbidity without compromising the efficacy of cancer therapies.