Yong Fang Kuo

Increasing use of gonadotropin‐releasing hormone agonists for the treatment of localized prostate carcinoma

The role of androgen deprivation therapy in prostate carcinoma is controversial in earlier stages of disease. The authors examined the time trends and patterns of use for androgen deprivation in the form of gonadotropin‐releasing hormone (GnRH) agonists or orchiectomy, in population‐based tumor registries.

Use and outcomes of adjuvant chemotherapy in older women with breast cancer

PURPOSE This study was undertaken to determine patterns and outcomes of adjuvant chemotherapy use in a population-based cohort of older women with primary breast cancer. PATIENTS AND METHODS Women were identified from the Surveillance, Epidemiology, and End Results-Medicare-linked database who met the following criteria: age > or = 65 years, stage I to III breast cancer, and diagnosis between 1991 and 1999. Adjuvant chemotherapy use was ascertained by Common Procedural Terminology J codes. Logistic regression analysis was performed to determine factors associated with chemotherapy use. Multivariate Cox proportional hazards models were used to calculate the hazard of death for women with and without chemotherapy. RESULTS A total of 41,390 women met study criteria, of whom 4,500 (10.9%) received chemotherapy. The use of adjuvant chemotherapy more than doubled during the 1990s, from 7.4% in 1991 to 16.3% in 1999 (P < .0001), with a significant shift toward anthracycline use. Women who were younger, white, with lower comorbidity scores, more advanced stage disease, and estrogen receptor (ER) -negative disease were significantly more likely to receive chemotherapy. Chemotherapy was not associated with improved survival among women with lymph node-negative (LN) disease or LN-positive, ER-positive disease (hazard ratio [HR], 1.05; 95% CI, 0.85 to 1.31). However, among women with LN-positive, ER-negative breast cancer, chemotherapy was associated with a significant reduction in breast cancer mortality (HR, 0.72; 95% CI, 0.54 to 0.96). A similar significant benefit of chemotherapy was seen in the subset of women age 70 years or older (HR, 0.74; 95% CI, 0.56 to 0.97). CONCLUSION In this observational cohort, chemotherapy was associated with a significant reduction in mortality among older women with ER-negative, LN-positive breast cancer.

Cardiac Morbidity of Adjuvant Radiotherapy for Breast Cancer

PURPOSE Adjuvant breast irradiation has been associated with an increase in cardiac mortality, because left-sided breast radiation can produce cardiac damage. The purpose of this study was to determine whether modern adjuvant radiotherapy is associated with increased risk of cardiac morbidity. PATIENTS AND METHODS Data from the Surveillance, Epidemiology, and End Results-Medicare database were used for women who were diagnosed with nonmetastatic breast cancer from 1986 to 1993, had known disease laterality, underwent breast surgery, and received adjuvant radiotherapy. The Cox proportional-hazards model was used to compare patients with left- versus right-sided breast cancer for the end points of hospitalization with the following discharge diagnoses (International Classification of Diseases, 9th Revision codes): ischemic heart disease (410-414, 36.0, and 36.1), valvular heart disease (394-397, 424, 35), congestive heart failure (428, 402.01, 402.11, 402.91, and 425), and conduction abnormalities (426, 427, 37.7-37.8, and 37.94-37.99). RESULTS Eight thousand three hundred sixty-three patients had left-sided breast cancer, and 7,907 had right-sided breast cancer. Mean follow-up was 9.5 years (range, 0 to 15 years). There were no significant differences in patients with left- versus right-sided cancers for hospitalization for ischemic heart disease (9.9% v 9.7%), valvular heart disease (2.9% v 2.8%), conduction abnormalities (9.7% v 9.6%), or heart failure (9.7% v 9.7%). The adjusted hazard ratio for left- versus right-sided breast cancer was 1.05 (95% CI, 0.94 to 1.16) for ischemic heart disease, 1.07 (95% CI, 0.89 to 1.30) for valvular heart disease, 1.07 (95% CI, 0.96 to 1.19) for conduction abnormalities, and 1.05 (95% CI, 0.95 to 1.17) for heart failure. CONCLUSION With up to 15 years of follow-up there were no significant differences in cardiac morbidity after radiation for left- versus right-sided breast cancer.

