Limin X. Clegg

Annual report to the nation on the status of cancer, 1975–2001, with a special feature regarding survival

The American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updated information regarding cancer occurrence and trends in the U.S. This years report features a special section on cancer survival.

Methods for evaluation of retinal microvascular abnormalities associated with hypertension/sclerosis in the Atherosclerosis Risk in Communities Study

OBJECTIVE To develop protocols to photograph and evaluate retinal vascular abnormalities in the Atherosclerosis Risk in Communities (ARIC) Study; to test reproducibility of the grading system; and to explore the relationship of these microvascular changes with blood pressure. DESIGN Population-based, cross-sectional study. PARTICIPANTS Among 4 examination centers, 11,114 participants (48-73 years of age) at their third triennial examination, after excluding persons with diabetes from this analysis. METHODS One eye of each participant was photographed by technicians with nonmydriatic fundus cameras. Reading center graders evaluated focal arteriolar narrowing, arteriovenous (AV) nicking, and retinopathy by examining slides on a light box and measured diameters of all vessels in a zone surrounding the optic disc on enhanced digitized images. To gauge generalized narrowing, vessel diameters were combined into central arteriolar and venular equivalents with formulas adjusting for branching, and the ratio of equivalents (A/V ratio) was calculated. MAIN OUTCOME MEASURES Retinal vascular abnormalities, mean arteriolar blood pressure (MABP). RESULTS Among 11,114 participants, photographs were obtained of 99%, with quality sufficient to perform retinal evaluations in 81%. In the 9040 subjects with usable photographs, A/V ratio (lower values indicate generalized arteriolar narrowing) ranged from 0.57 to 1.22 (median = 0.84, interquartile range = 0.10), focal arteriolar narrowing was found in 7%, AV nicking in 6%, and retinopathy in 4%. Because of attrition of subjects and limitation of methods, prevalence of abnormality was likely underestimated. Controlling for gender, race, age, and smoking status, these retinal changes were associated with higher blood pressure. For every 10-mmHg increase in MABP, A/V ratio decreased by 0.02 unit (P < 0.0001), focal arteriolar narrowing had an odds ratio (OR) of 2.00 (95% confidence interval [CI] = 1.87-2.14), AV nicking had an OR of 1.25 (95% CI = 1.16-1.34), and retinopathy had an OR of 1.25 (95% CI = 1.15-1.37). For any degree of generalized narrowing, individuals with focal narrowing had MABP approximately 8 mmHg higher than those without (P < 0.0001). Masked replicate assessment of a sample found the following reproducibility: for A/V ratio, correlation coefficient = 0.79 and median absolute difference = 0.03; for focal arteriolar narrowing, kappa = 0.45; for AV nicking, kappa = 0.61; and for retinopathy, kappa = 0.89. CONCLUSION Protocols have been developed for nonmydriatic fundus photography and for evaluation of retinal vascular abnormalities. Several microvascular changes were significantly associated with higher blood pressure; follow-up will show whether these are predictive of later cerebrovascular or cardiovascular disease independently of other known risk factors.

Trends in the incidence of myocardial infarction and in mortality due to coronary heart disease, 1987 to 1994.

BACKGROUND AND METHODS To clarify the determinants of contemporary trends in mortality from coronary heart disease (CHD), we conducted surveillance of hospital admissions for myocardial infarction and of in-hospital and out-of-hospital deaths due to CHD among 35-to-74-year-old residents of four communities of varying size in the United States (a total of 352,481 persons in 1994). Between 1987 and 1994, we estimate that there were 11,869 hospitalizations for myocardial infarction (on the basis of 8572 hospitalizations sampled) and 3407 fatal coronary events (3023 sampled). RESULTS The largest average annual decrease in mortality due to CHD occurred among white men (change in mortality, -4.7 percent; 95 percent confidence interval, -2.2 to -7.1 percent), followed by white women (-4.5 percent; 95 percent confidence interval, -0.7 to -8.2 percent), black women (-4.1 percent; 95 percent confidence interval, -10.3 to +2.5 percent), and black men (-2.5 percent; 95 percent confidence interval, -6.9 to +2.2 percent). Overall, in-hospital mortality from CHD fell by 5.1 percent per year, whereas out-of-hospital mortality declined by 3.6 percent per year. There was no evidence of a decline in the incidence of hospitalization for a first myocardial infarction among either men or women; in fact, such hospital admissions increased by 7.4 percent per year (95 percent confidence interval for the change, +0.5 to +14.8 percent) among black women and 2.9 percent per year (95 percent confidence interval, -3.6 to +9.9 percent) among black men. Rates of recurrent myocardial infarction decreased, and survival after myocardial infarction improved. CONCLUSIONS From 1987 to 1994, we observed a stable or slightly increasing incidence of hospitalization for myocardial infarction. Nevertheless, there were significant annual decreases in mortality from CHD. The decline in mortality in the four communities we studied may be due largely to improvements in the treatment and secondary prevention of myocardial infarction.

