Cynthia Owusu

Predicting Chemotherapy Toxicity in Older Adults With Cancer: A Prospective Multicenter Study

PURPOSE Older adults are vulnerable to chemotherapy toxicity; however, there are limited data to identify those at risk. The goals of this study are to identify risk factors for chemotherapy toxicity in older adults and develop a risk stratification schema for chemotherapy toxicity. PATIENTS AND METHODS Patients age ≥ 65 years with cancer from seven institutions completed a prechemotherapy assessment that captured sociodemographics, tumor/treatment variables, laboratory test results, and geriatric assessment variables (function, comorbidity, cognition, psychological state, social activity/support, and nutritional status). Patients were followed through the chemotherapy course to capture grade 3 (severe), grade 4 (life-threatening or disabling), and grade 5 (death) as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events. RESULTS In total, 500 patients with a mean age of 73 years (range, 65 to 91 years) with stage I to IV lung (29%), GI (27%), gynecologic (17%), breast (11%), genitourinary (10%), or other (6%) cancer joined this prospective study. Grade 3 to 5 toxicity occurred in 53% of the patients (39% grade 3, 12% grade 4, 2% grade 5). A predictive model for grade 3 to 5 toxicity was developed that consisted of geriatric assessment variables, laboratory test values, and patient, tumor, and treatment characteristics. A scoring system in which the median risk score was 7 (range, 0 to 19) and risk stratification schema (risk score: percent incidence of grade 3 to 5 toxicity) identified older adults at low (0 to 5 points; 30%), intermediate (6 to 9 points; 52%), or high risk (10 to 19 points; 83%) of chemotherapy toxicity (P < .001). CONCLUSION A risk stratification schema can establish the risk of chemotherapy toxicity in older adults. Geriatric assessment variables independently predicted the risk of toxicity.

Predictors of Tamoxifen Discontinuation Among Older Women With Estrogen Receptor–Positive Breast Cancer

PURPOSE Five years of adjuvant tamoxifen therapy for estrogen receptor (ER) -positive breast cancer is more effective than 2 years of use. However, information on tamoxifen discontinuation is scanty. We sought to identify predictors of tamoxifen discontinuation among older women with breast cancer. PATIENTS AND METHODS Within six health care delivery systems, we identified women >or= 65 years old diagnosed with stage I to IIB ER-positive or indeterminant breast cancer between 1990 and 1994 who had filled a prescription for adjuvant tamoxifen. We observed them for 5 years after initial tamoxifen prescription. We used automated pharmacy records to validate tamoxifen prescription information abstracted from medical records. The primary end point was tamoxifen discontinuation, operationalized as ever discontinuing tamoxifen during 5 years of follow-up. We used Cox proportional hazards to identify predictors of tamoxifen discontinuation. RESULTS Of 961 women who were prescribed tamoxifen, 49% discontinued tamoxifen before the completion of 5 years. Discontinuers were more likely to be aged 75 to less than 80 years (v < 70 years; hazard ratio [HR] = 1.41; 95% CI, 1.06 to 1.87), be aged >or= 80 years (HR = 2.02; 95% CI, 1.53 to 2.66), have an increase in Charlson Comorbidity Index at 3 years from diagnosis (HR = 1.52; 95% CI, 1.18 to 1.95), have an increase in the number of cardiopulmonary comorbidities at 3 years (HR = 1.75; 95% CI, 1.34 to 2.28), have indeterminant ER status (v ER-positive status; HR = 1.36; 95% CI, 1.00 to 1.85), and have received breast-conserving surgery (BCS) without radiotherapy (v mastectomy; HR = 1.62; 95% CI, 1.18 to 2.22). CONCLUSION Attention to nonadherence among older women at risk of discontinuation, particularly those receiving BCS without radiotherapy, might improve breast cancer outcomes for these women.

