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Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.To assess long-term risk of local tumor regrowth, we report updated organ preservation rate and oncologic outcomes of the OPRA trial (ClinicalTrials.gov identifier: NCT02008656). Patients with stage II/III rectal cancer were randomly assigned to receive induction chemotherapy followed by chemoradiation (INCT-CRT) or chemoradiation followed by consolidation chemotherapy (CRT-CNCT). Patients who achieved a complete or near-complete response after finishing treatment were offered watch-and-wait (WW). Total mesorectal excision (TME) was recommended for those who achieved an incomplete response. The primary end point was disease-free survival (DFS). The secondary end point was TME-free survival. In total, 324 patients were randomly assigned (INCT-CRT, n = 158; CRT-CNCT, n = 166). Median follow-up was 5.1 years. The 5-year DFS rates were 71% (95% CI, 64 to 79) and 69% (95% CI, 62 to 77) for INCT-CRT and CRT-CNCT, respectively (P = .68). TME-free survival was 39% (95% CI, 32 to 48) in the INCT-CRT group and 54% (95% CI, 46 to 62) in the CRT-CNCT group (P = .012). Of 81 patients with regrowth, 94% occurred within 2 years and 99% occurred within 3 years. DFS was similar for patients who underwent TME after restaging (64% [95% CI, 53 to 78]) and patients in WW who underwent TME after regrowth (64% [95% CI, 53 to 78]; P = .94). Updated analysis continues to show long-term organ preservation in half of the patients with rectal cancer treated with total neoadjuvant therapy. In patients who enter WW, most cases of tumor regrowth occur in the first 2 years.

BACKGROUND: Older smokers account for the greatest tobacco-related morbidity and mortality in the USA, while quitting smoking remains the single most effective preventive health intervention for reducing the risk of smoking-related illness. Yet, knowledge about patterns of smoking and smoking cessation in older adults is lacking. OBJECTIVE: Assess trends in prevalence of cigarette smoking between 1998 and 2018 and identify patterns and predictors of smoking cessation in US older adults. DESIGN: Retrospective cohort study PARTICIPANTS: Individuals aged 55+ enrolled in the nationally representative Health and Retirement Study, 1998-2018 MAIN MEASURES: Current smoking was assessed with the question: Do you smoke cigarettes now? Quitting smoking was defined as having at least two consecutive waves (between 2 and 4 years) in which participants who were current smokers in 1998 reported they were not currently smoking in subsequent waves. KEY RESULTS: Age-adjusted smoking prevalence decreased from 15.9% in 1998 (95% confidence interval (CI) 15.2, 16.7) to 11.2% in 2018 (95% CI 10.4, 12.1). Among 2187 current smokers in 1998 (mean age 64, 56% female), 56% of those living to age 90 had a sustained period of smoking cessation. Smoking less than 10 cigarettes/day was strongly associated with an increased likelihood of quitting smoking (subdistribution hazard ratio 2.3; 95% CI 1.9, 2.8), compared to those who smoked more than 20 cigarettes/day. CONCLUSIONS: Smoking prevalence among older persons has declined and substantial numbers of older smokers succeed in quitting smoking for a sustained period. These findings highlight the need for continued aggressive efforts at tobacco cessation among older persons.

BackgroundAdults aged ≥ 60 years are often underrepresented in atopic dermatitis (AD) clinical trials; age-related comorbidities may impact treatment efficacy and safety.ObjectiveThe aim was to report dupilumab efficacy and safety in patients aged ≥ 60 years with moderate-to-severe AD.MethodsData were pooled from four randomized, placebo-controlled dupilumab trials of patients with moderate-to-severe AD (LIBERTY AD SOLO 1 and 2, LIBERTY AD CAFÉ, and LIBERTY AD CHRONOS) and stratified by age (

PSICHE (NCT05022914) is a prospective trial to test a [68Ga]Ga- PSMA-11 PET/CT imaging tailored strategy. All evaluable patients had biochemical relapse after surgery and underwent centralized [68Ga]Ga-PSMA-11 PET/CT imaging. The treatment was performed according pre-defined criteria. Observation and re-staging at further PSA progression were proposed to patients with negative PSMA and previous postoperative RT. Prostate bed SRT was proposed to all patients with a negative staging or positive imaging within prostate bed. Stereotactic body radiotherapy (SBRT) to all sites of disease was used for all patients with pelvic nodal recurrence (nodal disease

PURPOSE: Prospective data on the efficacy of a watch-and-wait strategy to achieve organ preservation in patients with locally advanced rectal cancer treated with total neoadjuvant therapy are limited. METHODS: In this prospective, randomized phase II trial, we assessed the outcomes of 324 patients with stage II or III rectal adenocarcinoma treated with induction chemotherapy followed by chemoradiotherapy (INCT-CRT) or chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT) and either total mesorectal excision (TME) or watch-and-wait on the basis of tumor response. Patients in both groups received 4 months of infusional fluorouracil-leucovorin-oxaliplatin or capecitabine-oxaliplatin and 5,000 to 5,600 cGy of radiation combined with either continuous infusion fluorouracil or capecitabine during radiotherapy. The trial was designed as two stand-alone studies with disease-free survival (DFS) as the primary end point for both groups, with a comparison to a null hypothesis on the basis of historical data. The secondary end point was TME-free survival. RESULTS: Median follow-up was 3 years. Three-year DFS was 76% (95% CI, 69 to 84) for the INCT-CRT group and 76% (95% CI, 69 to 83) for the CRT-CNCT group, in line with the 3-year DFS rate (75%) observed historically. Three-year TME-free survival was 41% (95% CI, 33 to 50) in the INCT-CRT group and 53% (95% CI, 45 to 62) in the CRT-CNCT group. No differences were found between groups in local recurrence-free survival, distant metastasis-free survival, or overall survival. Patients who underwent TME after restaging and patients who underwent TME after regrowth had similar DFS rates. CONCLUSION: Organ preservation is achievable in half of the patients with rectal cancer treated with total neoadjuvant therapy, without an apparent detriment in survival, compared with historical controls treated with chemoradiotherapy, TME, and postoperative chemotherapy.

