Grace L. Smith

Future of Cancer Incidence in the United States: Burdens Upon an Aging, Changing Nation

PURPOSEnBy 2030, the United States population will increase to approximately 365 million, including 72 million older adults (age > or = 65 years) and 157 million minority individuals. Although cancer incidence varies by age and race, the impact of demographic changes on cancer incidence has not been fully characterized. We sought to estimate the number of cancer patients diagnosed in the United States through 2030 by age and race.nnnMETHODSnCurrent demographic-specific cancer incidence rates were calculated using the Surveillance Epidemiology and End Results database. Population projections from the Census Bureau were used to project future cancer incidence through 2030.nnnRESULTSnFrom 2010 to 2030, the total projected cancer incidence will increase by approximately 45%, from 1.6 million in 2010 to 2.3 million in 2030. This increase is driven by cancer diagnosed in older adults and minorities. A 67% increase in cancer incidence is anticipated for older adults, compared with an 11% increase for younger adults. A 99% increase is anticipated for minorities, compared with a 31% increase for whites. From 2010 to 2030, the percentage of all cancers diagnosed in older adults will increase from 61% to 70%, and the percentage of all cancers diagnosed in minorities will increase from 21% to 28%.nnnCONCLUSIONnDemographic changes in the United States will result in a marked increase in the number of cancer diagnoses over the next 20 years. Continued efforts are needed to improve cancer care for older adults and minorities.

Randomized trial of an education and support intervention to prevent readmission of patients with heart failure

OBJECTIVESnWe determined the effect of a targeted education and support intervention on the rate of readmission or death and hospital costs in patients with heart failure (HF).nnnBACKGROUNDnDisease management programs for patients with HF including medical components may reduce readmissions by 40% or more, but the value of an intervention focused on education and support is not known.nnnMETHODSnWe conducted a prospective, randomized trial of a formal education and support intervention on one-year readmission or mortality and costs of care for patients hospitalized with HF.nnnRESULTSnAmong the 88 patients (44 intervention and 44 control) in the study, 25 patients (56.8%) in the intervention group and 36 patients (81.8%) in the control group had at least one readmission or died during one-year follow-up (relative risk = 0.69, 95% confidence interval [CI]: 0.52, 0.92; p = 0.01). The intervention was associated with a 39% decrease in the total number of readmissions (intervention group: 49 readmissions; control group: 80 readmissions, p = 0.06). After adjusting for clinical and demographic characteristics, the intervention group had a significantly lower risk of readmission compared with the control group (hazard ratio = 0.56, 95% CI: 0.32, 0.96; p = 0.03) and hospital readmission costs of

Gender, age, and heart failure with preserved left ventricular systolic function

7,515 less per patient.nnnCONCLUSIONSnA formal education and support intervention substantially reduced adverse clinical outcomes and costs for patients with HF.

Outcomes in heart failure patients with preserved ejection fraction: mortality, readmission, and functional decline.

OBJECTIVESnThis study was designed to determine if women are more likely than men to have heart failure (HF) with preserved systolic function after adjustment for potential confounders, including age.nnnBACKGROUNDnAlthough prior evidence suggests an independent association between female gender and preserved left ventricular systolic function (LVSF) in patients with HF, existing studies are limited by referral biases, small sample sizes, or the inability to adjust for a wide range of potential confounding variables.nnnMETHODSnThis is a cross-sectional study using data from retrospective medical chart abstraction of a national sample of Medicare beneficiaries hospitalized with the principal discharge diagnosis of HF in acute-care nongovernmental hospitals in the U.S. between April 1998 and March 1999. Patients were eligible for this analysis if they were age 65 years or older, had documentation of LVSF, and corroboration of the diagnosis of HF. We used multivariable logistic regression to identify the correlates of preserved LVSF, which was defined as qualitatively normal function or quantitatively reported ejection fraction > or =0.50. Stratified regressions by gender were performed to identify significant interactions.nnnRESULTSnOf the 19,710 patients in the analysis, preserved LVSF was present in 6,700 (35%), 79% of whom were women. In contrast, among the 12,956 patients with impaired LVSF, only 49% were women. Patients with preserved LVSF were 1.5 years older than those with impaired LVSF. After adjustment for age and other patient factors, female gender remained strongly associated with preserved LVSF (calculated risk ratio = 1.71; 95% confidence interval 1.63 to 1.78). The association was consistent in all age groups, and was similar in patients with or without coronary artery disease, hypertension, pulmonary disease, renal insufficiency, or atrial fibrillation.nnnCONCLUSIONSnIn elderly patients hospitalized with HF, preserved systolic function is primarily a condition of women, independent of important demographic and clinical characteristics.

