Gretchen Kimmick

Screening tools for multidimensional health problems warranting a geriatric assessment in older cancer patients: an update on SIOG recommendations†

BACKGROUND Screening tools are proposed to identify those older cancer patients in need of geriatric assessment (GA) and multidisciplinary approach. We aimed to update the International Society of Geriatric Oncology (SIOG) 2005 recommendations on the use of screening tools. MATERIALS AND METHODS SIOG composed a task group to review, interpret and discuss evidence on the use of screening tools in older cancer patients. A systematic review was carried out and discussed by an expert panel, leading to a consensus statement on their use. RESULTS Forty-four studies reporting on the use of 17 different screening tools in older cancer patients were identified. The tools most studied in older cancer patients are G8, Flemish version of the Triage Risk Screening Tool (fTRST) and Vulnerable Elders Survey-13 (VES-13). Across all studies, the highest sensitivity was observed for: G8, fTRST, Oncogeriatric screen, Study of Osteoporotic Fractures, Eastern Cooperative Oncology Group-Performance Status, Senior Adult Oncology Program (SAOP) 2 screening and Gerhematolim. In 11 direct comparisons for detecting problems on a full GA, the G8 was more or equally sensitive than other instruments in all six comparisons, whereas results were mixed for the VES-13 in seven comparisons. In addition, different tools have demonstrated associations with outcome measures, including G8 and VES-13. CONCLUSIONS Screening tools do not replace GA but are recommended in a busy practice in order to identify those patients in need of full GA. If abnormal, screening should be followed by GA and guided multidisciplinary interventions. Several tools are available with different performance for various parameters (including sensitivity for addressing the need for further GA). Further research should focus on the ability of screening tools to build clinical pathways and to predict different outcome parameters.

Adjuvant Hormonal Therapy Use Among Insured, Low-Income Women With Breast Cancer

PURPOSE Use of adjuvant hormonal therapy, which significantly decreases breast cancer mortality, has not been well described among poor women, who are at higher risk of cancer-related death. Here we explore use of adjuvant hormonal therapy in an insured, low-income population. METHODS A North Carolina Cancer Registry-Medicaid linked data set was used. Women with hormone receptor-positive or unknown, nonmetastatic breast cancer, diagnosed between 1998 and 2002, were included. Main outcomes were (1) prescription fill within 1 year of diagnosis, (2) adherence (medication possession ratio), and (3) persistence (absence of a 90-day gap in prescription fills over 12 months). Results The population consisted of 1,491 women (mean age, 67 years). Sixty-four percent filled prescriptions. Predictors of prescription fill included the following: older age (odds ratio [OR], 1.01; P = .017), greater number of prescription medications (OR, 1.06; P < .001), nonmarried status (OR, 1.82; P = .001), higher stage (OR, 1.83; P < .001), positive hormone receptor status (positive v unknown, OR, 1.98; P < .001), not receiving adjuvant chemotherapy (OR, 1.74; P = .001), receipt of adjuvant radiation (OR, 1.55; P = .004), and treatment in a small hospital (OR, 1.49; P = .024). Adherence and persistence rates were 60% and 80%, respectively. Nonmarried status predicted greater adherence (OR, 1.90; P = .006) and persistence (OR, 1.75; P = .031). CONCLUSION Prescription fill, adherence, and persistence to adjuvant hormonal therapy among socioeconomically disadvantaged women are low. Improving use of adjuvant hormonal therapy may lead to lower breast cancer-specific mortality in this population.