The incorporation of omics approaches into symptom science research can provide researchers with information about the molecular mechanisms that underlie symptoms. Most of the omics analyses in symptom science have used a single omics approach. Therefore, these analyses are limited by the information contained within a specific omics domain (e.g., genomics and inherited variations, transcriptomics and gene function). A multi-staged data-integrated multi-omics (MS-DIMO) analysis integrates multiple types of omics data in a single study. With this integration, a MS-DIMO analysis can provide a more comprehensive picture of the complex biological mechanisms that underlie symptoms. The results of a MS-DIMO analysis can be used to refine mechanistic hypotheses and/or discover therapeutic targets for specific symptoms. The purposes of this paper are to: (1) describe a MS-DIMO analysis using "Symptom X" as an example; (2) discuss a number of challenges associated with specific omics analyses and how a MS-DIMO analysis can address them; (3) describe the various orders of omics data that can be used in a MS-DIMO analysis; (4) describe omics analysis tools; and (5) review case exemplars of MS-DIMO analyses in symptom science. This paper provides information on how a MS-DIMO analysis can strengthen symptom science research through the prioritization of functional genes and biological processes associated with a specific symptom.

PurposeCyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors (CDK4/6i) are highly effective against estrogen receptor-positive (ER+)/HER2- breast cancer; however, intrinsic and acquired resistance is common. Elucidating the molecular features of sensitivity and resistance to CDK4/6i may lead to identification of predictive biomarkers and novel therapeutic targets, paving the way toward improving patient outcomes.Experimental designParental breast cancer cells and their endocrine-resistant derivatives (EndoR) were used. Derivatives with acquired resistance to palbociclib (PalboR) were generated from parental and estrogen deprivation-resistant MCF7 and T47D cells. Transcriptomic and proteomic analyses were performed in palbociclib-sensitive and PalboR lines. Gene expression data from CDK4/6i neoadjuvant trials and publicly available datasets were interrogated for correlations of gene signatures and patient outcomes.ResultsParental and EndoR breast cancer lines showed varying degrees of sensitivity to palbociclib. Transcriptomic analysis of these cell lines identified an association between high IFN signaling and reduced CDK4/6i sensitivity; thus an "IFN-related palbociclib-resistance Signature" (IRPS) was derived. In two neoadjuvant trials of CDK4/6i plus endocrine therapy, IRPS and other IFN-related signatures were highly enriched in patients with tumors exhibiting intrinsic resistance to CDK4/6i. PalboR derivatives displayed dramatic activation of IFN/STAT1 signaling compared with their short-term treated or untreated counterparts. In primary ER+/HER2- tumors, the IRPS score was significantly higher in lumB than lumA subtype and correlated with increased gene expression of immune checkpoints, endocrine resistance, and poor prognosis.ConclusionsAberrant IFN signaling is associated with intrinsic resistance to CDK4/6i. Experimentally, acquired resistance to palbociclib is associated with activation of the IFN pathway, warranting additional studies to clarify its involvement in resistance to CDK4/6i.

An older, more diverse population and longer lifespans are major contributors to the anticipated tripling of diabetes prevalence by 2050. Diabetes-related distress affects up to 40% of people with diabetes and may be a higher risk for older adults due to greater prevalence of comorbidities. The objective of the current phenomenological study was to describe how diabetes-related distress might be uniquely experienced by older adults (age ≥65) with type 2 diabetes mellitus (T2DM). Interpretive phenomenology guided the research design and analysis. Everyday life experiences of living with T2DM and elevated diabetes distress were investigated with interpretive interviews. The most prevalent lived experiences were strained relationships with health care providers, guilt, fear, loneliness, and forgetfulness. These experiences created challenges in managing diabetes and increased diabetes-related distress. Improving knowledge regarding the lived experience of older adults with diabetes-related distress may allow health care providers to tailor treatment to this population, thus improving outcomes. [Journal of Gerontological Nursing, 46(3), 37-44.].

BackgroundPatients with lung cancer (LC) report lower quality of life (QoL) and higher levels of psychological distress compared with other cancer populations. Lung cancer stigma (LCS) may in part explain these findings.AimWe investigated the prevalence of patient-perceived lung cancer stigma (LCS) and its relationships to symptom burden/severity, depression, and deficits in health-related quality of life (HR-QoL).MethodsIn this descriptive, observational, and cross-sectional study, 201 participants were sent questionnaires. These included the Cataldo Lung Cancer Stigma Scale (CLCSS), the Lung Cancer Symptom Scale, the Centre for Epidemiologic Studies-Depression Scale, and the Quality of Life Inventory.ResultsParticipants were on average 69 years old, 52% women, 95% ever smokers, and 18.5% current smokers. The mean total CLCSS score was 53.1 (SD = 14.1; range = 31-94). LCS was significantly correlated with younger age (P

BackgroundAn older, more diverse population and longer life spans are major contributors to the anticipated tripling of Type 2 diabetes prevalence by 2050. Diabetes-related distress affects up to 40% of people diagnosed with Type 2 diabetes and may be a greater risk for older adults due to greater prevalence of comorbidities.ObjectiveThe objective of this phenomenological study was to describe how diabetes-related distress in older adults (≥65 years) with Type 2 diabetes might be uniquely experienced.MethodsParticipants were recruited using convenience sampling and snowball sampling. Interpretive phenomenology guided the research design and analysis. With interpretive interviews, we investigated the everyday health, symptoms, and life experiences of living with Type 2 diabetes and elevated diabetes distress.ResultsAmong the older adults in this study, the most prevalent symptoms were fatigue, hypoglycemia, diarrhea, pain, loss of balance, and falling. These diabetes-related symptoms led to substantial loss of independence, decreased quality of life, and constrained social lives due to restricted activities.DiscussionDiabetes-related distress presents with some unique symptoms and responses in older adults. Improving knowledge regarding the symptom experience of older adults with diabetes-related distress may allow healthcare providers to tailor treatment and thus improve outcomes for older adults struggling with diabetes.

