Causes of death among cancer patients.

Background: The purpose of our study was to characterize the causes of death among cancer patients as a function of objectives: (i) calendar year, (ii) patient age, and (iii) time after diagnosis. Patients and methods: US death certificate data in Surveillance, Epidemiology, and End Results Stat 8.2.1 were used to categorize cancer patient death as being due to index-cancer, nonindex-cancer, and noncancer cause from 1973 to 2012. In addition, data were characterized with standardized mortality ratios (SMRs), which provide the relative risk of death compared with all persons. Results: The greatest relative decrease in index-cancer death (generally from > 60% to < 30%) was among those with cancers of the testis, kidney, bladder, endometrium, breast, cervix, prostate, ovary, anus, colorectum, melanoma, and lymphoma. Index-cancer deaths were stable (typically >40%) among patients with cancers of the liver, pancreas, esophagus, and lung, and brain. Noncancer causes of death were highest in patients with cancers of the colorectum, bladder, kidney, endometrium, breast, prostate, testis; >40% of deaths from heart disease. The highest SMRs were from nonbacterial infections, particularly among <50-year olds (e.g. SMR >1,000 for lymphomas, P < 0.001). The highest SMRs were typically within the first year after cancer diagnosis (SMRs 10-10,000, P < 0.001). Prostate cancer patients had increasing SMRs from Alzheimer's disease, as did testicular patients from suicide. Conclusion: The risk of death from index- and nonindex-cancers varies widely among primary sites. Risk of noncancer deaths now surpasses that of cancer deaths, particularly for young patients in the year after diagnosis.

Abcc10 status affects mammary tumour growth, metastasis, and docetaxel treatment response.

BACKGROUND: Resistance to chemotherapeutic agents is a major obstacle to cancer treatment. A group of ABC efflux pumps, the Multidrug Resistance Proteins, is a source of resistance. Herein, we investigated the role of ABCC10 in mammary tumours, given the important role we have defined for ABCC10 in transporting taxanes, and the recognition that some ABCC proteins have roles in tumour growth. METHODS: ABCC10 expression was correlated to human breast cancer subtype using breast tissue microarrays. Real-time quantitative PCR and western blot analysis were used to examine ABCC10 expression in human breast cancer lines. Abcc10(-/-) mice were crossed to MMTV-PyVmT mice to produce Abcc10(-/-) vs Abcc10(+/+) mammary tumours and derivative cell lines. We used allograft and cellular assays to perform baseline and drug sensitization analysis of tumours and cell lines. RESULTS: Clinical sample analyses indicated that ABCC10 was more highly expressed in Her2+ and ER+ than in Her2-, ER-, and triple-negative breast cancer. Unexpectedly, PyVmT; Abcc10(-/-) tumours grew more rapidly than PyVmT; Abcc10(+/+) tumours and were associated with significantly reduced apoptosis and metastasis. PyVmT; Abcc10(-/-) lines were less migratory than PyVmT; Abcc10(+/+) lines. Finally, we showed increased survival of docetaxel-treated MMTV-PyVmT; Abcc10(-/-) mice compared with wild-type mice. CONCLUSIONS: These data identify roles for Abcc10 in breast cancer pathogenesis and in vivo docetaxel resistance.

A requirement for Nedd9 in luminal progenitor cells prior to mammary tumorigenesis in MMTV-HER2/ErbB2 mice.