Efficient interval estimation for age-adjusted cancer rates

The age-adjusted cancer rates are defined as the weighted average of the age-specific cancer rates, where the weights are positive, known, and normalized so that their sum is 1. Fay and Feuer developed a confidence interval for a single age-adjusted rate based on the gamma approximation. Fay used the gamma approximations to construct an F interval for the ratio of two age-adjusted rates. Modifications of the gamma and F intervals are proposed and a simulation study is carried out to show that these modified gamma and modified F intervals are more efficient than the gamma and F intervals, respectively, in the sense that the proposed intervals have empirical coverage probabilities less than or equal to their counterparts, and that they also retain the nominal level. The normal and beta confidence intervals for a single age-adjusted rate are also provided, but they are shown to be slightly liberal. Finally, for comparing two correlated age-adjusted rates, the confidence intervals for the difference and for the ratio of the two age-adjusted rates are derived incorporating the correlation between the two rates. The proposed gamma and F intervals and the normal intervals for the correlated age-adjusted rates are recommended to be implemented in the Surveillance, Epidemiology and End Results Program of the National Cancer Institute.

Quality-of-life outcomes after primary androgen deprivation therapy: results from the prostate cancer outcomes study

PURPOSE To compare health-related quality-of-life outcomes after primary androgen deprivation (AD) therapy with orchiectomy versus luteinizing hormone-releasing hormone (LHRH) agonists for patients with prostate cancer. PATIENTS AND METHODS Men (n = 431) newly diagnosed with all stages of prostate cancer from six geographic regions who participated in the Prostate Cancer Outcomes Study and who received primary AD therapy but no other treatments within 12 months of initial diagnosis were included in a study of health outcomes. Comparisons were statistically adjusted for patient sociodemographic and clinical characteristics, timing of therapy, and use of combined androgen blockade. RESULTS More than half of the patients receiving primary AD therapy had been initially diagnosed with clinically localized prostate cancer. Among these patients, almost two thirds were at high risk of progression on the basis of prognostic factors. Sexual function outcomes were similar by treatment group both before and after implementation of AD therapy. LHRH patients reported more breast swelling than did orchiectomy patients (24.9% v 9.7%, P <.01). LHRH patients reported more physical discomfort and worry because of cancer or its treatment than did orchiectomy patients. LHRH patients assessed their overall health as fair or poor more frequently than did orchiectomy patients (35.4% v 28.1%, P =.01) and also were less likely to consider themselves free of prostate cancer after treatment. CONCLUSION Most endocrine-related health outcomes are similar after surgical versus medical primary hormonal therapy. Stage at diagnosis had little effect on outcomes. These results provide representative information comparing surgical and medical AD therapy that may be used by physicians and patients to inform treatment decisions.

Estimating average annual per cent change in trend analysis

Trends in incidence or mortality rates over a specified time interval are usually described by the conventional annual per cent change (cAPC), under the assumption of a constant rate of change. When this assumption does not hold over the entire time interval, the trend may be characterized using the annual per cent changes from segmented analysis (sAPCs). This approach assumes that the change in rates is constant over each time partition defined by the transition points, but varies among different time partitions. Different groups (e.g. racial subgroups), however, may have different transition points and thus different time partitions over which they have constant rates of change, making comparison of sAPCs problematic across groups over a common time interval of interest (e.g. the past 10 years). We propose a new measure, the average annual per cent change (AAPC), which uses sAPCs to summarize and compare trends for a specific time period. The advantage of the proposed AAPC is that it takes into account the trend transitions, whereas cAPC does not and can lead to erroneous conclusions. In addition, when the trend is constant over the entire time interval of interest, the AAPC has the advantage of reducing to both cAPC and sAPC. Moreover, because the estimated AAPC is based on the segmented analysis over the entire data series, any selected subinterval within a single time partition will yield the same AAPC estimate—that is it will be equal to the estimated sAPC for that time partition. The cAPC, however, is re-estimated using data only from that selected subinterval; thus, its estimate may be sensitive to the subinterval selected. The AAPC estimation has been incorporated into the segmented regression (free) software Joinpoint, which is used by many registries throughout the world for characterizing trends in cancer rates. Copyright

Physical activity and incidence of coronary heart disease in middle-aged women and men.

Few studies of physical activity and coronary heart disease (CHD) have included women or blacks. We examined this association in a biracial cohort of 45- to 64-yr-old adults. We related the sports, leisure, and work indices developed by J. A. H. Baecke et al. to CHD incident events (N = 97 in women, N = 223 in men) over 4-7 yr in the Atherosclerosis Risk in Communities study. The age-, race-, and field center-adjusted relative risk of CHD was 0.73 in women and 0.82 in men per each standard deviation increment in the sports index (P < 0.05). For the leisure index, these relative risks were 0.78 for both sexes (P < 0.05). The work index was not associated with CHD. These inverse associations held for non-blacks, but there was no association between the sport or leisure indices and CHD among blacks. Vigorous sports participation was strongly inversely associated with CHD, but an independent contribution of nonvigorous activity (e.g., walking) could not be demonstrated conclusively. Adjustment for other risk factors attenuated the relative risks, as one might expect if these risk factors mediated any protective effect of physical activity. Our findings reinforce evidence that regular physical activity should protect women, as well as men, from CHD. Explanations for no association among blacks, if real, are needed.