The prognostic importance of anemia in patients with heart failure

OBJECTIVESnWe evaluated the six-month clinical trajectory of patients hospitalized for heart failure (HF) with preserved ejection fraction (EF), as the natural history of this condition has not been well established. We compared mortality, hospital readmission, and changes in functional status in patients with preserved versus depressed EF.nnnBACKGROUNDnAlthough the poor prognosis of HF with depressed EF has been extensively documented, there are only limited and conflicting data concerning clinical outcomes for patients with preserved EF.nnnMETHODSnWe prospectively evaluated 413 patients hospitalized for HF to determine whether EF >or=40% was an independent predictor of mortality, readmission, and the combined outcome of functional decline or death.nnnRESULTSnAfter six months, 13% of patients with preserved EF died, compared with 21% of patients with depressed EF (p = 0.02). However, the rates of functional decline were similar among those with preserved and depressed EF (30% vs. 23%, respectively; p = 0.14). After adjusting for demographic and clinical covariates, preserved EF was associated with a lower risk of death (hazard ratio [HR] 0.49, 95% confidence interval [CI] 0.26 to 0.90; p = 0.02), but there was no difference in the risk of readmission (HR 1.01, 95% CI 0.72 to 1.43; p = 0.96) or the odds of functional decline or death (OR 1.01, 95% CI 0.59 to 1.72; p = 0.97).nnnCONCLUSIONSnHeart failure with preserved EF confers a considerable burden on patients, with the risk of readmission, disability, and symptoms subsequent to hospital discharge, comparable to that of HF patients with depressed EF.

Prognostic Significance of Vascular Endothelial Growth Factor Protein Levels in Oral and Oropharyngeal Squamous Cell Carcinoma

Physiologic studies have suggested that anemia could adversely affect the cardiovascular condition of patients with heart failure. Yet, the prognostic importance of this treatable condition is not well established by epidemiologic studies. We sought to determine the prognostic value of hematocrit level in a cohort of elderly patients hospitalized with heart failure. We studied a consecutive sample of 2281 patients aged 65 years or older who had been admitted with a principal discharge diagnosis of heart failure. Multivariate Cox proportional hazards regression was conducted to test whether hematocrit level was an independent predictor of 1-year mortality and of hospital readmission. The mean (+/- SD) age of the patients was 79 +/- 8 years; 58% (n = 1324) were women. Their median hematocrit was 38% (25th to 75th percentile, 33% to 42%). Lower hematocrits were associated with a higher mortality. After adjusting for demographic and clinical factors, each 1% lower hematocrit was associated with a 2% greater 1-year mortality (P = 0.007). Compared with patients with a hematocrit >42%, those with a hematocrit < or =27% had a 40% greater 1-year mortality (hazard ratio [HR] = 1.40; 95% confidence interval [CI]: 1.02 to 1.92; P = 0.04). This increased risk was similar to that conferred by traditional risk factors, including a left ventricular ejection fraction < or =20% (HR = 1.50; 95% CI: 1.20 to 1.86). Lower hematocrits were also associated with a greater risk of hospital readmission. Anemia is associated with an increased risk of death and rehospitalization in older patients with heart failure. Whether anemia is a direct cause of worse outcomes, or a marker for other causal factors, is not known.

Association between treatment with brachytherapy vs whole-breast irradiation and subsequent mastectomy, complications, and survival among older women with invasive breast cancer.