Newer Antidepressants and Gabapentin for Hot Flashes: An Individual Patient Pooled Analysis

PURPOSE Nonhormonal treatment options have been investigated as treatments for hot flashes, a major clinical problem in many women. Starting in 2000, a series of 10 individual double-blind placebo-controlled studies has evaluated newer antidepressants and gabapentin for treating hot flashes. This current project was developed to conduct an individual patient pooled analysis of the data from these published clinical trials. PATIENTS AND METHODS Individual patient data were collected from the various study investigators who published their study results between 2000 and 2007. Between-study heterogeneity for study characteristics and patient populations was tested via chi2 tests before a pooled analysis. The primary end point, the change in hot flash activity from baseline to week 4, for each agent was calculated via both weighted and unweighted approaches, using the size of the study as the weight. Basic summary statistics were produced for hot flash score and frequency using the following three statistics: raw change, percent reduction, and whether or not a 50% reduction was achieved. RESULTS This study included seven trials of newer antidepressants and three trials of gabapentin. The optimal doses (defined by individual study results) of the newer antidepressants paroxetine, venlafaxine, fluoxetine, and sertraline decreased hot flash scores by 41%, 33%, 13%, and 3% to 18% compared with the corresponding placebo arms, respectively. The three gabapentin trials decreased hot flashes by 35% to 38% compared with the corresponding placebo arms. CONCLUSION Some newer antidepressants and gabapentin, within 4 weeks of therapy initiation, decrease hot flashes more than placebo.

Randomized, Double-Blind, Placebo-Controlled, Crossover Study of Sertraline (Zoloft) for the Treatment of Hot Flashes in Women with Early Stage Breast Cancer Taking Tamoxifen

Abstract:  We observed the relief of hot flashes in breast cancer survivors taking tamoxifen and treated with sertraline for depression. Our objective was to assess the effect of sertraline on the frequency and severity of hot flashes, mood status, and health‐related quality of life. We used a randomized, double‐blind, placebo‐controlled, crossover study using 6 weeks of sertraline (50 mg each morning) versus placebo. Study participants were 62 breast cancer survivors from an oncology clinic in a tertiary care center on adjuvant tamoxifen reporting bothersome hot flashes. Patients were asked to keep a daily hot flash diary to record hot flash frequency and severity, from which hot flash scores (frequency × severity) were calculated. The Center for Epidemiologic Studies depression scale and Functional Assessment of Cancer Therapy—Breast (FACT‐B) (at baseline, 6 weeks, and 12 weeks) were used to assess mood and quality of life. Sixty‐two women were accrued. Forty‐seven women (median age 53.9 years, range 36.6–77.1 years; 89% postmenopausal; 85.5% Caucasian) completed the first 6 weeks and 39 completed 12 weeks. The baseline daily hot flash frequency and score were 5.8 (standard deviation 4.1) and 11.5 (14.0), respectively. At the end of the first 6 weeks, hot flash frequency decreased by 50% in 36% of those taking sertraline compared to 27% taking placebo. In the crossover analysis, sertraline was significantly more effective than placebo: women crossing from placebo to sertraline had a decrease (−0.9 and −1.7) in hot flash frequency and score, whereas those crossing from sertraline to placebo had an increase (1.5 and 3.4) in hot flash frequency and score (p = 0.03 and 0.03). Forty‐eight percent preferred the sertraline period, 11% preferred the placebo period, and 41% had no preference (p = 0.006). Measures of depression and quality of life were within normal range and did not change significantly within treatment groups. Sertraline decreases hot flashes in breast cancer survivors taking tamoxifen and women prefer sertraline to placebo. Further study of sertraline for the management of hot flashes is warranted. 

Influence of Race, Insurance, Socioeconomic Status, and Hospital Type on Receipt of Guideline-Concordant Adjuvant Systemic Therapy for Locoregional Breast Cancers