Incidence of Heart Failure or Cardiomyopathy After Adjuvant Trastuzumab Therapy for Breast Cancer

OBJECTIVES The purpose of this study was to estimate heart failure (HF) and cardiomyopathy (CM) rates after adjuvant trastuzumab therapy and chemotherapy in a population of older women with early-stage breast cancer. BACKGROUND Newer biologic therapies for breast cancer such as trastuzumab have been reported to increase HF and CM in clinical trials, especially in combination with anthracycline chemotherapy. Elderly patients, however, typically have a higher prevalence of cardiovascular risk factors and have been underrepresented in trastuzumab clinical trials. METHODS Using Surveillance, Epidemiology, and End Results-Medicare data from 2000 through 2007, we identified women 67 to 94 years of age with early-stage breast cancer. We calculated 3-year incidence rates of HF or CM for the following mutually exclusive treatment groups: trastuzumab (with or without nonanthracycline chemotherapy), anthracycline plus trastuzumab, anthracycline (without trastuzumab and with or without nonanthracycline chemotherapy), other nonanthracycline chemotherapy, or no adjuvant chemotherapy or trastuzumab therapy. HF or CM events were ascertained from administrative Medicare claims. Poisson regression was used to quantify risk of HF or CM, adjusting for sociodemographic factors, cancer characteristics, and cardiovascular conditions. RESULTS We identified 45,537 older women (mean age: 76.2 years, standard deviation: 6.2 years) with early-stage breast cancer. Adjusted 3-year HF or CM incidence rates were higher for patients receiving trastuzumab (32.1 per 100 patients) and anthracycline plus trastuzumab (41.9 per 100 patients) compared with no adjuvant therapy (18.1 per 100 patients, p < 0.001). Adding trastuzumab to anthracycline therapy added 12.1, 17.9, and 21.7 HF or CM events per 100 patients over 1, 2, and 3 years of follow-up, respectively. CONCLUSIONS HF or CM are common complications after trastuzumab therapy for older women, with higher rates than those reported from clinical trials.

Polypharmacy and Potentially Inappropriate Medication Use in Older Adults with Cancer Undergoing Chemotherapy: Effect on Chemotherapy‐Related Toxicity and Hospitalization During Treatment

To evaluate the prevalence of polypharmacy and potentially inappropriate medication (PIM) use and the association between these and chemotherapy‐related adverse events in older adults with cancer undergoing chemotherapy.

Comorbidities, Functional Limitations, and Geriatric Syndromes in Relation to Treatment and Survival Patterns Among Elders With Colorectal Cancer

PURPOSE To examine patterns of colorectal cancer (CRC) treatment and survival in relation to comorbidities (COM), functional limitations (FL), and geriatric syndromes (GS). METHODS Our study population consisted of Ohio elders diagnosed with incident invasive CRC in the period August 1999 to November 2001 and admitted to home health care (HHC) in the 30 days before or after cancer diagnosis (n = 1009). We used data from the Ohio Cancer Incidence Surveillance System, vital records, and Medicare administrative data, including the HHC Outcome and Assessment Information Set (OASIS), which includes detailed clinical data for HHC patients. Counts of COM, FL, and GS at baseline were retrieved from the OASIS. Multivariable logistic and survival models were developed to examine the association between clinical attributes and outcomes, adjusting for demographic covariates and cancer stage. RESULTS Comorbidities were associated with increased likelihood of surgery-only, but not with surgery + chemotherapy. Both FL and GS were associated with lower likelihood to undergo surgery-only or surgery + chemotherapy. Two or more GS was associated with disease-specific mortality (adjusted hazard ratio [AHR]: 2.71; 95% confidence interval [CI]: 1.80-4.07) and overall mortality (AHR: 2.34; 95% CI: 1.74-3.15). Two or more FL was associated with overall mortality (AHR: 1.33; 95% CI: 1.10-1.62), but not with disease-specific mortality. COM was not associated with overall mortality, but was negatively associated with disease-specific mortality at borderline level of significance (AHR: 0.78; 95% CI: 0.61-1.00). CONCLUSION Our findings demonstrate the importance of accounting for FL and GS, in addition to COM, when studying cancer-related outcomes in elders.

