Purpose/Objective(s)Delays in initiating guideline-adherent postoperative radiation therapy (PORT) affect 50% of patients with head and neck squamous cell carcinoma (HNSCC), disproportionately burden racial minorities, are associated with worse survival, and contribute to racial disparities in mortality. This study tests the hypothesis that NDURE (Navigation for Disparities and Untimely Radiation thErapy), a patient navigation-based intervention, will decrease delays in starting guideline-adherent PORT relative to Usual Care (UC).Materials/MethodsThis randomized clinical trial (RCT) included adults with locally-advanced HNSCC (i.e., oral cavity, oropharynx, hypopharynx, larynx or paranasal sinuses) planning to undergo curative-intent surgery and PORT. Preoperatively, patients were randomized to NDURE, a navigation-based intervention that addresses barriers to timely PORT at the patient-, healthcare team-, and organizational-levels, or UC. The primary endpoint was delay in initiating guideline-adherent PORT, defined as starting PORT > 6 weeks after surgery. The secondary endpoint was time-to-PORT (TTP). The difference in PORT delay between arms was evaluated using a binary regression generalized linear model with randomization stratification factors (race, expected PORT facility) as covariates. The difference in TTP between arms was evaluated by estimating hazard ratios (HRs) from Cox proportional hazards models, adjusting for stratification factors. Interactions between race and treatment arm were subsequently added to the binary regression and Cox models to compare racial disparities between arms. To detect a 20% reduction in the primary endpoint of PORT delay (45% vs 25%) assuming a two-sided α = 0.1 and power of 83%, we planned to accrue n=75 patients/arm evaluable for the primary endpoint, up to a total of n=180.ResultsAmong 177 eligible patients randomized to NDURE (n=88) or UC (n=89), 146 patients underwent surgery and had a pathologic indication for PORT. NDURE decreased delays in initiating guideline-adherent PORT relative to UC (model-based PORT delay, 26% vs 61%; risk difference = -35%; 90% CI -48% to -23%; p < 0.001). Median TTP was 39 and 47 days in NDURE and UC, respectively. NDURE improved TTP relative to UC (HR = 1.92; 90% CI 1.43 to 2.58; p < 0.001). The difference in delays in initiating guideline-adherent PORT between Black and White patients was 12% in NDURE vs 24% in UC (p = 0.51). The difference in median TTP between Black and White patients was 1 day in NDURE vs 10 days in UC (NDURE Black/White HR = 0.89; 90% CI 0.48 - 1.53; UC Black/White HR = 0.65; 90% CI = 0.41 - 1.02; p = 0.53).ConclusionIn this RCT of patients with HNSCC undergoing surgery and PORT, NDURE decreased delays in starting guideline-adherent PORT and improved TTP. These data support conducting a large efficacy trial to evaluate patient navigation-based approaches to improving the timeliness and equity of PORT for patients with HNSCC and their effect on oncologic outcomes.

Keratinocyte carcinoma (KC) (also referred to as nonmelanoma skin cancer) is by far the most common form of human cancer. A personal history of KC is well established to be associated with increased risk of recurrent KC and malignant melanoma, a less common yet more fatal form of skin cancer. More surprising is that a substantial body of epidemiologic evidence now indicates that a personal history of KC is significantly associated with an overall elevated risk of noncutaneous malignancies. This association is not limited to one or a few types of cancer but applies across many different types of malignancy. This association has been consistently observed in prospective studies across genders for both major histologic types of KC, basal cell carcinoma and squamous cell carcinoma. The risk of other cancers has been even stronger in those with younger compared with older age of onset of KC.A robust body of evidence lends support to the notion that KC may be a marker of a high cancer-risk phenotype. The underlying mechanisms for this association remain to be elucidated, but the cross-cutting nature of this association across numerous malignancies suggests that research to uncover these mechanisms is a promising line of inquiry that could potentially yield valuable insight into human carcinogenesis.