In the last 20 years, the United States has made stunning progress reducing the rate of adult smoking. However, the smallest reduction is among older adults. Compared to younger smokers, older smokers are more likely to be lower socioeconomic status (SES), have several tobacco related comorbidities, and are less likely to be treated for tobacco addiction yet, in tobacco policy, they are not considered a marginalized group. The tobacco industry's interest in older smokers contrasts with the lack of interest shown by tobacco control. A double whammy is a set of two bad events or situations that have an effect at the same time. The purposes of this article are to use the health disparity paradigm to (a) discuss the "double whammy" of marginalization by tobacco control and valuation by the tobacco industry on the health of older smokers and (b) provide strategies to promote health equity for older smokers.

BackgroundMany health conditions perceived to be contagious, dangerous or incurable, or resulting in clearly visible signs, share a common attribute - an association with stigma and discrimination. While the etiology of stigma may differ between conditions and, sometimes, cultural settings, the manifestations and psychosocial consequences of stigma and discrimination are remarkably similar. However, the vast majority of studies measuring stigma or addressing stigma through interventions employ a disease-specific approach.Main bodyThe current paper opposes this siloed approach and advocates a generic concept of 'health-related stigma' in both stigma measurement and stigma interventions. Employing a conceptual model adapted from Weiss, the current paper demonstrates the commonalities among several major stigmatized conditions by examining how several stigma measurement instruments, such as the Social Distance Scale, Explanatory Model Interview Catalogue, Internalized Stigma of Mental Illness, and Berger stigma scale, and stigma reduction interventions, such as information-based approaches, contact with affected persons, (peer) counselling, and skills building and empowerment, were used successfully across a variety of conditions to measure or address stigma. The results demonstrate that 'health-related stigma' is a viable concept with clearly identifiable characteristics that are similar across a variety of stigmatized health conditions in very diverse cultures.ConclusionA more generic approach to the study of health-related stigma opens up important practical opportunities - cross-cutting measurement and intervention tools are resource saving and easier to use for personnel working with multiple conditions, allow for comparison between conditions, and recognize the intersectionality of many types of stigma. Further research is needed to build additional evidence demonstrating the advantages and effectiveness of cross-condition approaches to stigma measurement and interventions.

ContextPain may be a potentially modifiable risk factor for expensive and burdensome emergency department (ED) visits near the end of life for older adults with dementia.ObjectivesThe objective of this study was to assess the effect of pain and unmet need for pain management on ED visits in the last month of life in older adults with dementia.MethodsThis is a mortality follow-back study of older adults with dementia in the National Health and Aging Trends Study who died between 2012 and 2014, linked to Medicare claims.ResultsTwo hundred eighty-one National Health and Aging Trends Study decedents with dementia met criteria (mean age 86 years, 61% female, 81% white). Fifty-seven percent had at least one ED visit in the last month of life, and 46.5% had an ED visit that resulted in a hospital admission. Almost three out of four (73%) of decedents experienced pain in the last month of life, and 10% had an unmet need for pain management. After adjustment for age, gender, race, educational attainment, income, comorbidities, and impairment in activities of daily living, pain was not associated with increased ED use in the last month of life (adjusted incident rate ratio 0.87, 95% CI 0.64-1.17). However, decedents with unmet need for pain management had an almost 50% higher rate of ED visits in the last month of life than those without unmet needs (adjusted incident rate ratio 1.46, 95% CI 1.07-1.99).ConclusionAmong older adults with dementia, unmet need for pain management was associated with more frequent ED visits in the last month of life.

BackgroundBy 2030, the Sub-Saharan African region is projected to be the epicenter of the tobacco epidemic. While smoking prevalence is currently low among women ( 94%); however, specific knowledge of associated health-risks was limited. More than 96% perceived female tobacco use as socially unacceptable. At the same time, more than 70% were able to name potential benefits of using tobacco for both personal consumption and non-personal use. Respondents reported greater experimentation with khat versus tobacco and 73% reported that their religion significantly influenced their tobacco-related attitudes. Overall, there were higher reports of exposure to anti-tobacco (70%) versus pro-tobacco (49%) messaging, in the last 30 days.ConclusionsThe high level of awareness of health risks associated with tobacco use and SHS exposure and the high exposure to anti-tobacco messaging are community-level strengths that can proactively be built on to prevent the projected disease burden associated with tobacco. Findings have implications for the development of contextualized gender-specific tobacco control interventions, particularly in relation to the promotion of smoke-free homes.

IntroductionOlder Chinese Americans often defer end-of-life care discussions. Researchers sought to explore how to engage older Chinese Americans and their families in end-of-life care discussions and to understand the optimal timing to initiate such discussions.MethodsIndividual, semistructured interviews were conducted with 14 community-dwelling older Chinese Americans, 9 adult children, and 7 clinicians. The data were collected and analyzed using focused ethnographic methodology.ResultsOlder Chinese Americans and their families would discuss end-of-life care when introduced at "optimal times," which included after-triggering events (e.g., death of loved ones, fall accidents), changes in health status, or advanced age.DiscussionAdult children are not expected to initiate end-of-life care discussions with their parents. Thus, culturally congruent health care that could better engage Chinese Americans in such discussions would be optimized by having clinicians proactively assess their patients' readiness and initiate such discussion at optimal times.

