Melissa K. Accordino

Cardiac Effects of Anticancer Therapy in the Elderly

Cancer incidence increases with age, and as life expectancy increases, the number of elderly patients with cancer is increasing. Cancer treatments, including chemotherapy and radiotherapy, have significant short- and long-term effects on cardiovascular function. These cardiotoxic effects can be acute, such as changes in electrocardiogram (ECG), arrhythmias, ischemia, and pericarditis and/or myocarditis-like syndromes, or they can be chronic, such as ventricular dysfunction. Anticancer therapies can also have indirect effects, such as alterations in blood pressure, or can cause metabolic abnormalities that subsequently increase risk for cardiac events. In this review, we explore both observational and clinical trial evidence of cardiac risk in the elderly. In both observational and clinical trial data, risk of cardiotoxicity with anthracycline-based chemotherapy increases with age. However, it is less clear whether the association between age and cardiotoxicity exists for newer treatments. The association may not be well demonstrated as a result of under-representation of elderly patients in clinical trials and avoidance of these therapies in this population. In addition, we discuss strategies for surveillance and prevention of cardiotoxicity in the elderly. In the elderly, it is important to be aware of the potential for cardiotoxicity during long-term follow-up and to consider both prevention and surveillance of these late effects.

Disparities and challenges in adherence to oral antineoplastic agents.

The issue of medication noncompliance is becoming increasingly important in oncology as more cancer therapies are delivered orally. Medication adherence is difficult to assess and there is no gold standard of measurement. The act of measuring adherence can affect outcomes. Medication noncompliance is common, and is estimated to be 50% in treatment of chronic diseases. Studies have shown that women initiate adjuvant hormonal therapy for breast cancer 64% to 88% of the time when prescribed. Of those who initiate therapy, 50% to 80% are adherent for the prescribed duration, depending on the study. Patients noncompliant with adjuvant hormonal therapy for breast cancer have worse overall survival than their counterparts. Suboptimal treatment responses in chronic myeloid leukemia (CML) are also associated with medication noncompliance. Poor adherence can also affect clinical trial results, leading to inaccuracies of treatment efficacy. Barriers to compliance can occur on the individual, cultural, or system level. Examples of specific barriers are side effects, cost and access to medication, and individual health beliefs. Specific populations, including racial minorities, elderly patients, and very young patients, may be at higher risk for medication noncompliance. Strategies to improve compliance are multifactorial and include improvement of patient education, reduction of treatment side effects, interventions to alter behavior, and changes in public policy to improve financial barriers to treatment. Technology has been an effective tool in improving compliance in noncancer-related illness, and ongoing studies are evaluating its role in the oncology population.

Nonadherence to Medications for Chronic Conditions and Nonadherence to Adjuvant Hormonal Therapy in Women With Breast Cancer

Importance While adjuvant hormonal therapy (HT) reduces mortality for women with nonmetastatic breast cancer, nonadherence to HT is common. Objective We investigated the association between patterns of prior nonadherence to medications for chronic conditions with HT nonadherence. Design, Setting, and Participants For this retrospective cohort study, the MarketScan database was scanned for women 18 years and older who had been diagnosed with nonmetastatic breast cancer between January 1, 2010, and December 31, 2012, and who filled 2 or more prescriptions for tamoxifen and/or an aromatase inhibitor. Main Exposures and Outcomes Nonadherence to medications for 6 chronic conditions (hypertension, hyperlipidemia, gastroesophageal reflux disease, thyroid disease, diabetes, osteoporosis) in the 12 months before diagnosis was defined as a medication possession ratio (MPR) less than 80%. Nonadherence to HT was defined as an MPR less than 80% between the first and last prescription for HT up to 2 years. Analysis Multivariable logistic regression was used to determine the association between prior medication nonadherence and HT nonadherence. Results Of 21 255 women treated with adjuvant HT, 3314 (15.6%) were nonadherent, and age (<55 or ≥75 years vs 55-64 years), higher 30-day out-of-pocket costs, and increased comorbidities were associated with nonadherence. Women without prior medications for 1 of the chronic conditions (n = 7828 [37%]) had an 18.4% nonadherence rate to HT. Those who used 1 or more medication prior to HT and were adherent (n = 9223 [43%]) had a 9.8% nonadherence rate to HT (relative to those without prior medications: odds ratio [OR] 0.56; 95% CI, 0.50-0.61), while those who were nonadherent to their chronic medications (n = 4214 [20%]) had a 23.1% nonadherence rate to HT (OR 1.43; 95% CI, 1.30-1.58). Adherence and nonadherence for medications for each of the 6 medical conditions was associated with adherence or nonadherence for HT, respectively. Conclusions and Relevance We found that nonadherence to medications for chronic conditions prior to HT was associated with greater nonadherence to oral HT in patients with breast cancer. Medication nonadherence history may play an important role in determining patients at risk for nonadherence to a subsequent medication for a different illness, such as HT, and a potential target for future interventions.