BackgroundA personal history of keratinocyte carcinoma (KC) is associated with increased risk for other malignancies. To assess the role of inherited cancer predisposition we investigated if family history (FH) of skin cancer plus noncutaneous malignancy is associated with the risk of KC plus another type of cancer.MethodsThis clinic-based case-control study of non-Hispanic Caucasians had three age- and gender-matched groups: KC plus another cancer (n=49), KC only (n=50), and cancer-free controls (n=50). Patients were interviewed to assess FH in first-degree relatives of "skin cancer" and "cancer other than skin cancer." Controls were the referent category for the risk of 1) KC only and 2) KC plus another cancer.ResultsWhen FH was categorized into a four-level variable and evaluated across the 3 study groups, compared to the control group a FH of skin plus noncutaneous malignancy was strongly associated with risk of KC only (OR 9.9; 95% CI 1.7-59.7) and KC plus another cancer (OR 9.8; 95% CI 1.7-57.0). The ORs for FH of skin cancer only were weaker and non-significant for both KC only (OR 4.3) and KC plus another cancer (OR 6.8). FH of noncutaneous malignancy only was null across groups.ConclusionsThe overall pattern of associations, especially the similar associations in patients with KC only and with KC plus another cancer, reinforce the known association between a family and personal history of KC but do not support a link between FH of skin plus noncutaneous malignancy and the KC cancer-prone phenotype.

Background Associations between circulating concentrations of oestrogens, progesterone, and androgens with breast cancer and related risk factors in premenopausal women are not well understood. We aimed to characterise these associations with a pooled analysis of data from seven studies.Methods Individual participant data for prediagnostic sex hormone and sex hormone-binding globulin (SHBG) concentrations were contributed from seven prospective studies. We restricted analyses to women who were premenopausal and younger than 50 years at blood collection, and to women with breast cancer diagnosed before age 50 years. We estimated odds ratios (ORs) with 95% CIs for breast cancer associated with hormone concentrations by conditional logistic regression in cases and controls matched for age, date of blood collection, and day of cycle, with stratification by study and further adjustment for cycle phase. We examined associations of hormones with risk factors for breast cancer in control women by comparing geometric mean hormone concentrations in categories of these risk factors, adjusted for study, age, phase of menstrual cycle, and body-mass index (BMI). All statistical tests were two-sided.Findings We included data for up to 767 women with breast cancer and 1699 controls in the risk analyses. Breast cancer risk was associated with a doubling in concentrations of oestradiol (OR 1.19, 95% CI 1.06-1.35), calculated free oestradiol (1.17, 1.03-1.33), oestrone (1.27, 1.05-1.54), androstenedione (1.30, 1.10-1.55), dehydroepiandrosterone sulphate (1.17, 1.04-1.32), testosterone (1.18, 1.03-1.35), and calculated free testosterone (1.08, 0.97-1.21). Breast cancer risk was not associated with luteal phase progesterone (doubling in concentration OR 1.00, 95% CI 0.92-1.09), and adjustment for other factors had little effect on any of these ORs. Cross-sectional analyses in control women showed several associations of sex hormones with breast cancer risk factors.Interpretation Circulating oestrogens and androgens are positively associated with the risk for breast cancer in premenopausal women.

Associations between circulating concentrations of oestrogens, progesterone, and androgens with breast cancer and related risk factors in premenopausal women are not well understood. We aimed to characterise these associations with a pooled analysis of data from seven studies.

Beneficial relationships exist between food preparation skills and improved dietary quality, and between times spent preparing food and mortality. Food shopping, meal planning, preparation and cooking skills are valuable in supporting good health. Thus experts are proposing nutritional counseling be expanded to include these beneficial behavioral skills. Educational programs delivered by chefs have recently emerged as a way to improve engagement with nutritional guidelines. It is reasonable to assume that a chef with behavior change knowledge and skills, such as coaching, may be more effective in facilitating behavior change. We encourage chefs who wish to be involved in promoting health-related behavior change to consider continuing education in coaching knowledge and skills. We also recommend culinary schools to consider offering these courses, to aspiring chefs. Such programming will not only benefit future clients but also offers a career- enriching professional opportunity to chefs.Credentialed chefs can make a positive health impact and should be included as professionals who are eligible for the impending national certification of health and wellness coaches.