BackgroundAdding modified FOLFOX6 (folinic acid, fluorouracil, and oxaliplatin) after chemoradiotherapy and lengthening the chemoradiotherapy-to-surgery interval is associated with an increase in the proportion of rectal cancer patients with a pathological complete response.ObjectiveThe purpose of this study was to analyze disease-free and overall survival.DesignThis was a nonrandomized phase II trial.SettingsThe study was conducted at multiple institutions.PatientsFour sequential study groups with stage II or III rectal cancer were included.InterventionAll of the patients received 50 Gy of radiation with concurrent continuous infusion of fluorouracil for 5 weeks. Patients in each group received 0, 2, 4, or 6 cycles of modified FOLFOX6 after chemoradiation and before total mesorectal excision. Patients were recommended to receive adjuvant chemotherapy after surgery to complete a total of 8 cycles of modified FOLFOX6.Main outcome measuresThe trial was powered to detect differences in pathological complete response, which was reported previously. Disease-free and overall survival are the main outcomes for the current study.ResultsOf 259 patients, 211 had a complete follow-up. Median follow-up was 59 months (range, 9-125 mo). The mean number of total chemotherapy cycles differed among the 4 groups (p = 0.002), because one third of patients in the group assigned to no preoperative FOLFOX did not receive any adjuvant chemotherapy. Disease-free survival was significantly associated with study group, ypTNM stage, and pathological complete response (p = 0.004,

BackgroundHealth-care providers (HCPs) find facilitating end-of-life (EOL) care discussions challenging, especially with patients whose ethnicities differ from their own. Currently, there is little guidance on how to initiate and facilitate such discussions with older Chinese Americans (≥55 years) and their families.ObjectiveTo explore communication strategies for HCPs to initiate EOL care discussions with older Chinese Americans in the San Francisco Bay Area.DesignThis qualitative (focused) ethnographic study included field observations and individual semistructured interviews with 14 community-dwelling older Chinese Americans who lived independently at home, 9 adult children, and 7 HCPs. Responses were analyzed using open coding, memos, and comparison across participants.ResultsThe study participants emphasized the importance of assessing readiness for early EOL care discussions. All recommended using indirect communication approaches to determine older Chinese Americans' readiness. Indirect communication can be culturally targeted and applied at both system-wide (ie, health-care system) and individual (ie, HCP) levels. To institutionalize the practice, health-care facilities should implement EOL care discussion inquiries as part of routine during check-in or intake questionnaires. In individual practice, using depersonalized communication strategies to initiate the discussion was recommended to determine older Chinese Americans' readiness.ConclusionAssessing readiness should be an essential and necessary action for early EOL care discussions. Culturally targeted assessment of older Chinese Americans includes using indirect communication approaches to initiate an EOL care discussion to determine their readiness. In addition to health-care system integration, providers should implement and evaluate proposed EOL discussion initiation prompts with their older Chinese American patients.

Objective Whereas controversy about the e-cigarette's effectiveness and safety as a smoking cessation tool continues, e-cigarette use prevalence continues rising. In this study, we sought to describe experiences of adult e-cigarette users and to examine their motivations, beliefs, and use patterns. Methods This qualitative study included one-on-one semi-structured phone interviews with 20 current California e-cigarette users (mean age = 38 ± 9.44 years). Interviews were transcribed and thematically analyzed using MAXQDA. Results E-cigarettes initially addressed participants' problems related to smoking; they no longer smelled like cigarette smoke and could avoid smoke-free regulations. Participants highlighted the importance of e-cigarette flavors and of "receiving moral credit" for harm reduction by using e-cigarettes to quit smoking cigarettes. Many described eventual dissatisfaction with e-cigarettes, which resulted in relapse to cigarette smoking and/or dual use with cigarettes. The convenience of e-cigarettes coupled with the pattern of constant use left participants increasingly reliant on e-cigarettes. Conclusion Ultimately, failed cessation and dual use exposes smokers to greater levels of nicotine, while still exposing them to cigarette smoke. Public health campaigns should promote awareness of the risks of using e-cigarettes, including failed cessation attempts, dual use, addiction, and other health consequences.

Due to marijuana's analgesic effects and its growing national legal status, it is likely that marijuana's rising prevalence will impact prescription pain reliever (PPR) use. The present study investigates the relationship between marijuana and PPR use among U.S. adult current cigarette smokers. Data were analyzed from the Tobacco and Attitudes Beliefs Survey II, with 348 current cigarette smokers, aged 24-88. Logistic regression was used to examine the likelihood of current (past 30 days) PPR use by marijuana use (never, ever, and current) among cigarette smokers. Among PPR users (N = 76), we also investigated whether marijuana use frequency predicted current PPR use. Compared to never marijuana users, participants were more likely to report past 30-day PPR use if they have ever used marijuana (AOR: 2.58, 95% CI: 1.51-4.43) or have used marijuana in the past 30 days (AOR: 3.38, CI: 1.76-6.49). No significant relationship was found between marijuana use frequency and PPR use. Thus, in this sample of adult cigarette smokers, past and current marijuana users were two to three times more likely to report PPR use than never marijuana users. These findings can help inform policymakers and healthcare providers in their fight against the opioid epidemic.

PurposeFindings regarding changes in the quality of life (QOL) of patients with gastrointestinal cancers (GI) undergoing chemotherapy (CTX) are inconclusive. Purpose was to evaluate for changes in QOL scores of patients with GI cancers over two cycles of CTX.MethodsPatients (n = 397) completed disease-specific [i.e., Quality of Life-Scale-Patient Version (QOL-PV)] and generic [12-item Medical Outcomes Study Short Form Survey (SF-12)] measures of QOL a total of six times over two cycles of CTX. Changes in these QOL scores were evaluated using bootstrapped multilevel regression with full information maximum likelihood estimation. Treatment group (i.e., with or without targeted therapy), age, number of metastatic sites, time from cancer diagnosis, number of prior cancer treatments, GI cancer diagnosis (i.e., colon/rectum/anal vs. other), and CTX regimen were evaluated as covariates in the conditional models for each of the QOL scores.ResultsDuring the second cycle of CTX, QOL-PV scores decreased in the week following CTX administration, and then increased the following week. For both cycles of CTX, the physical component summary and mental component summary scores of the SF-12 decreased in the week following CTX administration and then increased the following week. Increased time from cancer diagnosis and a higher number of prior cancer treatments resulted in worse QOL-PV and SF-12 scores at enrollment.ConclusionsWhile changes in QOL scores over the two CTX cycles were statistically significant, the differences were not clinically meaningful. Future studies need to determine the optimal timing of QOL assessments to assess changes associated with cancer treatments.

