Stuart M. Lichtman, MD, Guest Editor President, SIOG
As cancer therapies improve and the population as a whole increases, there are rising numbers of elderly patients with cancer. More than half of patients newly diagnosed with cancer are aged 65 years or older.1 In January 2012, it was estimated that more than 8 million cancer survivors were over age 65, comprising 59% of the prevalent population of cancer survivors.2 Concern for toxicity, particularly cardiac-related toxicity and treatment-related mortality, has led to lower-intensity regimens and impairments in outcomes in the aging population.
Impact of Aging
Aging cancer patients are particularly vulnerable to cardiotoxicity from cancer treatment because of their baseline risk resulting from their age.3 In general, older patients are affected by a number of factors, including concomitant comorbidities as well as other physiologic and functional changes that can affect prognosis, treatment, and outcomes of cancer.3,4 Approximately 20% of these patients also have underlying cardiovascular disease.
The presence of comorbidities can lead to polypharmacy and potential drug interactions with chemotherapy.5 Chemotherapy medications can result in direct cardiac injury. The sequential impact of these factors, previously described by Shenoy et al, can be conceptualized as a “snowball effect.” Baseline risks resulting from older age and age-related factors are “set into motion” by a cancer diagnosis, and then “momentum” is gained as cancer drugs cause direct injury on tissues or functional status is changed by the cancer.4 Ultimately, this leads to symptoms and a diagnosis of apparent cardiovascular manifestations.
Geriatrics for the Oncologist is guest edited by Stuart M. Lichtman, MD, and developed in collaboration with the International Society of Geriatric Oncology (SIOG). Dr. Lichtman is an Attending Physician at Memorial Sloan Kettering Cancer Center, Commack, New York, and Professor of Medicine at Weill Cornell Medical College, New York. He is also President of SIOG. For more information about geriatric oncology, visit www.siog.org and the new ASCO Geriatric Oncology website (www.asco.org/practice-guidelines/cancer-care-initiatives/geriatric-oncology/geriatric-oncology-resources).
Comprehensive Geriatric Assessment
In order to help care for the aging population with cancer, a multidimensional, interdisciplinary diagnostic process focusing on an older person’s medical, psychosocial, and functional capacity has been recommended.5 This coordinated care can be initiated with a comprehensive geriatric assessment.
While there are a number of tools available, the International Society of Geriatric Oncology has provided consensus guidelines recommending that the following domains be evaluated in a geriatric assessment: functional status; comorbidity; cognition; mental health status; fatigue; social status; nutrition; and the presence of geriatric syndromes defined as dementia, delirium, failure to thrive, incontinence, osteoporosis, or neglect/abuse, falls, constipation, polypharmacy, pressure ulcers, and sarcopenia.
Incorporating a geriatric assessment tool into the care of the geriatric cardio-oncology patient is important. The use of comprehensive geriatric assessments has been shown to improve overall survival, quality of life, and physical function, while decreasing hospitalizations and nursing home placement in the geriatric population.5
Cancer Treatment, Age, and Cardiac Complications
Given that the prevalence of coronary heart disease in the United States has been estimated at 18.6 million, occurring in 19.8% of people aged ≥ 65,6 the geriatric cancer population not only often has coronary heart disease at the time of diagnosis, but is also susceptible to cardiac injury from cancer treatment. Many cancer agents are known to cause cardiac toxicities, including anthracyclines, trastuzumab (Herceptin), tyrosine kinase inhibitors, and proteasome inhibitors.7 These cardiotoxic manifestations can include left-ventricular dysfunction and heart failure, myocardial ischemia and infarction, hypertension, and arrhythmias such as QT prolongation. Less frequently, these complications consist of myocarditis or pericarditis. Advancing age is a risk factor for cardiac toxicity from both anthracyclines and trastuzumab.7
There is a need for research on early biomarkers of toxicity as well as monitoring, surveillance, and treatment of older patients with cancer receiving potentially cardiotoxic therapy.— Anne H. Blaes, MD, MS
In a meta-analysis of over 10,000 patients, the overall incidence of all-grade and high-grade congestive heart failure associated with vascular endothelial growth factor receptor tyrosine kinase inhibitors was 3.2% (95% confidence interval [CI] = 1.8%–5.8%) and 1.4% (95% CI = 0.9%–2.3%), respectively.8 Age did not appear to be associated with increased risk; however, having a history of hyperlipidemia, heart failure, or known coronary artery disease was associated with an increased risk.9
Risk factors for chemotherapy-related cardiac complications should be assessed in all patients diagnosed with cancer who are being considered for cancer therapy, whether it be the administration of biologics, chemotherapy, or radiation therapy. Given that advancing age has been associated with cardiac complications from chemotherapy using anthracyclines or trastuzumab-based treatments, it is recommended that all elderly patients prescribed these medications should be educated about risk stratification and risk modification.7
These older patients should consult with a multidisciplinary team consisting of oncologists, cardiologists, primary care physicians, geriatricians, pharmacists, and nurses. Consideration for a cardio-oncology consultation should also occur in geriatric cancer patients with a cardiovascular history who are being prescribed tyrosine kinase inhibitors, chest radiation, proteasome inhibitors such as carfilzomib (Kyprolis), left-sided breast radiation, or combination systemic chemotherapy. The use of baseline cardiac magnetic resonance imaging or echocardiogram with strain imaging may be useful.
Collaborative assessment by oncologists and cardiologists before the start of chemotherapy can lead to early identification of patients at risk as well as discussions about the utility and benefits of cardiotoxic medications as opposed to potential alternative therapies. In some situations, alternative noncardiotoxic chemotherapy regimens may be considered. A lower-intensity chemotherapy regimen, however, should not be prescribed based simply on a patient’s risk factors or concern for potential cardiac complications, as this has been shown to potentially worsen clinical cancer outcomes.
Cardiologists should address the extent of baseline cardiac evaluation, the frequency of surveillance to detect cardiotoxicity, and the possible use of cardioprotective therapy such as beta-blockers and angiotensin-converting enzyme inhibitors for the primary prevention of cardiotoxicity. Guidelines can help to monitor geriatric patients receiving potentially cardiotoxic cancer treatments.10
There is a need for research on early biomarkers of toxicity as well as monitoring, surveillance, and treatment of older patients with cancer receiving potentially cardiotoxic therapy. The results of these studies are imperative in determining how best to risk-stratify and treat elderly patients with cancer while preserving their quality of life and functional outcomes. Increasing recruitment of older patients to cancer trials—by eliminating an upper age limit to clinical trial eligibility and mandating adequate representation of the elderly—is also important in determining how new therapies will impact our aging population. ■
Disclosure: Dr. Blaes reported no potential conflicts of interest.
8. Qi WX, Shen Z, Tang LN, et al: Congestive heart failure risk in cancer patients treated with vascular endothelial growth factor tyrosine kinase inhibitors: A systematic review and meta-analysis of 36 clinical trials. Br J Clin Pharmacol 78:748-762, 2014.
10. Zamorano JO, Lancellotti P, Munoz DR, et al: 2016 ESC position paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines. Eur Heart J 37:2768-2801, 2016.