In the United States, lung cancer remains the leading cause of cancer death in both men and women even though an extensive list of risk factors has been well-characterized. Far and away the most important cause of lung cancer is exposure to tobacco smoke through active or passive smoking. The reductions in smoking prevalence in men that occurred in the late 1960s through the 1980s will continue to drive the lung cancer mortality rates downward in men during the first portion of this century. This favorable trend will not persist unless further reductions in smoking prevalence are achieved.

In the USA, lung cancer remains the leading cause of cancer death in both males and females, even though an extensive list of modifiable risk factors has long been identified. The predominant cause of lung cancer is exposure to tobacco smoke, with active smoking causing most cases but passive smoking also contributing to the lung cancer burden. The reductions in smoking prevalence in males that occurred in the late 1960s until the 1980s will continue to drive lung cancer mortality rates downward in males during the first portion of this century, but rates in females have not yet begun to decrease. Asbestos has been identified as responsible for the great majority of mesothelioma cases. Fortunately, exposures to major occupational respiratory carcinogens have largely been controlled, but the population is still exposed to environmental causes of lung cancer, including radon, the second leading cause of lung cancer death. Mesothelioma incidence has begun to reflect limitations on use of asbestos implemented decades ago and should continue to fall if asbestos use is limited and workers are protected.

An increase in mitochondrial DNA (mtDNA) content and decline in mitochondrial function occurs with aging and in response to DNA-damaging agents, including tobacco smoke. We did a cross-sectional study and quantified changes in mtDNA content in a population of individuals with varied smoking and alcohol exposure. Age, smoking history, ethanol intake, and other demographic data were characterized for 604 individuals participating in a screening study for smoking-related upper aerodigestive malignancy. Total DNA was extracted from exfoliated cells in saliva. DNA from a nuclear gene, beta-actin, and two mitochondrial genes, cytochrome c oxidase I and II (Cox I and Cox II), were quantified by real-time PCR. mtDNA content was correlated with age, exposure history, and other variables using multivariate regression analyses. A significant increase (P<0.001) in mtDNA content was noted in smokers (31% and 29% increase for Cox I and Cox II, respectively) and former smokers (31% and 34%) when compared with never smokers. This association persisted after adjustment for other significant factors including age, alcohol drinking, and income (P<0.001). Increased mtDNA content was positively associated with pack-years of smoking (P=0.02). Despite an average smoking cessation interval of 21 years in former smokers, tobacco cessation interval was not statistically significantly associated with mtDNA content. Smoking is associated with increased mtDNA content in a dose-dependent fashion. Mitochondrial DNA alterations in response to smoking persist for several decades after smoking cessation, consistent with long-term, smoking-related damage.

Purpose and Experimental Design: Alterations in mitochondrial DNA (mtDNA) sequence and content have been described in human tissues and tumors in association with smoking exposure. We did quantitative PCR analysis of cytochrome c oxidase (Cox) I and Cox II genes to measure changes in mtDNA content in pretreatment and posttreatment salivary rinses obtained from 76 patients undergoing surgical resection for primary head and neck squamous cell carcinoma. We also examined the relationship between changes in mtDNA content and postoperative radiation therapy, smoking exposure, alcohol intake, and other clinical characteristics.Results: Overall, mtDNA content in posttreatment saliva was significantly decreased. The mean change for Cox I was -0.21 [95% confidence interval (95% CI), -0.44 to 0.01, P = 0.06] and for Cox II was -0.31 (95% Cl, -0.55 to -0.08, P = 0.01). Patients in the radiation therapy group exhibited a significant decrease compared with the nonradiated group (P = 0.03 for Cox I; P = 0.05 for Cox II). In addition, significant decreases in Cox /I(-0.71; 95% Cl, -1.17 to -0.25, P = 0.005) and Cox II (-0.65; 95% Cl, -1.17 to -0.13, P = 0.02) were found in never-smoking patients but not in former or current smokers.Conclusion: Our data suggest that salivary mtDNA content is decreased in never smokers and in response to radiation therapy after primary surgical resection.