BackgroundBreast cancer treatments can change women's hormonal milieu and alter their symptom experience. Little is known about associations between menopausal status and menopausal symptoms in women with breast cancer before surgery.ObjectiveThe purpose of this study was to evaluate for differences in occurrence, severity, and distress of symptoms between premenopausal and postmenopausal women before breast cancer surgery.MethodsA total of 312 women with breast cancer completed the Menopausal Symptoms Scale, a self-report measure that evaluated the occurrence, severity, and distress of 46 common symptoms associated with menopause. Regression analyses were used to evaluate for between-group differences in these symptoms.ResultsOf the 312 patients enrolled, 37.4% (n = 116) were premenopausal, and 62.6% (n = 196) were postmenopausal. In the multivariate analysis that adjusted for 7 covariates, premenopausal patients reported higher occurrence rates for urinary frequency (P = .006) and reported lower occurrence rates for joint pain/stiffness (P = .011), difficulty falling asleep (P = .025), and vaginal dryness (P = .002). A significant interaction was found between age and menopausal status for hot flashes (P = .002), wake during the night (P = .025), and headache (P = .040).ConclusionRegardless of menopausal status, women reported high occurrence rates for several menopausal symptoms. Associations between some symptom occurrence rates and menopausal status depended on the patients' age.Implications for practiceAs part of a preoperative symptom assessment, clinicians need to consider a woman's menopausal status and salient demographic and clinical characteristics. The identification of women with a higher symptom burden will assist with more effective management.

CONTEXT: Approximately 60% to 100% of women with breast cancer experience at least one menopausal-related symptom. Little is known about associations between menopausal status and symptoms in women 12 months after breast cancer surgery. OBJECTIVES: The purpose of this study was to evaluate for differences in occurrence, severity, and distress of symptoms between pre- and postmenopausal women 12 months after breast cancer surgery. METHODS: Women with breast cancer (n = 327) completed the Menopausal Symptoms Scale, which evaluated the occurrence, severity, and distress of 46 common menopausal-related symptoms. Regression analyses were used to evaluate between-group differences in the seven symptoms that occurred in 30% and more of the sample (i.e., hot flashes, night sweats, depression, daytime sweats, joint pain or stiffness, wake during the night, and numbness or tingling). RESULTS: Of the 327 patients with breast cancer, who completed the 12-month assessment, 35.2% were premenopausal and 64.8% were postmenopausal before surgery. In the conditional models, when significant interactions were found, the differences in symptom occurrence rates between pre- and postmenopausal patients depended on their age. CONCLUSION: Regardless of menopausal status, women reported relatively high occurrence rates for several menopausal symptoms. Associations between symptom occurrence rates and menopausal status depended on the patients age. During the development of a survivorship care plan, clinicians need to assess symptom burden within the context of a womans menopausal status and salient demographic and clinical characteristics. This approach will assist with the prescription of more effective interventions.

ContextApproximately 60% to 100% of women with breast cancer experience at least one menopausal-related symptom. Little is known about associations between menopausal status and symptoms in women 12 months after breast cancer surgery.ObjectivesThe purpose of this study was to evaluate for differences in occurrence, severity, and distress of symptoms between pre- and postmenopausal women 12 months after breast cancer surgery.MethodsWomen with breast cancer (n = 327) completed the Menopausal Symptoms Scale, which evaluated the occurrence, severity, and distress of 46 common menopausal-related symptoms. Regression analyses were used to evaluate between-group differences in the seven symptoms that occurred in 30% and more of the sample (i.e., hot flashes, night sweats, depression, daytime sweats, joint pain or stiffness, wake during the night, and numbness or tingling).ResultsOf the 327 patients with breast cancer, who completed the 12-month assessment, 35.2% were premenopausal and 64.8% were postmenopausal before surgery. In the conditional models, when significant interactions were found, the differences in symptom occurrence rates between pre- and postmenopausal patients depended on their age.ConclusionRegardless of menopausal status, women reported relatively high occurrence rates for several menopausal symptoms. Associations between symptom occurrence rates and menopausal status depended on the patient's age. During the development of a survivorship care plan, clinicians need to assess symptom burden within the context of a woman's menopausal status and salient demographic and clinical characteristics. This approach will assist with the prescription of more effective interventions.

ContextStudies on multiple dimensions of the symptom experience of patients with gastrointestinal cancers are extremely limited.ObjectivePurpose was to evaluate for changes over time in the occurrence, severity, and distress of seven common symptoms in these patients.MethodsPatients completed Memorial Symptom Assessment Scale, six times over two cycles of chemotherapy (CTX). Changes over time in occurrence, severity, and distress of pain, lack of energy, nausea, feeling drowsy, difficulty sleeping, and change in the way food tastes were evaluated using multilevel regression analyses. In the conditional models, effects of treatment group (i.e., with or without targeted therapy), age, number of metastatic sites, time from cancer diagnosis, number of prior cancer treatments, cancer diagnosis, and CTX regimen on enrollment levels, as well as the trajectories of symptom occurrence, severity, and distress were evaluated.ResultsAlthough the occurrence rates for pain, lack of energy, feeling drowsy, difficulty sleeping, and change in the way food tastes declined over the two cycles of CTX, nausea and numbness/tingling in hands/feet had more complex patterns of occurrence. Severity and distress ratings for the seven symptoms varied across the two cycles of CTX.ConclusionsDemographic and clinical characteristics associated with differences in enrollment levels as well as changes over time in occurrence, severity, and distress of these seven common symptoms were highly variable. These findings can be used to identify patients who are at higher risk for more severe and distressing symptoms during CTX and to enable the initiation of preemptive symptom management interventions.