PURPOSEnVascular Endothelial Growth Factor (VEGF) promotes angiogenesis in many different tumor types. VEGF levels may affect tumor growth, metastatic potential, and response to radiotherapy. This study assesses the prognostic value of VEGF protein levels in a cohort of patients with oral and oropharyngeal squamous cell carcinomas. The relationships between clinical outcome and the covariables of tumor-node-metastasis stage, disease stage (I to IV), grade, margin status, race, sex, and age were also determined.nnnPATIENTS AND METHODSnChart review identified 77 patients with oral or oropharyngeal squamous cell carcinoma treated with gross total surgical resection and postoperative radiation between 1981 and 1992. Sufficient follow-up data and tumor tissue were available in 56 patients (73%). VEGF protein levels were determined using immunohistochemistry. The association between VEGF status, covariables, and outcome was assessed in a bivariate and multivariate model using two-sided statistical tests.nnnRESULTSnTwenty-three tumors (41%) were positive for VEGF expression. VEGF-positive tumors were more likely to recur locally (relative risk [RR] = 3.08; 95% confidence interval [CI], 1.03 to 9.24) and distantly (RR = 4.62; 95% CI, 1.41 to 15.10). In bivariate analysis, VEGF positivity was the most significant predictor of poor disease-free survival (RR = 2.66; 95% CI, 1.27 to 5.56) and overall survival (RR = 3.21; 95% CI, 1.63 to 6.32). In multivariate analysis, VEGF positivity was the most significant predictor of poor disease-free survival (RR = 2.75; 95% CI, 1.30 to 5.79) and overall survival (RR = 3.53; 95% CI, 1.75 to 7.13).nnnCONCLUSIONnIn this cohort, VEGF positivity was the most significant predictor of poor prognosis. VEGF status may prove to be an important prognostic factor in head and neck cancer.

Cerebrovascular Disease Risk in Older Head and Neck Cancer Patients After Radiotherapy

CONTEXTnBrachytherapy is a radiation treatment that uses an implanted radioactive source. In recent years, use of breast brachytherapy after lumpectomy for early breast cancer has increased substantially despite a lack of randomized trial data comparing its effectiveness with standard whole-breast irradiation (WBI). Because results of long-term randomized trials will not be reported for years, detailed analysis of clinical outcomes in a nonrandomized setting is warranted.nnnOBJECTIVEnTo compare the likelihood of breast preservation, complications, and survival for brachytherapy vs WBI among a nationwide cohort of older women with breast cancer with fee-for-service Medicare.nnnDESIGNnRetrospective population-based cohort study of 92,735 women aged 67 years or older with incident invasive breast cancer, diagnosed between 2003 and 2007 and followed up through 2008. After lumpectomy 6952 patients were treated with brachytherapy vs 85,783 with WBI.nnnMAIN OUTCOME MEASURESnCumulative incidence and adjusted risk of subsequent mastectomy (an indicator of failure to preserve the breast) and death were compared using the log-rank test and proportional hazards models. Odds of postoperative infectious and noninfectious complications within 1 year were compared using the χ(2) test and logistic models. Cumulative incidences of long-term complications were compared using the log-rank test.nnnRESULTSnFive-year incidence of subsequent mastectomy was higher in women treated with brachytherapy (3.95%; 95% CI, 3.19%-4.88%) vs WBI (2.18%; 95% CI, 2.04%-2.33%; P < .001) and persisted after multivariate adjustment (hazard ratio [HR], 2.19; 95% CI, 1.84-2.61, P < .001). Brachytherapy was associated with more frequent infectious (16.20%; 95% CI, 15.34%-17.08% vs 10.33%; 95% CI, 10.13%-10.53%; P < .001; adjusted odds ratio [OR], 1.76; 1.64-1.88) and noninfectious (16.25%; 95% CI, 15.39%-17.14% vs 9.00%; 95% CI, 8.81%-9.19%; P < .001; adjusted OR, 2.03; 95% CI, 1.89-2.17) postoperative complications; and higher 5-year incidence of breast pain (14.55%, 95% CI, 13.39%-15.80% vs 11.92%; 95% CI, 11.63%-12.21%), fat necrosis (8.26%; 95% CI, 7.27-9.38 vs 4.05%; 95% CI, 3.87%-4.24%), and rib fracture (4.53%; 95% CI, 3.63%-5.64% vs 3.62%; 95% CI, 3.44%-3.82%; P ≤ .01 for all). Five-year overall survival was 87.66% (95% CI, 85.94%-89.18%) in patients treated with brachytherapy vs 87.04% (95% CI, 86.69%-87.39%) in patients treated with WBI (adjusted HR, 0.94; 95% CI, 0.84-1.05; P = .26).nnnCONCLUSIONnIn a cohort of older women with breast cancer, treatment with brachytherapy compared with WBI was associated worse with long-term breast preservation and increased complications but no difference in survival.