Background: Missing data in cancer surveillance records are common; however, little information exists on the types of cases most likely to have missing data, or how missing data influence research or policy. Two clinical elements Often Missing ill surveillance data are histologic grade and stage of disease. Missing data are either not clinically ascertained or not successfully abstracted.Methods: Prostate cancer cases (N=22,217) reported to the Maryland Cancer Registry during 1992-1997 were geocoded by residence and analyzed. Multi-level logistic regression was used to examine case attributes and area-level demographic, economic, and health services characteristics predictive of either missing stage Or grade. A Scanning statistic was used to explore geographic clustering of high and low rates of missing stage and grade within the state, before and after adjustment for significant variables From multi-level models.Results: Older age, black race, missing grade, and higher county-level median Income increased the likelihood of missing stage, whereas more recent year of diagnosis, higher blockgroup-level median income, and county-level decreased the likelihood. Older age, missing or later stage, higher blockgroup-level median income, and more urologists per case in one's county Of residence increased the likelihood of missing tumor grade, and more recent year of diagnosis, higher county-level median income, and rurality decreased the likelihood. Adjustment reduced statistically significant clusters of missing stage from six to two, and clusters of missing grade from three to zero.Conclusions: Results suggest systematic influences oil missing stage and grade, which could be investigated with case-control follow-back studies.

Background: Nicotine replacement therapy (NRT) has been shown to assist smokers to stop smoking in randomized trials, but little is known about its use in the general Population.Methods: As part of ongoing follow-up of a cohort established in 1989 in Washington County, Maryland, a questionnaire mailed in 1998 included a question about ever use of the two NRT products then available over-the-counter: nicotine gum and nicotine patch. This study reports on ever use of NRT among the 1,954 respondents who were Current smokers in 1989 and subsequently provided data on NRT use and smoking habits in 1998.Results: Overall, 36 % of the smokers in 1989 had ever used NRT in some form by 1998; 10 % used gum only, 16 % used patch only, and 10 % used both gum and patch. Number of cigarettes smoked per day at baseline was the strongest predictor of ever use of NRT (P-trend < 0.001). Compared to nonusers, ever users of NRT were more likely to have more than 12 years of education (p < 0.01) and be 25-54 years old at baseline (p < 0.001). When NRT use was assessed in relation to smoking status in 1998, 30 % of NRT ever users compared to 39 % of nonusers had quit smoking (p < 0.01). Among persistent smokers, the likelihood of reducing the number of cigarettes smoked per day was similar between NRT ever users (40 %) and nonusers (41 %).Conclusions: Ever use of NRT was common among this cohort of smokers, particularly among heavy smokers. Compared to nonusers, ever users of NRT were less likely to have stopped smoking and equally likely to cut down the frequency of smoking. This may reflect a tendency to turn to NRT for help after failing to quit by other means. (C) 2005 by The Haworth Press, Inc. All rights reserved.

In the United States, the 20th century witnessed the emergence of a lung cancer epidemic that peaked and began to decline by the century's end, a decline that continues today. However, lung cancer continues to be an unabating pandemic. In research carried out over the last half of the 20th century, many factors were causally associated with lung cancer and studies were implemented to identify determinants of susceptibility to these factors. Cigarette smoking was identified as the single most predominant cause of the lung cancer epidemic, but other causes were found, including workplace agents (eg, asbestos, arsenic, chromium, nickel, and radon) and other environmental factors (passive smoking, indoor radon, and air pollution). Contemporary epidemiologic research on lung cancer now focuses on a new set of issues, primarily related to susceptibility to the well-identified causal factors, particularly smoking, and on the consequences of changes in tobacco products for risks to smokers. Diet and the possibility of reducing risk through chemoprevention remain a focus of research emphasis through experimental and observational approaches. Questions have also been raised about possible differences in susceptibility to lung cancer by sex and race. Population patterns in smoking prevalence will continue to be the most powerful predictor of the future occurrence of lung cancer. Evaluation of recent US patterns in smoking prevalence indicates that for the next approximately 10 to 15 years, lung cancer rates will decrease, but will then level off starting in approximately 2030. Unless further reductions in the prevalence of cigarette smoking are achieved over the next decade, lung cancer will remain as an all too common, but avoidable, disease.