PURPOSE:Given the inter-relatedness among symptoms, research efforts are focused on an evaluation of symptom clusters. The purposes of this study were to evaluate for differences in the number and types of menopausal-related symptom clusters assessed prior to and at 12-months after surgery using ratings of occurrence and severity and to evaluate for changes in these symptom clusters over time. METHODS:Prior to and at 12 months after surgery, 392 women with breast cancer completed the Menopausal Symptoms Scale. Exploratory factor analyses were used to identify the symptom clusters. RESULTS:Of the 392 women evaluated, the mean number of symptoms (out of 46) was 13.2 (±8.5) at enrollment and 10.9 (±8.2) at 12 months after surgery. Using occurrence and severity, three symptom clusters were identified prior to surgery. Five symptom clusters were identified at 12 months following surgery. Two symptom clusters (i.e., pain/discomfort and hormonal) were relatively stable across both dimensions and time points. Two symptom clusters were relatively stable across both dimensions either prior to surgery (i.e., sleep/psychological/cognitive) or at 12 months after surgery (i.e., sleep). The other four clusters (i.e., irritability, psychological/cognitive, cognitive, psychological) were identified at one time point using a single dimension. CONCLUSIONS:While some menopausal-related symptom clusters were consistent across time and dimensions, the majority of symptoms clustered together differently depending on whether they were evaluated prior to or at 12 months after breast cancer surgery. An increased understanding of how symptom clusters change over time may assist clinicians to focus their symptom assessments and management strategies.

BackgroundIn mid-2016, Mozambique began phased implementation of the 'Test-and-Treat' policy, which enrolls HIV positive clients into antiretroviral treatment (ART) immediately regardless of CD4 cell count or disease stage. Novel insights into barriers and facilitators to ART initiation among healthy clients are needed to improve implementation of Test and Treat.Methods and findingsA cross-sectional qualitative study was conducted across 10 health facilities in Mozambique. In-depth interviews (IDIs) were conducted with HIV-positive clients (60 who initiated/20 who did not initiate ART within Test and Treat) and 9 focus group discussion (FGDs) were conducted with health care workers (HCWs; n = 53). Data were analyzed using deductive and inductive analysis strategies. Barriers to ART initiation included: (1) feeling 'healthy'; (2) not prepared to start ART for life; (3) concerns about ART side effects; (4) fear of HIV disclosure and discrimination; (5) poor interactions with HCWs; (6) limited privacy at health facilities; and (7) perceptions of long wait times. Facilitators included the motivation to stay healthy and to take care of dependents, as well as new models of ART services such as adaptation of counseling to clients' specific needs, efficient patient flow, and integrated HIV/primary care services.ConclusionsART initiation may be difficult for healthy clients in the context of Test-and-Treat. Specific strategies to engage this population are needed. Strategies could include targeted support for clients, community sensitization on the benefits of early ART initiation, client-centered approaches to patient care, and improved efficiency through multi-month scripting and increased workforce.

E-cigarettes are promoted as healthier alternatives to conventional cigarettes. Many cigarette smokers use both products. It is unknown whether the additional use of e-cigarettes among cigarette smokers (dual users) is associated with reduced exposure to tobacco-related health risks. Cross-sectional analysis was performed using baseline data from the Health eHeart Study, among English-speaking adults, mostly from the United States. Cigarette use (# cigarettes/day) and/or e-cigarette use (# days, # cartridges, and # puffs) were compared between cigarette only users vs. dual users. Additionally, we examined cardiopulmonary symptoms/ conditions across product use: no product (neither), e-cigarettes only, cigarettes only, and dual use. Among 39,747 participants, 573 (1.4%) reported e-cigarette only use, 1,693 (4.3%) reported cigarette only use, and 514 (1.3%) dual use. Dual users, compared to cigarette only users, reported a greater median (IQR) number of cigarettes per day, 10.0 (4.0-20.0) vs. 9.0 (3.0-15.0) (p < .0001), a lower (worse) median (IQR) SF-12 general health score, 3.3 (2.8-3.8) vs. 3.5 (2.8-3.9) (p = .0014), and a higher (worse) median (IQR) breathing difficulty score in the past month, 2.0 (1.0-2.0) vs. 1.0 (1.0-2.0) (p = .001). Of the 19 cardiopulmonary symptoms/ conditions, having a history of arrhythmia was significantly different between cigarette only users (14.2%) and dual users (17.8%) (p = .02). In this sample, dual use was not associated with reduced exposure to either (i) cigarettes, compared to cigarette only users or (ii) e-cigarettes, compared to e-cigarette only users. E-cigarette only use, compared to no product use, was associated with lower general health scores, higher breathing difficulty scores (typically and past month), and greater proportions of those who responded 'yes' to having chest pain, palpitations, coronary heart disease, arrhythmia, COPD, and asthma. These data suggest the added use of e-cigarettes alone may have contributed to cardiopulmonary health risks particularly respiratory health risks.

ContextAlthough physical function is an important patient outcome, little is known about changes in physical function in older adults receiving chemotherapy (CTX).ObjectivesIdentify subgroups of older patients based on changes in their level of physical function; determine which demographic and clinical characteristics were associated with subgroup membership; and determine if these subgroups differed on quality-of-life (QOL) outcomes.MethodsLatent profile analysis was used to identify groups of older oncology patients (n = 363) with distinct physical function profiles. Patients were assessed six times over two cycles of CTX using the Physical Component Summary score from the Short Form 12. Differences, among the groups, in demographic and clinical characteristics and QOL outcomes were evaluated using parametric and nonparametric tests.ResultsThree groups of older oncology patients with distinct functional profiles were identified: Well Below (20.4%), Below (43.8%), and Above (35.8%) normative Physical Component Summary scores. Characteristics associated with membership in the Well Below class included the following: lower annual income, a higher level of comorbidity, being diagnosed with depression and back pain, and lack of regular exercise. Compared with the Above class, patients in the other two classes had significantly poorer QOL outcomes.ConclusionAlmost 65% of older oncology patients reported significant decrements in physical function that persisted over two cycles of CTX. Clinicians can assess for those characteristics associated with poorer functional status to identify high-risk patients and initiate appropriate interventions.