Referral, Receipt, and Completion of Chemotherapy in Patients With Early-Stage Breast Cancer Older Than 65 Years and at High Risk of Breast Cancer Recurrence

PURPOSE Some women with early-stage breast cancer are at higher risk of recurrence and can benefit from chemotherapy. We describe patterns of referral, receipt, and completion of chemotherapy among older women at high risk of recurrence. PATIENTS AND METHODS A total of 2,124 women age 65 years or older who were diagnosed with early-stage breast cancer between 1990 and 1994 and 1996 to 1999 were included; 1,090 of these were at high risk of recurrence. We reviewed medical records to categorize chemotherapy outcomes as follows: did not discuss or were not referred to a medical oncologist (n = 133); discussed and/or referred to a medical oncologist but received no chemotherapy (n = 742); received an incomplete chemotherapy course (n = 29), or received a completed chemotherapy course (n = 186). RESULTS Overall, 19.7% of high-risk women received any chemotherapy, and 86.5% of these women completed their chemotherapy courses. Just greater than 10% of high-risk women did not have a discussion about chemotherapy as part of breast cancer treatment documented in the medical record; these women also received fewer diagnostic assessments of their initial tumors. CONCLUSION Individuals who receive chemotherapy for early-stage breast cancer are a select subgroup of patients at high risk of recurrence. This study identifies characteristics of women who were referred for and who received chemotherapy, and this study plays an important role in understanding generalizability of studies that examine chemotherapy treatment effectiveness. Outcomes after breast cancer could continue to be improved with increased receipt of chemotherapy among older women at high risk of breast cancer recurrence.

The relationship between age, anxiety, and depression in older adults with cancer.

In older men with prostate cancer, aging is associated with reduced anxiety and increased depression. The purpose of this study was to examine the association among age, anxiety, and depression in a cohort of older adults receiving chemotherapy.

Mentoring junior faculty in geriatric oncology: report from the Cancer and Aging Research Group.