Trends in Use and Safety of Image-Guided Transthoracic Needle Biopsies in Patients With Cancer

PURPOSE Image-guided transthoracic needle biopsy (IGTTNB) is an important tool in the diagnosis of patients with cancer. Common complications include pneumothorax and chest tube placement, with rates ranging from 6% to 57%. We performed a population-based study to determine patterns of use, complications, and costs associated with IGTTNB. METHODS The Premier Perspective database was used to identify patients with cancer with ≥ one claim for IGTTNB from 2006 to 2012. Patients were stratified on the basis of inpatient versus outpatient setting. Pneumothorax was defined by a new claim within 1 month of IGTTNB; hospitalization and chest tube placement rates were analyzed. Multivariable analysis was used to identify factors associated with pneumothorax. RESULTS We Identified 79,518 patients with cancer who underwent IGTTNB: 42,955 (54.0%) outpatients and 36,563 (46.0%) inpatients. Of patients who underwent outpatient IGTTNB, 5,261 (12.2%) developed a pneumothorax. Of those, 1,006 (19.1%, 2.3% of total) were hospitalized, and 180 (3.4%, 0.42% of total) required chest tubes. Pneumothorax after outpatient IGTTNB was associated with number of comorbidities, rural site, hospital bed size of more than 600, and biopsy of parenchymal as opposed to pleural lesions. Of patients who underwent inpatient IGTTNB, 7,830 (21.4%) developed a pneumothorax, and 2,894 (36.0%, 7.9% of total) required chest tube. Over time, total IGTTNB volume increased by 40.6%, and mean outpatient cost per procedure increased by 24.4%. CONCLUSION While pneumothorax was frequent in outpatients, rates of hospitalization and chest tube placement were low. As screening for lung cancer increases, we anticipate an increased need for IGTNBB. Patients can be reassured by the low rate of serious complications.

Use and Costs of Disease Monitoring in Women With Metastatic Breast Cancer

PURPOSE The optimal frequency of monitoring patients with metastatic breast cancer (MBC) is unknown; however, data suggest that intensive monitoring does not improve outcomes. We performed a population-based analysis to evaluate patterns and predictors of extreme use of disease-monitoring tests (serum tumor markers [STMs] and radiographic imaging) among women with MBC. METHODS The SEER-Medicare database was used to identify women with MBC diagnosed from 2002 to 2011 who underwent disease monitoring. Billing dates of STMs (carcinoembryonic antigen and/or cancer antigen 15-3/cancer antigen 27.29) and imaging tests (computed tomography and/or positron emission tomography) were recorded; if more than one STM or imaging test were completed on the same day, they were counted once. We defined extreme use as > 12 STM and/or more than four radiographic imaging tests in a 12-month period. Multivariable analysis was used to identify factors associated with extreme use. In extreme users, total health care costs and end-of-life health care utilization were compared with the rest of the study population. RESULTS We identified 2,460 eligible patients. Of these, 924 (37.6%) were extreme users of disease-monitoring tests. Factors significantly associated with extreme use were hormone receptor-negative MBC (odds ratio [OR], 1.63; 95% CI, 1.27 to 2.08), history of a positron emission tomography scan (OR, 2.92; 95% CI, 2.40 to 3.55), and more frequent oncology office visits (OR, 3.14; 95% CI, 2.49 to 3.96). Medical costs per year were 59.2% higher in extreme users. Extreme users were more likely to use emergency department and hospice services at the end of life. CONCLUSION Despite an unknown clinical benefit, approximately one third of elderly women with MBC were extreme users of disease-monitoring tests. Higher use of disease-monitoring tests was associated with higher total health care costs. Efforts to understand the optimal frequency of monitoring are needed to inform clinical practice.