PurposeIn a sample of outpatients with breast, gastrointestinal, gynecological, and lung cancer who received at least two cycles of chemotherapy (CTX), the purposes were to evaluate for inter-individual differences in the severity of sleep disturbance and determine which demographic, clinical, and symptom characteristics were associated with initial levels as well as the trajectories of sleep disturbance.MethodsA total of 1331 patients completed study questionnaires in their homes, at six time points over two cycles of CTX (prior to CTX administration, approximately 1 week after CTX administration, and approximately 2 weeks after CTX administration). Questionnaires included demographic, clinical, and symptom assessments (i.e., General Sleep Disturbance Scale, Lee Fatigue Scale, Center for Epidemiological Studies-Depression Scale, Spielberger State-Trait Anxiety Inventories, Attentional Function Index). Hierarchical linear modeling based on full maximum likelihood estimation was performed.ResultsCharacteristics associated with higher initial levels of sleep disturbance included higher body mass index, poorer functional status, higher trait anxiety, higher depressive symptoms, and higher evening fatigue. Characteristics associated with the worse trajectories of sleep disturbance were higher levels of education and higher sleep disturbance at enrollment. Characteristics associated with both higher initial levels and worse trajectories of sleep disturbance were higher morning fatigue and worse attentional function.ConclusionsA large amount of inter-individual variability exists in sleep disturbance during CTX. The modifiable and non-modifiable characteristics found in this study can be used to identify higher risk patients and provide earlier interventions to reduce sleep disturbance.

As the largest group of health professionals, nurses have a tremendous potential to help curb the tobacco epidemic. However, studies conducted across a range of global settings continue to indicate that both practicing nurses and nursing student have limited knowledge, skills and confidence needed to implement evidence-based tobacco cessation interventions. A contributing factor is the limited inclusion of tobacco control content in nursing curricula. Additionally, there is limited understanding of nurse educators' knowledge and perceptions about teaching tobacco dependence content. This paper presents the Loma Linda University School of Nursing's concurrent experience with both faculty development and curriculum redesign in the area of tobacco dependence prevention and treatment. An internal survey was administered at baseline and at 2-year follow-up to assess faculty's knowledge, perceptions and practices related to teaching tobacco dependence content and skills (n = 42). Faculty and curriculum development strategies and resources utilized, evaluation findings and subsequent lessons learned are described. The findings have implications for nursing programs seeking to enhance their curricula and commitment to ensuring that their graduates are prepared to provide evidence-based tobacco cessation interventions with each patient they encounter.

ObjectiveTo examine the relationship between spending on electronic cigarettes (e-cigarettes) and disease symptoms compared with the relationship between 30-day e-cigarette use and disease symptoms among adult cigarette smokers in the U.S.MethodsWe analyzed data from the Tobacco and Attitudes Beliefs Survey which included 533 respondents aged 24+ who were current cigarette smokers and e-cigarette ever users. Fifteen self-reported disease symptoms were included as outcome variables. Separate multivariable logistic regression models were estimated for each disease symptom with total spending on e-cigarettes in the past 30 days and with reported 30-day e-cigarette use. All models controlled for cigarettes smoked per day (CPD) and sociodemographic characteristics.ResultsWe found that those who spent more on e-cigarettes were more likely to report chest pain (AOR = 1.25, 95% CI 1.02-1.52), to notice blood when brushing their teeth (AOR = 1.23, 95% CI 1.02-1.49), to have sores or ulcers in their mouth (AOR = 1.36, 95% CI 1.08-1.72), and to have more than one cold (AOR = 1.36, 95% CI 1.05-1.78) than those with no spending on e-cigarettes in the past 30 days in an adjusted analysis. After controlling for CPD and other covariates, there were no significant relationships between 30-day e-cigarette use and symptoms. Even after controlling for CPD, e-cigarette expenditures or use was associated with greater odds of wheezing and shortness of breath.ConclusionsE-cigarette expenditures might be a more useful measure of intensity of e-cigarette use. The additional health effect of e-cigarette use or expenditures among smokers independent of the effect of CPD suggests that e-cigarette use adds adverse health effects even among cigarette smokers.

BackgroundPatients with colorectal cancer (CRC) rarely experience a single symptom associated with their disease and its treatment.ObjectivePurpose of this literature review was to summarize the current state of knowledge of multiple co-occurring symptoms in CRC patients who received chemotherapy (CTX) alone or CTX with targeted therapies.MethodsComprehensive literature search was conducted from 1990 to 2014. These studies were evaluated in terms of the occurrence of multiple co-occurring symptoms in CRC patients who received CTX alone or CTX with targeted therapies; the most common symptom assessment and quality of life (QOL) instruments used; and the associations identified between select demographic and treatment characteristics, QOL, and multiple co-occurring symptoms.ResultsOnly 5 studies met this review's inclusion criteria. Two studies compared symptoms in patients who received CTX alone or CTX with targeted therapies, and only 1 study reported on symptom occurrence. Of the 5 studies identified, only 2 used the same instrument to assess symptoms, and only 2 studies evaluated for associations between demographic and treatment characteristics and symptom burden, as well as QOL outcomes.ConclusionsGiven the larger number of patients with CRC, as well as the increased number of CRC patients who will receive targeted therapies with or without CTX, future studies need to describe the occurrence, severity, and distress of multiple co-occurring symptoms and their impact on CRC patients' QOL.Implications for practiceTo deliver effective symptom management interventions, the most common, severe, and distressing symptoms that CRC patients experience need to be identified.