Overexpression of the NEDD9/HEF1/Cas-L scaffolding protein is frequent, and drives invasion and metastasis in breast, head and neck, colorectal, melanoma, lung and other types of cancer. We have examined the consequences of genetic ablation of Nedd9 in the MMTV-HER2/ERBB2/neu mouse mammary tumor model. Unexpectedly, we found that only a limited effect on metastasis in MMTV-neu;Nedd9(-/-) mice compared with MMTV-neu;Nedd9(+/+) mice, but instead a dramatic reduction in tumor incidence (18 versus 80%), and a significantly increased latency until tumor appearance. Orthotopic reinjection and tail-vein injection of cells arising from tumors, coupled with in vivo analysis, indicated tumors arising in MMTV-neu;Nedd9(-/-) mice had undergone mutational selection that overcame the initial requirement for Nedd9. To better understand the defects in early tumor growth, we compared mammary progenitor cell pools from MMTV-neu;Nedd9(-/-) versus MMTV-neu;Nedd9(+/+) mice. The MMTV-neu;Nedd9(-/-) genotype selectively reduced both the number and colony-forming potential of mammary luminal epithelial progenitor cells, while not affecting basal epithelial progenitors. MMTV-neu;Nedd9(-/-) mammospheres had striking defects in morphology and cell polarity. All of these defects were seen predominantly in the context of the HER2/neu oncogene, and were not associated with randomization of the plane of mitotic division, but rather with depressed expression the cell attachment protein FAK, accompanied by increased sensitivity to small molecule inhibitors of FAK and SRC. Surprisingly, in spite of these significant differences, only minimal changes were observed in the gene expression profile of Nedd9(-/-) mice, indicating critical Nedd9-dependent differences in cell growth properties were mediated via post-transcriptional regulation of cell signaling. Coupled with emerging data indicating a role for NEDD9 in progenitor cell populations during the morphogenesis of other tissues, these results indicate a functional requirement for NEDD9 in the growth of mammary cancer progenitor cells.

The relationships among knowledge, self-efficacy, preparedness, decisional conflict, and decisions to participate in a cancer clinical trial.

BACKGROUND: Cancer clinical trials (CCTs) are important tools in the development of improved cancer therapies; yet, participation is low. Key psychosocial barriers exist that appear to impact a patient's decision to participate. Little is known about the relationship among knowledge, self-efficacy, preparation, decisional conflict, and patient decisions to take part in CCTs. OBJECTIVE: The purpose of this study was to determine if preparation for consideration of a CCT as a treatment option mediates the relationship between knowledge, self-efficacy, and decisional conflict. We also explored whether lower levels of decisional conflict are associated with greater likelihood of CCT enrollment. METHOD: In a pre-post test intervention study, cancer patients (N = 105) were recruited before their initial consultation with a medical oncologist. A brief educational intervention was provided for all patients. Patient self-report survey responses assessed knowledge, self-efficacy, preparation for clinical trial participation, decisional conflict, and clinical trial participation. RESULTS: Preparation was found to mediate the relationship between self-efficacy and decisional conflict (p = 0.003 for a test of the indirect mediational pathway for the decisional conflict total score). Preparation had a more limited role in mediating the effect of knowledge on decisional conflict. Further, preliminary evidence indicated that reduced decisional conflict was associated with increased clinical trial enrollment (p = 0.049). CONCLUSIONS: When patients feel greater CCT self-efficacy and have more knowledge, they feel more prepared to make a CCT decision. Reduced decisional conflict, in turn, is associated with the decision to enroll in a clinical trial. Our results suggest that preparation for decision-making should be a target of future interventions to improve participation in CCTs.

Genetic counselor opinions of, and experiences with telephone communication of BRCA1/2 test results.

BRCA1/2 test disclosure has, historically, been conducted in-person by genetics professionals. Given increasing demand for, and access to, genetic testing, interest in telephone and Internet genetic services, including disclosure of test results, has increased. Semi-structured interviews with genetic counselors were conducted to determine interest in, and experiences with telephone disclosure of BRCA1/2 test results. Descriptive data are summarized with response proportions. One hundred and ninety-four genetic counselors completed self-administered surveys via the web. Although 98% had provided BRCA1/2 results by telephone, 77% had never provided pre-test counseling by telephone. Genetic counselors reported perceived advantages and disadvantages to telephone disclosure. Thirty-two percent of participants described experiences that made them question this practice. Genetic counselors more frequently reported discomfort with telephone disclosure of a positive result or variant of uncertain significance (p < 0.01) than other results. Overall, 73% of participants reported interest in telephone disclosure. Many genetic counselors have provided telephone disclosure, however, most, infrequently. Genetic counselors identify potential advantages and disadvantages to telephone disclosure, and recognize the potential for testing and patient factors to impact patient outcomes. Further research evaluating the impact of testing and patient factors on cognitive, affective, social and behavioral outcomes of alternative models of communicating genetic information is warranted.

Phase II trial of docetaxel-irinotecan combination in advanced esophageal cancer.