PURPOSE For breast cancer, guidelines direct the delivery of adjuvant systemic therapy on the basis of lymph node status, histology, tumor size, grade, and hormonal receptor status. We explored how race/ethnicity, insurance, census tract-level poverty and education, and hospital Commission on Cancer (CoC) status were associated with the receipt of guideline-concordant adjuvant systemic therapy. METHODS Locoregional breast cancers diagnosed in 2004 (n = 6,734) were from the National Program of Cancer Registries-funded seven-state Patterns of Care study of the Centers for Disease Control and Prevention. Predictors of guideline-concordant (receiving/not receiving) adjuvant systemic therapy, according to National Comprehensive Cancer Network Guidelines, were explored by logistic regression. RESULTS Overall, 35% of women received nonguideline chemotherapy, 12% received nonguideline regimens, and 20% received nonguideline hormonal therapy. Significant predictors of nonguideline chemotherapy included Medicaid insurance (odds ratio [OR], 0.66; 95% CI, 0.50 to 0.86), high-poverty areas (OR, 0.77; 95% CI, 0.62 to 0.96), and treatment at non-CoC hospitals (OR, 0.69; 95% CI, 0.56 to 0.85), with adjustment for age, registry, and clinical variables. Predictors of nonguideline regimens among chemotherapy recipients included lack of insurance (OR, 0.47; 95% CI, 0.25 to 0.92), high-poverty areas (OR, 0.71; 95% CI, 0.51 to 0.97), and low-education areas (OR, 0.65; 95% CI, 0.48 to 0.89) after adjustment. Living in high-poverty areas (OR, 0.78; 95% CI, 0.64 to 0.96) and treatment at non-CoC hospitals (OR, 0.68; 95% CI, 0.55 to 0.83) predicted nonguideline hormonal therapy after adjustment. ORs for poverty, education, and insurance were attenuated in the full models. CONCLUSION Sociodemographic and hospital factors are associated with guideline-concordant use of systemic therapy for breast cancer. The identification of modifiable factors that lead to nonguideline treatment may reduce disparities in breast cancer survival.

A Pilot Study of Predictive Markers of Chemotherapy-Related Amenorrhea Among Premenopausal Women with Early Stage Breast Cancer

Background: Premenopausal women treated for early stage breast cancer (ESBC) are at risk for chemotherapy-related amenorrhea (CRA). Prospectively-validated, predictive markers of CRA are needed. Patients and Methods: Premenopausal women with ESBC and planned chemotherapy (≥ 25% risk of amenorrhea) were evaluated. Follicle stimulating hormone (FSH), estradiol, Inhibin A and B, anti-Müllerian hormone (AMH), and quality of life (QOL) were prospectively evaluated pre-, post-, 6 months and 1 year post-chemotherapy and correlated with age and menstrual status. CRA was defined as absence of menses 1 year post-chemotherapy. Results: Forty-four women were evaluated at the time of analysis. Median age at diagnosis and FSH 1 year post-chemotherapy were higher among women with CRA (44 yrs [33–51] vs. 40 yrs [31–43]; p = 0.03; 39.8 vs. 5.0 mLU/mL, p = 0.0058, respectively). Median estradiol 1 year post-chemotherapy was higher among women who resumed menses (108.3 vs. 41.3 pg/mL, p = 0.01). Pre-chemotherapy median Inhibin B and AMH were lower among women with CRA (33.2 vs. 108.8 pg/mL; p = 0.03; 0.16 vs. 1.09 ng/mL, p = 0.02, respectively). The risk of CRA was increased among women with lower pre-chemotherapy Inhibin B (RR = 1.67, p = 0.15) and AMH (RR = 1.83, p = 0.05). Amongst women whose pre-chemotherapy Inhibin B and AMH values were below the median, the incidence of CRA was 87.5%. Conclusions: Results indicate that pre-chemotherapy Inhibin B and AMH are lower among women experiencing CRA and may be predictive of CRA among premenopausal women facing chemotherapy for ESBC.

Vitamin E and breast cancer : A review

Breast cancer is a major health problem in America, accounting for almost one-third of cancer-related deaths in women. The prevention of breast cancer through dietary modification is an active area of clinical and epidemiologic research. It has been proposed that the dietary supplementation of vitamin E, a lipid-soluble antioxidant, may reduce a womans risk of developing breast cancer. In animal models, vitamin E has decreased the incidence of carcinogen-induced mammary tumors. Intake and serum levels of vitamin E and their relation to breast cancer have been evaluated in epidemiologic studies. Results of epidemiologic studies, however, have been conflicting. In this review, we examine the evidence that is available pertaining to the relationship between vitamin E and breast cancer. Although epidemiologic study results have been inconsistent, further study of this nontoxic vitamin is warranted. Particular attention should be paid to the interactions of other antioxidants with vitamin E and to the duration and timing (pre- vs. postmenopausal) of vitamin E use in determining its preventive utility in breast cancer.