Approximately 60% of cancer incidence, and 70% of cancer mortality, occurs in older adults.1 Unfortunately, cancer care is hampered by a lack of data regarding the risks and benefits of cancer therapy in older adults.2-5 Older adults have been underrepresented on clinical trials, and geriatric issues traditionally have not been considered in oncology study design. The need for evidence-based recommendations for healthy and vulnerable or frail older adults is critical, as life expectancy increases and aging baby boomers are expected to double the US population that is aged 65 years and older by 2030.6 The challenge imminently facing the field of medical oncology is that there are not enough oncologists or geriatricians available today to care for this growing population of older adults with cancer. Further, there is little crosstalk between these fields that would lead to the development and design of pertinent research studies. To bridge this gap, the American Society of Clinical Oncology and the John A. Hartford Foundation supported 10 training programs in geriatrics and oncology from 2001 to 2006. Twenty-eight geriatric oncology trainees participated in the combined fellowship program at these institutions. Several other individuals have trained sequentially in geriatrics and oncology or have developed a research interest in the field of geriatric oncology. These investigators are now entering junior faculty positions. Their training provides them with the skills to design and develop research in the field of geriatric oncology and to forge collaborations with internal medicine, geriatrics, and oncology. These new researchers are positioned not only to conduct research studies regarding the questions that are crucial to geriatric oncology, but also to promote the enrollment of older adults in cancer clinical trials. However, the progress of these young investigators who are working at the intersection of geriatrics and oncology may be hampered for several reasons. First, because of the multidisciplinary nature of their work, it may be difficult for them to find mentors at their own institutions who share their interest in the older patient with cancer. Second, the investigators are geographically dispersed. Multisite collaborations represent a challenge for all investigative teams, but this is particularly so for those new to an underrepresented field in cancer research. Third, many academic medical centers tend to attract a relatively young patient population. This can make it more difficult to perform geriatric oncology studies and expeditiously meet the accrual goal of older patients at a single institution. In aggregate, these barriers may limit the ability of these uniquely trained individuals to obtain grant funding and to develop and to accrue patients on to interdisciplinary clinical trials that evaluate and treat older patients with malignancies. Presently, there is no direct mechanism for junior faculty in geriatric oncology to develop collaborations and mentoring relationships with others in the field. To address this need, junior investigators in geriatric oncology and a senior mentoring team assembled in Duarte, California, in April 2007 for the first Cancer and Aging Research Group Meeting. The meeting was collaboratively supported by the John A. Hartford Foundation and the City of Hope. The goals of this meeting were to do the following three things: provide feedback on geriatric oncology research proposals, discuss approaches to obtain funding for geriatric oncology research, and encourage collaboration/networking among junior faculty in geriatric oncology. Two days of discussion generated and fine-tuned clinical research proposals that were considered high priority in geriatric oncology. At the meeting, the junior investigators presented concepts and ongoing geriatric oncology research for critique by both their peers and senior mentors. In addition, collaborative ties were developed among junior and senior investigators with similar research interests. Three critical areas of research in geriatric oncology were deemed high priority by both junior and senior investigators. These include the assessment of physiologic age, pharmacology of cancer therapy in older adults, and cancer survivorship issues pertinent to older adults. At the end of the conference, several practical recommendations for clinical trial design emerged. The consensus of the Cancer and Aging Research Group was that a geriatric assessment, as an assessment of physiologic age, should be included in all clinical trials that involve patients aged 70 years and older. Incorporating a geriatric assessment in clinical trials of older adults can strengthen the clinical trial design in the following ways: A geriatric assessment captures competing causes of morbidity and mortality, which can be accounted for in the data analysis7-17; a geriatric assessment would identify factors other than chronologic age that predict the toxicity risk with cancer therapy and point the way to interventions that could improve treatment tolerance; and incorporation of a geriatric assessment at sequential time points during and after therapy would provide insight into the impact of cancer therapy on an older adults functional status, comorbidity, psychological state, and cognitive function. The second area of research in geriatric oncology that was highlighted was the need for studies that evaluate the pharmacology of new cancer therapies in older adults. Age-related changes in renal and hepatic function may impact the pharmacokinetics and pharmacodynamics of cancer therapies. In addition, the impact of drug interactions and comorbid medical conditions on the risk of toxicity needs to be studied. Novel dosing regimens to minimize the risk of myelosuppression should be explored, and studies of supportive care measures or other interventions to minimize toxicity are of high research priority. The third area of research that was highlighted was the long-term impact of cancer therapy on cancer survivors. One of the main goals of geriatric medicine is maintenance of function and prolongation of active life expectancy. Quality active life expectancy is dependent on an individuals function, including physical and cognitive performance. This goal is of special concern for older patients with cancer, as some complications of cancer chemotherapy treatment, including cardiomyopathy, neuropathy, or cognitive decline, may have long-term effects on independence and functional status. The interaction between comorbid medical illnesses and the long-term impact of cancer therapy has also been understudied. Although several studies on the potential impact of cancer therapy on cognitive function have emerged,18-21 few studies have addressed the impact of cancer therapy in older adults in general or in those with pre-existing cognitive impairment.22,23 The consensus of the Cancer and Aging Research Group was that research on the long-term impact of cancer therapy on the functional and cognitive status of older cancer survivors is of high priority. A growing number of investigators have developed a clinical and research focus on the issues that face older adults with cancer. In this report, we highlight an approach to help these individuals gain traction as they transition from their training to become independent clinical investigators. The newly formed Cancer and Aging Research Group of junior investigators, mentored by a senior investigator team, has adopted the mission of developing and fostering collaborative research among junior investigators interested in cancer and aging to address the specific issues that face older adults with cancer. Fostering collaboration and mentoring individuals committed to this cause will substantially further the field of geriatric oncology. The Cancer and Aging Research Group has successfully competed for a grant from the Association of Specialty Professors to the American Society of Clinical Oncology Foundation to help support the next meeting of this research group. Its members currently are collaborating on prospective studies designed to address areas of high research priority in geriatric oncology. Additional funding sources are being sought to support the ongoing mentoring and collaborative research efforts of junior investigators in cancer and aging.