BACKGROUND: Preclinical evidence suggests synergy between docetaxel and irinotecan, two drugs active in esophagogastric cancer. We previously demonstrated the safety of docetaxel 35 mg/m2 and irinotecan 50 mg/m2 given on days 1 and 8 of a 21-day schedule. MATERIALS AND METHODS: Patients who had unresectable/metastatic squamous cell carcinoma or adenocarcinoma of the esophagus, measurable disease, Eastern Cooperative Oncology Group performance status of zero to two, and normal bilirubin were eligible. Tumor assessment was carried out every three cycles. RESULTS: We enrolled 29 chemotherapy-naive (CN) and 15 chemotherapy-exposed (CE) eligible patients. Principal toxic effects were diarrhea, neutropenia, and hyperglycemia. There were no toxic deaths. There was one early death, from myocardial infarction. Among 26 CN and assessable patients, there were seven (26.9%) with a partial response (PR) and one (3.8%) with a complete response (CR). There were two PRs and one CR among the patients with CE disease. Median time to progression for CN patients was 4.0 months and for CE patients 3.5 months. Median survival for CN eligible patients was 9.0 months and for CE patients 11.4 months. CONCLUSIONS: Docetaxel-irinotecan combination given on a weekly x 2 of 3 schedule is promising in the treatment of advanced esophageal cancer.

Patterns of prostate cancer treatment by clinical stage and age.

OBJECTIVES: This study analyzed prostate cancer treatment rates by age and clinical stage and contrasted these with rates by most accurate stage. METHODS: We determined surgery and radiation rates by most accurate and clinical stage by using 1996 Surveillance, Epidemiology, and End Results data. RESULTS: Treatment rates by clinical stage vs best stage differ significantly. For example, surgery rates for stages B, C, and D are 37%, 78%, and 13% by most accurate stage but 33%, 6%, and 1% by clinical stage. Treatment patterns by clinical stage vary substantially by age. CONCLUSIONS: Treatment patterns should be described by clinical stage rather than most accurate stage, and they vary by age.

Effect of future costs on cost-effectiveness of medical interventions among young adults: the example of intensive therapy for type 1 diabetes mellitus.

OBJECTIVES: Recent research based on a lifetime utility maximization model has suggested that cost-effectiveness analyses should account for all future costs, including medical costs for related and unrelated illnesses and nonmedical costs. This work has also shown that analyses that omit future costs are biased to favor interventions among the elderly that extend life over interventions that improve quality of life. However, the effect of including future costs on the cost-effectiveness of interventions among the young has not been studied. This article examines the effect of including future costs on the cost-effectiveness of intensive therapy for type 1 diabetes mellitus among young adults. METHODS: By modifying a cost-effectiveness model based on the Diabetes Control and Complications Trial to include future costs, the effect of including future costs on the cost-effectiveness of intensive therapy for type 1 diabetes mellitus among young adults was examined. Future costs added to the model included future costs for medical expenditures for illnesses unrelated to diabetes and future nonmedical expenditures net of earnings. RESULTS: Intensive therapy among young adults led to approximately equal increases in the expected number of years lived before age 65, when people generally produce more than they consume, and after age 65, when the opposite tends to hold. Because the discounted value of savings due to lower mortality before age 65 exceeded the discounted value of later increases in costs due to lower mortality after age 65, accounting for future costs decreased the cost-effectiveness ratio from $22,576 to $9,626 per quality-adjusted life-year. CONCLUSIONS: The inclusion of future costs can significantly improve the cost-effectiveness of interventions that decrease mortality among young adults. The common practice of excluding future costs may bias cost-effectiveness analyses against such interventions.

How patients with diabetes perceive their risk for major complications.