Renal Function, Digoxin Therapy, and Heart Failure Outcomes: Evidence from the Digoxin Intervention Group Trial

PURPOSEnCerebrovascular disease is common in head and neck cancer patients, but it is unknown whether radiotherapy increases the cerebrovascular disease risk in this population.nnnPATIENTS AND METHODSnWe identified 6,862 patients (age > 65 years) from the Surveillance, Epidemiology, and End Results (SEER) -Medicare cohort diagnosed with nonmetastatic head and neck cancer between 1992 and 2002. Using proportional hazards regression, we compared risk of cerebrovascular events (stroke, carotid revascularization, or stroke death) after treatment with radiotherapy alone, surgery plus radiotherapy, or surgery alone. To further validate whether treatment groups had equivalent baseline risk of vascular disease, we compared the risks of developing a control diagnosis, cardiac events (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, or cardiac death). Unlike cerebrovascular risk, no difference in cardiac risk was hypothesized.nnnRESULTSnMean age was 76 +/- 7 years. Ten-year incidence of cerebrovascular events was 34% in patients treated with radiotherapy alone compared with 25% in patients treated with surgery plus radiotherapy and 26% in patients treated with surgery alone (P < .001). After adjusting for covariates, patients treated with radiotherapy alone had increased cerebrovascular risk compared with surgery plus radiotherapy (hazard ratio [HR] = 1.42; 95% CI, 1.14 to 1.77) and surgery alone (HR = 1.50; 95% CI, 1.18 to 1.90). However, no difference was found for surgery plus radiotherapy versus surgery alone (P = .60). As expected, patients treated with radiotherapy alone had no increased cardiac risk compared with the other treatment groups (P = .63 and P = .81).nnnCONCLUSIONnDefinitive radiotherapy for head and neck cancer, but not postoperative radiotherapy, was associated with excess cerebrovascular disease risk in older patients.

Adoption of intensity-modulated radiation therapy for breast cancer in the United States

Renal dysfunction is a common complication for patients with heart failure, but its association with clinical outcomes has not been fully characterized. We evaluated the association of glomerular filtration rate (GFR) with heart failure survival and the effect of digoxin on heart failure outcomes across GFR strata. A secondary analysis from the Digitalis Intervention Group trial was conducted of 6800 outpatients with systolic heart failure. Renal function was categorized as estimated GFR (expressed in ml/min per 1.73 m(2)). All-cause mortality (mean, 3 yr) was inversely proportional to GFR (GFR >60, 31% mortality; GFR 30 to 60, 46% mortality; GFR <30, 62% mortality; P < 0.001). Among patients with a GFR <50, lower GFR were associated with greater adjusted mortality risk (GFR <30: hazard ratio [HR], 2.06, 95% confidence interval [CI], 1.69 to 2.51; GFR 30 to 40: HR, 1.42, 95% CI, 1.22 to 1.67; GFR 40 to 50: HR, 1.22, 95% CI, 1.07 to 1.39; GFR 50 to 60: HR, 1.00, referent). In contrast, participants with GFR 60 to 70 had similar risk (HR, 1.00; 95% CI, 0.88 to 1.14) compared with GFR 50 to 60, and those with GFR >70 had a slightly lower mortality hazard (0.89; 95% CI, 0.78 to 1.00). Linear spline analyses confirmed that GFR = 50 was the appropriate risk threshold; above 50, GFR had no association with mortality, whereas below 50, mortality risk increased sharply with declining GFR (spline coefficient, P < 0.0001). Digoxin efficacy did not differ by level of GFR (P = 0.19 for interaction). Renal dysfunction is strongly associated with mortality in stable outpatients with heart failure, notably in patients with estimated GFR <50 ml/min per 1.73 m(2). The effect of digoxin did not differ by level of renal function.