Reimbursement Policy and Androgen-Deprivation Therapy for Prostate Cancer

BACKGROUND The Medicare Modernization Act led to moderate reductions in reimbursement for androgen-deprivation therapy (ADT) for prostate cancer, starting in 2004 and followed by substantial changes in 2005. We hypothesized that these reductions would lead to decreases in the use of ADT for indications that were not evidence based. METHODS Using the Surveillance, Epidemiology, and End Results (SEER) Medicare database, we identified 54,925 men who received a diagnosis of incident prostate cancer from 2003 through 2005. We divided these men into groups according to the strength of the indication for ADT use. The use of ADT was deemed to be inappropriate as primary therapy for men with localized cancers of a low-to-moderate grade (for whom a survival benefit of such therapy was improbable), appropriate as adjuvant therapy with radiation therapy for men with locally advanced cancers (for whom a survival benefit was established), and discretionary for men receiving either primary or adjuvant therapy for localized but high-grade tumors. The proportion of men receiving ADT was calculated according to the year of diagnosis for each group. We used modified Poisson regression models to calculate the effect of the year of diagnosis on the use of ADT. RESULTS The rate of inappropriate use of ADT declined substantially during the study period, from 38.7% in 2003 to 30.6% in 2004 to 25.7% in 2005 (odds ratio for ADT use in 2005 vs. 2003, 0.72; 95% confidence interval [CI], 0.65 to 0.79). There was no decrease in the appropriate use of adjuvant ADT (odds ratio, 1.01; 95% CI, 0.86 to 1.19). In cases involving discretionary use, there was a significant decline in use in 2005 but not in 2004. CONCLUSIONS Changes in the Medicare reimbursement policy in 2004 and 2005 were associated with reductions in ADT use, particularly among men for whom the benefits of such therapy were unclear. (Funded by the American Cancer Society.).

Limits of observational data in determining outcomes from cancer therapy

Observational data are used increasingly to assess the effectiveness of therapies. However, selection biases are likely to have an impact on results and threaten the validity of these studies.

Risk of the "Androgen Deprivation Syndrome" in Men Receiving Androgen Deprivation for Prostate Cancer

BACKGROUND Androgen deprivation therapy for prostate cancer has been associated with a spectrum of adverse effects, such as depression, memory difficulties, and fatigue, termed the androgen deprivation syndrome. Primary care physicians providing follow-up care for men with prostate cancer will be faced with managing these effects. We therefore sought to estimate the incidence of these effects and, by using a control group, ascertain whether these effects were related to androgen deprivation itself. METHODS We assessed the risk of physician diagnoses of depression, cognitive impairment, or constitutional symptoms in Medicare data following androgen deprivation using a sample of 50 613 men with incident prostate cancer and 50 476 men without cancer, from 1992 through 1997, in the linked Surveillance, Epidemiology, and End Results-Medicare database. Cox proportional hazards regression was used to adjust for confounding variables. RESULTS Of men surviving at least 5 years after diagnosis, 31.3% of those receiving androgen deprivation developed at least 1 depressive, cognitive, or constitutional diagnosis compared with 23.7% in those who did not (P<.001). After adjustment for variables such as comorbidity, tumor characteristics, and age, the risks associated with androgen deprivation were substantially reduced or abolished: relative risk (RR) for depression diagnosis, 1.08 (95% confidence interval [CI], 1.02-1.15); RR for cognitive impairment, 0.99 (95% CI, 0.94-1.04); and RR for constitutional symptoms, 1.17 (95% CI, 1.13-1.22). CONCLUSION Depressive, cognitive, and constitutional disorders occur more commonly in patients receiving androgen deprivation, but this appears to be primarily because patients receiving androgen deprivation are older and have more comorbid conditions and more advanced cancers.

Cognitive status, muscle strength, and subsequent disability in older Mexican Americans

Objectives: To examine the association between Mini‐Mental State Examination (MMSE) score and subsequent muscle strength (measured using handgrip strength) and to test the hypothesis that muscle strength will mediate any association between impaired cognition and incident activity of daily living (ADL) disability over a 7‐year period in elderly Mexican Americans who were initially not disabled.