CONTEXT: To educate patients with diabetes about their illness and to motivate these patients to pursue intensive treatment, physicians often inform them about their risk for serious complications. However, little is known about patient perceptions of these risks. OBJECTIVE: To compare patient perceptions of risk for major complications of diabetes with actual risk for these complications. DESIGN: Structured interviews were done to obtain the patient's estimate of their risk for complications. To generate estimates of actual risk for each patient, we used a simulation model based on the Diabetes Control and Complications Trial (DCCT). SETTING: Four university-affiliated diabetes clinics in the midwestern United States. PATIENTS: 139 patients with type 1 diabetes mellitus. MAIN OUTCOME MEASURES: Probability of blindness, end-stage renal disease (ESRD), and lower-leg amputation over 20 years. RESULTS: Participants were young (mean age, 30 years) and reported having had diabetes for an average of 15 years. Seventy-nine percent reported their current diabetic therapy to be "intensive." Ninety-eight percent had completed high school, and 51% were college graduates. The patients' estimates of their risks far exceeded the DCCT estimates for all three complications. The mean patient estimate of the risk for blindness was 31.6% (DCCT estimate, 17.0%), of the risk for ESRD was 33.7% (DCCT estimate, 8.7%), and of the risk for amputation was 25.1% (DCCT estimate, 1.9%). Similarly, patients overestimated the benefit of intensive therapy. They estimated, on average, that intensive therapy would result in a 17.0% absolute risk reduction for blindness (DCCT estimate, 12.2%), an 18.1% risk reduction for ESRD (DCCT estimate, 7.0%), and a 14.2% risk reduction for amputation (DCCT estimate, 1.2%). CONCLUSION: Patients with diabetes overestimated their risk for major complications and the benefits of intensive treatment.

State variation in nursing home mortality outcomes according to do-not-resuscitate status.

BACKGROUND: This study compares mortality outcomes of Medicaid-reimbursed nursing home residents with and without do-not-resuscitate (DNR) orders in two diverse states. METHODS: We used 1994 Minimum Data Set Plus (MDS+) information on 3215 nursing home residents from two states. We used Kaplan-Meier analyses to examine unadjusted mortality among those with and without DNR orders across states. We used a proportional hazard regression with main and interaction variables to model the likelihood of survival in the nursing home. RESULTS: Approximately 27% of nursing home residents with DNR orders in State A die within the year, and approximately 40% of nursing home residents with DNR orders in State B die within the year. Regression results indicate that neither having a DNR order nor state of residence were independently associated with mortality. However, residing in State B and having a DNR order was associated with an increased risk of mortality compared with all others in the sample (risk ratio = 1.73; 95% confidence interval = 1.09, 2.75). CONCLUSION: This study demonstrates that DNR orders are associated with varying mortality across states. Future research is needed to identify the reasons why state level differences exist.

Effectiveness of feeding tubes in nursing home residents with swallowing disorders.

BACKGROUND: Among nursing home residents who stop eating, a common decision for residents, caregivers, and families is the decision to begin tube feeding. This study examines the effectiveness of feeding tubes at reducing mortality among nursing home residents with swallowing disorders and feeding disabilities. METHODS: Data from a version of the Minimum Data Set+ (MDS +) encompassing three different states from calendar years 1993 and 1994 were analyzed. Residents were included in the study if they were not totally dependent on staff for eating upon their first assessment but became totally dependent on staff for eating and had a swallowing disorder at some point during their nursing home stay. We used a proportional hazard regression to examine the relationship of feeding tubes with mortality after total eating dependence occurred. RESULTS: Unadjusted Kaplan-Meier curves found that those with feeding tubes were less likely to die than comparable residents without feeding tubes (p < .001). Estimated survival at 1 year was 39% for those without feeding tubes and 50% for those with feeding tubes. The multivariate results indicated that feeding tubes were associated with a reduced risk of death (risk ratio, 0.71; 95% confidence interval, 0.59, 0.86). CONCLUSIONS: This study provides evidence that tube feeding can be life-prolonging, even if the gain in life is not substantial. Such information can be useful to nursing home staff, residents, and families when trying to decide whether to place a feeding tube in a resident with swallowing disorders and eating disabilities.

Nursing home resident use of care directives.