ReCAP: Serum Tumor Marker Use in Patients With Advanced Solid Tumors

PURPOSE There is substantial variability in the frequency of serum tumor marker testing in patients with advanced solid tumors. We performed a retrospective analysis to evaluate the frequency of serum tumor marker use. METHODS Patients with a diagnosis of advanced cancer with outpatient visits between July 1, 2013, and June 30, 2014, at a single center were included. Tumor and stage were determined by International Classification of Diseases, Ninth Revision codes and confirmed with tumor registry and medical record review. For each patient, we recorded the dates of each of the following tumor markers: a-fetoprotein, CA-125, CA 15-3, CA 19-9, CA 27-29, and carcinoembryonic antigen. We evaluated the number of tests per patient over 12 months and the maximum number of tests per patient per month. RESULTS We included 928 patients in the analysis. The mean number of any individual test per patient was seven tests, and the maximum number was 35 tests; the mean number of total tests per patient was 12 tests, and the maximum number was 70 tests; 16.3% of patients had more than 12 individual tests per year. In a 1-month span, 34.3% of patients had more than one individual test. CA 19-9 and carcinoembryonic antigen were the most commonly overused tests. CONCLUSION We found a high rate of serum tumor marker testing use in patients with advanced solid tumors. Given the increasing costs of cancer care, efforts should be made to determine the benefit of serum tumor markers in the follow-up care of patients with advanced solid tumors.

Nonadherence to Oral Medications for Chronic Conditions in Breast Cancer Survivors

PURPOSE Nonadherence to oral endocrine therapy is common among women with breast cancer (BC). Less is known about nonadherence to medications for other chronic conditions among survivors of BC. METHODS We used the MarketScan Database to identify women older than 18 years who had nonmetastatic BC diagnosed between January 1, 2009, and December 31, 2013. Prescriptions were identified for the following six non-cancer-related conditions: hypertension, thyroid disease, hyperlipidemia, gastroesophageal reflux disease, diabetes, and osteoporosis. The study period was defined as 1 year before BC diagnosis (index date) through 1.5 years after the index date, with a 6-month washout period after the index data to control for adherence during the preoperative period and during chemotherapy if necessary. Adherence was defined as a medication possession ratio ≥ 80%. Change in adherence was defined as a 20% decrease in the medication possession ratio from the time before diagnosis compared with after treatment. Factors associated with change in adherence were evaluated in multivariable logistic models. RESULTS Among 36,149 patients diagnosed with BC, the average adherence to these medications before BC was 91.4%. However, after BC treatment, adherence decreased to 77.9% (P < .001). Looking at drugs for each condition, nonadherence ranged from 15.6% to 38% (P < .001). Factors associated with an increase in nonadherence included older age, insurance type, number of medications, and comorbid conditions. CONCLUSION Decreased adherence to medications for chronic diseases was found in the first year after breast cancer treatment. Breast cancer survivors may need additional interventions to improve their adherence to their medications for chronic conditions.

Safety, Utilization, and Cost of Image-Guided Percutaneous Liver Biopsy Among Cancer Patients

Abstract Image-guided percutaneous liver biopsy (PLB) is a diagnostic tool for lesions in the liver. Hemorrhage is the most common complication. We selected patients with a diagnostic claim for cancer who had undergone PLB. There were a total of 26,941 patients who underwent PLB. Hemorrhage risk was 1.43% among patients undergoing PLB. When stratified by setting, odds of hemorrhage were 4.5 times higher when biopsy was performed in an inpatient setting (p < .001). Risk factors associated with hemorrhage included marital status, liver cancer and comorbidity score. The use of PLB has increased over time. Reassuringly, the hemorrhage risk associated with PLB is low.