OBJECTIVE: Evidence links active cigarette smoking to cervical neoplasia, but much less is known about the role of passive smoking. Using a prospective cohort design, we examined personal cigarette smoking and household passive smoke exposure in relation to the risk of cervical neoplasia.METHODS: Cohorts were established based on data collected on the smoking status of all household members during private censuses of Washington County, Maryland in 1963 (n = 24,792) and 1975 (n = 26,381). Using the Washington County Cancer Registry, the occurrence of cervical neoplasia in the two cohorts was ascertained from 1963-1978 and from 1975-1994. Poisson regression models were fitted to estimate the relative risk of developing cervical neoplasia associated with active and passive smoking in both cohorts. The referent category for all comparisons was never smokers not exposed to passive smoking.RESULTS: The adjusted relative risk and 95% confidence limits for passive smoking was 2.1 (1.3, 3.3) in the 1963 cohort and 1.4 (0.8, 2.4) in the 1975 cohort. The adjusted relative risk and 95% confidence limits for current smoking were 2.6 (1.7, 4.1) and 1.7 (1.1, 2.6) in the 1963 and 1975 cohort, respectively.CONCLUSION: The associations were in the direction of increased risk for both passive smoking and current active smoking in both the 1963 and 1975 cohorts, but were stronger in the 1963 cohort. The results of this long-term, prospective cohort study corroborate the association between active cigarette smoking and cervical neoplasia and provide evidence that passive smoking is a risk factor for cervical neoplasia. (Obstet Gynecol 2005;105:174-81. (C) 2005 by The American College of Obstetricians and Gynecologists.).

BACKGROUND:Recent reports indicate that age is not a contraindication to pulmonary resection for octogenarians with nonsmall cell lung cancer (NSCLC), but other data are lacking. The purpose of this study was to determine outcomes in these patients, particularly short- and long-term survival with stage I disease.METHODS:A retrospective cohort of 68 octogenarians with NSCLC who underwent curative resection from 1980 to 2002 was followed-up for outcomes.RESULTS:Median age was 82 years old (range, 80-87 years old) consisting of 44 males (65%), with a mean follow-up of 32 months (range, 1-178 months). Operations included: 47 lobectomies (69%), 11 wedge resections (16%), 5 segmentectomies (8%), 4 bilobectomies (6%), and 1 pneumonectomy (1%). There were 31 adenocarcinomas (46%), 18 squamous carcinomas (26%), 12 bronchioalveolar carcinomas (18%), 4 large cell carcinomas (6%), and 3 miscellaneous malignant neoplasms (4%). Median hospital stay was 7 days (range, 3-53 days). Thirty-day mortality was 8.8% (n = 6) with 83% developing cardiopulmonary complications. Overall actuarial survival at 1, 3, and 5 years was 73%, 51%, and 34%, respectively. Of 41 patients (60%) with stage I disease, 23 were T1 lesions. Five-year survival was significantly different between stages Ia and Ib patients (61% and 10%, respectively, p = 0.001). Patients in more advanced stages had a 5-year survival of 3/27 (11%). Multivariate analysis identified advanced tumor stage, lower ASA physical status, and low FEV(1) as factors associated with poorer long-term survival.CONCLUSIONS:The 5-year survival, particularly in patients with stage Ia tumors with favorable ASA and FEV(1), supports the notion that health status and tumor stage outweigh chronologic age in determining surgical candidates.