BACKGROUND: The Patient Self-Determination Act of 1991 requires that nursing homes reimbursed by Medicare or Medicaid inform all residents upon admission of their rights to enact care directives in the event of terminal illness. This study investigated the relationship between care directive use and resident functional status. METHODS: We analyzed a version of the Minimum Data Set (MDS+) from a single state. We selected residents who were admitted to a nursing home in the first half of 1993 and followed them in the nursing home through the end of 1994. We created logistic models to examine independent correlates associated with having an advance directive or a do-not-resuscitate (DNR) order on admission. We then created similar logistic models to examine independent correlates associated with writing an advance directive or DNR order subsequent to admission. RESULTS: Of the 2,780 residents, 11% (292) had advance directives and 17% (466) had DNR orders upon admission. Of those without care directives upon admission, 6% (143) subsequently had an advance directive and 15% (339) subsequently had a DNR order. Cross-sectionally, older individuals and whites were more likely to have a care directive. Having poor cognitive and physical function was associated with having a DNR order upon admission. Longitudinally, longer stayers and whites were more likely to have an advance directive. Residents who lost physical function were more likely to have an advance directive and those who lost cognitive function were more likely to have a DNR order. CONCLUSIONS: Care directive use is influenced by a number of sociodemographic and functional characteristics.

Prior living arrangements and nursing home resident admission ADL characteristics: a study of two states.

OBJECTIVES: This study examines the relationship between prior living arrangements and average activities of daily living (ADL) function upon nursing home admission across two states. METHODS: Minimum Data Set Plus records from 1993 and 1994 on 4,837 Medicaid reimbursed nursing home residents aged 65 years and older from two states were used. Medicaid reimbursed residents were chosen because Medicaid reimbursement policies differ at the state level, and such differences might affect admission characteristics across states. Ordinary least squares models were used to examine the correlates of the number of ADL limitations (range 0-7) upon nursing home admission. RESULTS: Residents in state A had a mean of 5.36 ADL limitations, whereas residents in state B had a mean of 4.83 limitations. Those who lived alone entered the nursing home with 0.61 fewer ADL limitations (p < .001) than those who lived with others. Living alone in state A reduced this association through an increase of 0.31 ADL limitations (p = .012). DISCUSSION: Older Medicaid recipients who live alone enter the nursing home with better physical function than those who live with others. The difference in function between those who live alone and those who live with others varies across the two states.

Parental availability for the care of sick children.

OBJECTIVE: Parents have always played a critical role in the care of sick children. Although parents' roles remain crucial to children's health, parental availability has declined during the past half century. The percentage of women with preschool children who work has risen almost fivefold in 45 years from 12% in 1947 to 58% in 1992. The percentage of women in the paid work force with school-aged children has almost tripled in the same period, from 27.3% to 75.9%. Research has examined the effects of a variety of parental work conditions on children. However, past research has not examined how working conditions affect the ability of parents to care for their sick children. In this article, we examine how often the children of working parents get sick and whether parents receive enough paid leave to care for their sick children. METHODOLOGY: This analysis makes use of two national surveys, which provide complementary information regarding the care of sick children. The National Longitudinal Survey of Youth is a longitudinal survey of a nationally representative probability sample of 12,686 men and women; the National Medical Expenditure Survey is a panel survey of 34,459 people. First, we estimated the family illness burden. Second, we looked in detail at the number of days of sick leave mothers had. Third, we examined whether mothers who had sick leave had it consistently during a 5-year period. Finally, we conducted a logistic regression to determine what factors were significant predictors of both lacking sick leave. RESULTS: More than one in three families faced a family illness burden of 2 weeks or more each year. Yet, 28% of mothers had sick leave none of the time they were employed between 1985 and 1990. Employed mothers of children with chronic conditions had less sick leave than other employed mothers. Thirty-six percent of mothers whose children had chronic conditions had sick leave none of the time they were employed. Although 20% of working parents who did not live in poverty lacked sick leave, 38% of parents who did live in poverty lacked sick leave. The problem is also more marked for nonwhite parents. Although 23% of working white parents lacked paid sick leave, 31% of nonwhite parents lacked sick leave. One in six families that lacked sick leave had to cover for more than 4 weeks of family illness during the year. CONCLUSION: In 1993, the US Congress passed the Family and Medical Leave Act (FMLA). However, by limiting the medical leave to the care of major illnesses, primarily those requiring hospitalization, the FMLA does not address the majority of children's sick care needs. For the common childhood illnesses that are not covered by the FMLA, employed parents often must rely on their sick leave if they are to care for their sick children themselves. Yet, we found that many employed parents lack sick leave. This is particularly true of parents of children with chronic conditions and poor and minority families.