Utilization of gynecologic services in women with breast cancer receiving hormonal therapy

BACKGROUND: The selective estrogen receptor modulator tamoxifen is now widely used for the treatment and prevention of breast cancer. Tamoxifen use has been associated with a variety of gynecologic problems. Despite the frequency with which hormonal therapy is used for the treatment of breast cancer, limited population‐level data are available to describe the occurrence of gynecologic conditions and the use of surveillance testing in women receiving tamoxifen and aromatase inhibitors. OBJECTIVE: We performed a population‐based analysis among women with breast cancer receiving hormonal therapy with tamoxifen, a drug commonly used in premenopausal and sometimes postmenopausal women, to determine the frequency of gynecologic abnormalities and use of diagnostic and surveillance testing. We compared these findings to women treated with aromatase inhibitors, agents commonly used in postmenopausal women. STUDY DESIGN: The MarketScan database was used to identify women diagnosed with breast cancer from 2009 through 2013 who underwent mastectomy or lumpectomy. Women receiving tamoxifen (age <50 vs ≥50 years) were compared to women ≥50 years of age treated with aromatase inhibitors. We examined the occurrence of gynecologic symptoms and diseases (vaginal bleeding, endometrial polyps, endometrial hyperplasia, and endometrial cancer) and gynecologic procedures and interventions (transvaginal ultrasound, endometrial biopsy, hysteroscopy/dilation and curettage, and hysterectomy). Time‐dependent analyses were performed to examine symptoms and testing. RESULTS: A total of 75,170 women, including 15,735 (20.9%) age <50 years treated with tamoxifen, 13,827 (18.4%) age ≥50 years treated with tamoxifen, and 45,608 (60.7%) age ≥50 years treated with aromatase inhibitors were identified. The cumulative incidence of any gynecologic symptom or pathologic diagnosis during the study period was 20.2%, 12.3%, and 3.5%, respectively (P < .001), while the cumulative incidence of any gynecologic procedure or intervention during the study period was 34.2%, 20.9%, and 9.0%, respectively (P < .0001). Among women without symptoms or pathology, interventions were performed in 20.0%, 11.0%, and 6.8%, respectively (P < .0001). CONCLUSION: Compared to women taking aromatase inhibitors, gynecologic symptoms, procedures, and pathology are higher for both premenopausal and postmenopausal women with breast cancer on tamoxifen. Increased efforts to curb use of gynecologic interventions in asymptomatic women are needed.

Trends in end-of-life care and health care spending in women with uterine cancer

BACKGROUND: High‐intensity care including hospitalizations, chemotherapy, and other interventions at the end of life is costly and often of little value for cancer patients. Little is known about patterns of end‐of‐life care and resource utilization for women with uterine cancer. OBJECTIVE: We examined the costs and predictors of aggressive end‐of‐life care for women with uterine cancer. STUDY DESIGN: In this observational cohort study the Surveillance, Epidemiology, and End Results‐Medicare linked database was used to identify women age ≥65 years who died from uterine cancer from 2000 through 2011. Resource utilization in the last month of life including ≥2 hospital admissions, >1 emergency department visit, ≥1 intensive care unit admission, or use of chemotherapy in the last 14 days of life was examined. High‐intensity care was defined as the occurrence of any of the above outcomes. Logistic regression models were developed to identify factors associated with high‐intensity care. Total Medicare expenditures in the last month of life are reported. RESULTS: Of the 5873 patients identified, the majority had stage IV cancer (30.2%), were white (79.9%), and had endometrioid tumors (47.6%). High‐intensity care was rendered to 42.5% of women. During the last month of life, 15.0% had ≥2 hospital admissions, 9.0% had a hospitalization >14 days, 15.3% had >1 emergency department visits, 18.3% had an intensive care unit admission, and 6.6% received chemotherapy in the last 14 days of life. The percentage of women who received high‐intensity care was stable over the study period. Characteristics of younger age, black race, higher number of comorbidities, stage IV disease, residence in the eastern United States, and more recent diagnosis were associated with high‐intensity care. The median Medicare payment during the last month of life was