Multimorbidity Redefined: Prospective Health Outcomes and the Cumulative Effect of Co-Occurring Conditions

Introduction Multimorbidity is common among middle-aged and older adults; however the prospective effects of multimorbidity on health outcomes (health status, major health decline, and mortality) have not been fully explored. This study addresses this gap in the literature. Methods We used self-reported data from the 2008 and 2010 Health and Retirement Study. Our study population included 13,232 adults aged 50 or older. Our measure of baseline multimorbidity in 2008 was based on the occurrence or co-occurrence of chronic conditions, functional limitations, and/or geriatric syndromes, as follows: MM0, no chronic conditions, functional limitations, or geriatric syndromes; MM1, occurrence (but no co-occurrence) of chronic conditions, functional limitations, or geriatric syndromes; MM2, co-occurrence of any 2 of chronic conditions, functional limitations, or geriatric syndromes; and MM3, co-occurrence of all 3 of chronic conditions, functional limitations, and geriatric syndromes. Outcomes in 2010 included fair or poor health status, major health decline, and mortality. Results All 3 outcomes were significantly associated with multimorbidity. Compared with MM0 (respectively for fair or poor health and major health decline), the adjusted odds ratios (AORs) and 95% confidence intervals were as follows: 2.61 (1.79–3.78) and 2.20 (1.42–3.41) for MM1; 7.49 (5.20–10.77) and 3.70 (2.40–5.71) for MM2; and 22.66 (15.64–32.83) and 4.72 (3.03–7.37) for MM3. Multimorbidity was also associated with mortality: an adult classified as MM3 was nearly 12 times (AOR, 11.87 [5.72–24.62]) as likely as an adult classified as MM0 to die within 2 years. Conclusion Given the strong and significant association between multimorbidity and prospective health status, major health decline, and mortality, multimorbidity may be used — both in clinical practice and in research — to identify older adults with heightened vulnerability for adverse outcomes.

Receipt of appropriate primary breast cancer therapy and adjuvant therapy are not associated with obesity in older women with access to health care.

PURPOSE Many studies have reported body mass index (BMI) increases the risk of breast cancer recurrence and breast cancer-specific mortality. Few studies have reported or examined whether breast cancer treatment differs by BMI. The purpose of this study was to examine the association between BMI at breast cancer diagnosis and receipt of appropriate primary tumor therapy and adjuvant therapy. METHODS We identified 897 women age >or= 65 years diagnosed with stage I or II breast cancer from 1990 to 1999 at five health care organizations. We used medical records to confirm demographics, tumor characteristics, treatment, comorbid conditions, and to calculate BMI at diagnosis (< 25 kg/m(2), n = 328; 25 to < 30 kg/m(2), n = 305; 30 to < 35 kg/m(2), n = 188; >or= 35 kg/m(2), n = 76). We defined primary therapy based on National Guidelines as receiving breast-conserving surgery with radiation therapy and axillary node dissection, simple mastectomy with axillary node dissection, or modified radical mastectomy (73% overall); adjuvant therapy was defined as receipt of hormonal therapy, chemotherapy, or both (60% overall). RESULTS The median BMI was 26.7 kg/m(2) (range, 14.6 to 61.2). The proportion of women receiving primary therapy and adjuvant therapy was lowest for women less than 25 kg/m(2) (69% and 56%, respectively) and greatest for obese I (78% and 64%, respectively). There were no differences in receipt of primary or adjuvant treatment across BMI in univariate or multivariable models (after adjusting for age, stage, comorbidity, diagnosis year, and hormone receptor positivity). CONCLUSION Receipt of appropriate primary therapy and adjuvant therapy is not associated with BMI in older women with access to health care. Additional research in larger samples and more diverse settings is needed.