Trends in Surgery and Chemotherapy for Women Diagnosed With Ovarian Cancer in the United States

PURPOSE We examined patterns of care in a population-based sample of 601 ovarian cancer patients diagnosed in 1991, and a sample of 566 women was selected in 1996 to examine trends in care. PATIENTS AND METHODS Patient cases were sampled from within the Surveillance, Epidemiology, and End Results program. Medical records were reabstracted, and treatment data were verified with the treating physician. RESULTS Across these two time periods, the percentage of women with presumptive stage I, II, and IV disease who received lymph node dissection increased. However, a significant number still were not precisely staged. More than 65% of women with ovarian cancer were given cyclophosphamide in 1991 compared with about 14% in 1996. Paclitaxel increased from 1% to 62% during that time. After adjusting for age, race or ethnicity, registry, income, insurance status, Charlson score, residency training program, and marital status, women with early-stage disease were significantly more often given National Institutes of Health Consensus Development Conference guideline therapy in 1996 than in 1991. However, for women with stage III and IV disease, the use of guideline therapy did not significantly increase. Older women and minorities consistently received less guideline therapy, and the lack of private insurance was an impediment for both Hispanic and non-Hispanic black women. CONCLUSION Despite guidelines presented by several organizations, significant numbers of women with ovarian cancer are not being provided with appropriate care. This is particularly true for older and minority women, especially those without private insurance. Educational strategies must be devised to increase the number of women receiving guideline therapy and decrease disparities across population groups.

Insurance Status and the Use of Guideline Therapy in the Treatment of Selected Cancers

PURPOSE This study estimates the impact of type of insurance coverage on the receipt of guideline therapy in a population-based sample of cancer patients treated in the community. PATIENTS AND METHODS Patients (n = 7,134) from the National Cancer Institutes Patterns of Care studies who were newly diagnosed with 11 different types of cancer were analyzed. The definition of guideline therapy was based on the National Comprehensive Cancer Network treatment recommendations. Insurance status was categorized as a mutually exclusive hierarchical variable (no insurance, any private insurance, any Medicaid, Medicare only, and all other). Multivariate analyses were used to examine the association between insurance and receipt of guideline therapy. RESULTS Adjusting for clinical and nonclinical variables, insurance status was a modest, although statistically significant, determinant of receipt of guideline therapy, with 65% of the privately insured patients receiving recommended therapy compared with 60% of patients with Medicaid. Seventy percent of the uninsured patients received guideline therapy, which was nonsignificantly different compared with private insurance. When stratified by race, insurance was a statistically significant predictor of the receipt of guideline therapy only for non-Hispanic blacks. CONCLUSION Overall, levels of guideline treatment were lower than expected and particularly low for patients with Medicaid or Medicare only. The use of guideline therapy for ovarian and cervical cancer patients and for patients with rectal cancers was unrelated to type of insurance. Of particular concern is the significantly lower use of guideline therapy for non-Hispanic black patients with Medicaid. After adjusting for other factors, only half of these patients received guideline therapy.

Patterns of Care for Adjuvant Therapy in a Random Population-Based Sample of Patients Diagnosed with Colorectal Cancer

OBJECTIVES:Over the past decade, clinical trials have proved the efficacy of treatments for colorectal cancer (CRC). This study tracks dissemination of these treatments for patients diagnosed with stage II and III disease and compares risk of death for those who received guideline therapy to those who did not.METHODS:We conducted a stratified randomly sampled, population-based study of CRC treatment trends in the United States. Multivariate models were used to explore patient characteristics associated with receipt of treatments. We pooled data with a previous study—patients diagnosed in 1987–1991 and 1995. Cox proportional hazards models were used to assess observed cause-specific and all-cause mortality.RESULTS:In 2000, guideline therapy receipt decreased among stage III rectal cancer patients, but increased for stage III colon and stage II rectal cancer patients. As age increased, likelihood of receiving guideline treatment decreased (p < 0.0001). Overall, race/ethnicity was significantly associated with guideline therapy (p = 0.04). Rectal patients were less likely to have received guideline treatment. Consistent with randomized clinical trial findings, all-cause mortality was lower in patients who received guideline therapy, regardless of Charlson comorbidity score.CONCLUSIONS:Mortality was decreased in patients receiving guideline therapy. Although, rates of guideline-concordant therapy are low in community clinical practice, they are apparently increasing. Newer treatment (oxaliplatin, capecitabine) started to disseminate in 2000. Racial disparities, present in 1995, were not detected in 2000. Age disparities remain despite no evidence of greater chemotherapy-induced toxicity in the elderly. More equitable receipt of cancer treatment to all segments of the community will help to reduce mortality.