Breast cancer and aging. Clinical interactions.

The incidence and mortality rates of breast cancer increase with age. As the geriatric population grows, the number of breast cancer cases will reach epidemic proportions. The number of coexisting medical conditions also increases with advancing age. The presence and severity of comorbid conditions influences an individuals ability to tolerate procedures and treatments and must be considered in making disease-management decisions. Screening mammography can potentially save lives in older women. Women whose life expectancy exceeds 5 years should continue annual screening mammography. Choices for local definitive therapy, systemic adjuvant therapy, and treatment of metastatic disease should be based on patient preference and ability to tolerate the planned procedure. In general, otherwise healthy older women should be offered the same treatment options given to younger, postmenopausal women. Alternative, less aggressive, or nonstandard approaches are warranted in women whose life expectancy is limited or who are unable or unwilling to undergo standard management procedures.

Improving Accrual of Older Persons to Cancer Treatment Trials: A Randomized Trial Comparing an Educational Intervention With Standard Information: CALGB 360001

PURPOSE To design and test a geriatric educational intervention to improve accrual of cancer patients age 65 years and older to cooperative group-sponsored treatment trials. METHODS Main member institutions of the Cancer and Leukemia Group B (CALGB) and its affiliates were randomly assigned to receive standard information (n = 73) or educational intervention (n = 53). Standard information included CALGB Web site access and periodic notification about existing trials. The geriatric educational intervention included standard information plus: (1) an educational seminar; (2) educational materials; (3) a list of available protocols for use on charts; (4) a monthly e-mail and mail reminders for 1 year; and (5) a case discussion seminar. The main outcome was percentage of accrual of older persons to phase II and III treatment protocols after study initiation compared with baseline. RESULTS There were 3,032 patients entered onto trials in the baseline year, and 2,160 and 1,239 during the 2 years postintervention, respectively. Overall percentage of accrual of older patients was 37% at baseline, and 33% and 31% during the first and second years after intervention. There was no improvement in accrual in the intervention versus control arm: 36% v 32% in the first year and 31% v 31% in the second year. CONCLUSION Accrual of older patients was not increased by this intervention. Reasons for lack of effect include low intervention intensity, high baseline accrual rates, and closure of several high-accruing protocols during the study. More intense and multifaceted approaches will be needed to change physician (and patient) behavior and to increase accrual of older persons to clinical trials.

Cancer Chemotherapy in Older Adults A Tolerability Perspective

SummaryThe incidence of cancer increases with age. Since the geriatric population is growing, we will be confronted with an increasing number of patients with cancer who are >65 years of age. The purpose of this review is to address the use of cancer chemotherapy in older persons with respect to its tolerability.We performed a review of the literature using ‘Medline’ and the bibliographies of pertinent publications. Information about cancer treatment in older adults was extracted with particular attention to chemotherapy-related toxicity in patients aged >65 years. Comorbid disease, polypharmacy/drug interactions, psychosocial issues and age-related physiological changes are major issues in caring for older patients with cancer. Since older individuals may have a greater number of comorbid illnesses, treatment should be initiated on the basis of physiological rather than chronological age.Comparative studies show that chemotherapy-related toxicity is similar in older and younger patients, with the exception of haematological toxicity, which may be more severe in older patients, and cardiotoxicity, which is more frequent in the elderly. Other evidence suggests that gastrointestinal and neurotoxicities may also be more severe in older individuals. The dosages of chemotherapeutic agents that are primarily renally excreted may require adjustment in older patients. Haematological reserve is decreased in older individuals, and drugs that cause myelosuppression must be used with care. The use of haemopoietic growth factors in geriatric patients is currently being investigated.