Pancreatic cancer in the general population: Improvements in survival over the last decade

Background: It is unknown whether the improved survival seen at high-volume centers has been translated to all patients with pancreatic cancer.Objective: To use the Surveillance, Epidemiology, and End Results (SEER) database to evaluate population-based trends in surgical resection and survival.Methods: All patients diagnosed with pancreatic cancer from 1988–1999 were identified. The survival and proportion of patients undergoing surgical resection were compared for each of three equal time periods.Results: There were 24,016 patients with pancreatic cancer. 19,533 had stage data available. 9% had localized, 29% had regional, and 62% had distant disease. Resection rates increased for patients with localized and regional disease over the three time periods. Survival increased for patients with regional and distant disease. For regional pancreatic cancer patients, 2-year survival increased from 9.5% to 13.5% (p<0.0001) and from 21.5% to 28.9% following surgical resection (p=0.002). For resected local/regional pancreatic cancer, the year of diagnosis was and independent predictor of improved survival (p=0.0001).Conclusions: SEER patients with regional and distant pancreatic cancer have improved survival over the past decade in both unadjusted and adjusted models. The improvement is most striking for patients with regional disease and reflects increased resection rates and improved resection techniques over time.

Decline in the Use of Anthracyclines for Breast Cancer

PURPOSE To determine the patterns of use of anthracycline- and taxane-based chemotherapy for breast cancer treatment. METHODS Claims from a 5% national Medicare sample and from a nationally representative claims database (Marketscan) from 1998 to 2009 were used. Patients with International Classification of Diseases (ICD), ninth revision, codes indicating breast cancer, ICD and Common Procedural Terminology codes indicating breast surgery, and claims for chemotherapy between 3 months before and 12 months after surgery comprised the study cohort. Chemotherapy was classified as anthracycline-based or taxane-based, and the percentages of use were calculated. Piecewise regression models were used to identify the inflection points in the rates of chemotherapy use. The effect of patient characteristics on receiving different types of chemotherapy was estimated by multivariable logistic regression models. RESULTS A total of 4,458 patients were included in the Medicare cohort and 30,422 in the private insurance cohort. After 2005, a sharp increase in the use of taxane-based chemotherapy and a decline in anthracycline-based chemotherapy was seen. By 2008 in the Medicare cohort, 51% of patients received taxane-based and 32% received anthracycline-based chemotherapy. By the end of 2008, the majority of patients younger than 65 years were also receiving taxane-based chemotherapy. Patients younger than 35 years were less likely to be treated with a taxane-based regimen, whereas patients who underwent 21-gene recurrence score testing and those treated with trastuzumab were more likely to receive taxane-based chemotherapy. CONCLUSION The use of anthracycline-based chemotherapy has declined, and the majority of patients with breast cancer are instead receiving taxane-based chemotherapy. The potential impact on patient outcomes is unknown.

Relationship Between Test Methodology and Mean Velocity in Timed Walk Tests: A Review

OBJECTIVE To assess the degree to which test methodology affects outcomes in clinical evaluations of walking speed. DATA SOURCES Medline database and reference lists from relevant articles. STUDY SELECTION We conducted electronic searches by using various combinations of terms related to clinical evaluations of walking speed. Resultant abstracts were then reviewed, and the methods and results section of promising full-text articles were searched for detailed descriptions of walk-test methodologies and results. Ultimately, articles were limited to the most common participant groups, older adults (aged) and individuals with neurologic conditions (neuro). The final sample included 46 studies. DATA EXTRACTION Three aspects of test methodology (pace, starting protocol, distance timed) were extracted for use as independent variables. Group mean age was extracted for use as a covariate. Group mean velocity was extracted for use as the dependent variable. Data were extracted by a single investigator. DATA SYNTHESIS Usual and/or comfortable pace was reported nearly twice as often as fast pace in both groups. Static-start protocols were more frequently used in aged studies, whereas dynamic (ie, rolling) starts were more common in neuro studies. Distances of 6 and 10m were most common in aged and neuro studies, respectively. Multivariate analyses (analysis of covariance) showed that only pace was significantly related to the mean velocity in both groups (aged: pace, P<.01; starting protocol, P=.21; distance, P=.05; neuro: pace, P=.01; starting protocol, P=.63; distance, P=.49). However, methodology-related differences in the distribution (95% confidence intervals) of performance scores across certain clinical standards were noted within all 3 methodology variables. CONCLUSIONS Clinical assessments of walking velocity are not conducted uniformly. Common methodologic factors may influence the clinical interpretation of walk performances. Universal walk-test methodology is warranted to improve intergroup comparisons and the development of useful clinical criteria and consensus norms.