BackgroundMedical marijuana legalization is associated with a higher prevalence of marijuana use which may affect cigarette use and nicotine dependence in co-users. In the present study, we examined relationships between statewide legalization of medical marijuana and prevalence of cigarette and marijuana co-use and nicotine dependence in co-using adolescents and adults.MethodsData were analyzed from the 2013 National Survey on Drug Use and Health. We compared cigarette and marijuana co-use in the past 30days across age categories (12-64 years) by statewide medical marijuana legalization. Logistic regression models were used to estimate the odds of having nicotine dependence among current cigarette smokers who also reported past 30-day marijuana use and "ever but not current" marijuana use (vs. "never" use) adjusting for covariates including statewide legalization of medical marijuana.ResultsOverall, 5.1% of the sample reported past 30-day cigarette and marijuana co-use and a higher proportion of co-users resided in states where medical marijuana was legal compared to illegal (5.8% vs. 4.8%; p=0.0011). Co-use was associated with greater odds of having nicotine dependence compared to cigarette-only use across age categories. Odds were highest and up to 3-times higher in adolescents aged 12-17 years (OR=3.54; 95%CI: 1.81-6.92) and adults aged 50-64 years (OR=3.08; CI: 1.45-6.55).ConclusionMarijuana policy could inadvertently affect cigarette and marijuana co-use and pose challenges to tobacco cessation.

The quality of cancer care may be compromised in the near future because of work force issues. Several factors will impact the oncology health provider work force: an aging population, an increase in the number of cancer survivors, and expansion of health care coverage for the previously uninsured. Between October 2014 and March 2015, an electronic literature search of English language articles was conducted using PubMed(®) , the Cumulative Index to Nursing and Allied Health Sciences (CINAHL(®) ), Web of Science, Journal Storage (JSTOR(®) ), Google Scholar, and SCOPUS(®) . Using the scoping review criteria, the research question was identified "How much care in oncology is provided by nurse practitioners (NPs)?" Key search terms were kept broad and included: "NP" AND "oncology" AND "workforce". The literature was searched between 2005 and 2015, using the inclusion and exclusion criteria, 29 studies were identified, further review resulted in 10 relevant studies that met all criteria. Results demonstrated that NPs are utilized in both inpatient and outpatient settings, across all malignancy types and in a variety of roles. Academic institutions were strongly represented in all relevant studies, a finding that may reflect the Accreditation Council for Graduate Medical Education (ACGME) duty work hour limitations. There was no pattern associated with state scope of practice and NP representation in this scoping review. Many of the studies reviewed relied on subjective information, or represented a very small number of NPs. There is an obvious need for an objective analysis of the amount of care provided by oncology NPs.

ObjectivesWe examined effects of long-term medical marijuana legalization on cigarette co-use in a sample of adults.MethodsWe conducted secondary analysis using data from the 2014 US Tobacco Attitudes and Beliefs Survey, which consisted of cigarette smokers, aged ≥ 45 years (N = 506). Participants were categorized by their state residence, where medical marijuana was (1) illegal, (2) legalized < 10 years, and (3) legalized ≥ 10 years. The Web-based survey assessed participants' marijuana use, beliefs and attitudes on marijuana, and nicotine dependence using Fagerstrom Tolerance for Nicotine Dependence (FTND) and Hooked on Nicotine Checklist (HONC) scores.ResultsIn cigarette smokers aged ≥ 45 years, long-term legalization of medical marijuana was associated with stable positive increases in marijuana use prevalence (ever in a lifetime) (p = .005) and frequency (number of days in past 30 days) (unadjusted p = .005; adjusted p = .08). Those who reported marijuana co-use had greater FTND and HONC scores after adjusting for covariates (p = .05).ConclusionsThese preliminary findings warrant further examination of the potential impact of long-term legalization of medical marijuana on greater cigarette and marijuana co-use in adults and higher nicotine dependence among co-users at the population level.

BackgroundLocal excision is an organ-preserving treatment alternative to transabdominal resection for patients with stage I rectal cancer. However, local excision alone is associated with a high risk of local recurrence and inferior survival compared with transabdominal rectal resection. We investigated the oncological and functional outcomes of neoadjuvant chemoradiotherapy and local excision for patients with stage T2N0 rectal cancer.MethodsWe did a multi-institutional, single-arm, open-label, non-randomised, phase 2 trial of patients with clinically staged T2N0 distal rectal cancer treated with neoadjuvant chemoradiotherapy at 26 American College of Surgeons Oncology Group institutions. Patients with clinical T2N0 rectal adenocarcinoma staged by endorectal ultrasound or endorectal coil MRI, measuring less than 4 cm in greatest diameter, involving less than 40% of the circumference of the rectum, located within 8 cm of the anal verge, and with an Eastern Cooperative Oncology Group performance status of at least 2 were included in the study. Neoadjuvant chemoradiotherapy consisted of capecitabine (original dose 825 mg/m(2) twice daily on days 1-14 and 22-35), oxaliplatin (50 mg/m(2) on weeks 1, 2, 4, and 5), and radiation (5 days a week at 1·8 Gy per day for 5 weeks to a dose of 45 Gy, followed by a boost of 9 Gy, for a total dose of 54 Gy) followed by local excision. Because of adverse events during chemoradiotherapy, the dose of capecitabine was reduced to 725 mg/m(2) twice-daily, 5 days per week, for 5 weeks, and the boost of radiation was reduced to 5·4 Gy, for a total dose of 50·4 Gy. The primary endpoint was 3-year disease-free survival for all eligible patients (intention-to-treat population) and for patients who completed chemotherapy and radiation, and had ypT0, ypT1, or ypT2 tumours, and negative resection margins (per-protocol group). This study is registered with ClinicalTrials.gov, number NCT00114231.FindingsBetween May 25, 2006, and Oct 22, 2009, 79 eligible patients were recruited to the trial and started neoadjuvant chemoradiotherapy. Two patients had no surgery and one had a total mesorectal excision. Four additional patients completed protocol treatment, but one had a positive margin and three had ypT3 tumours. Thus, the per-protocol population consisted of 72 patients. Median follow-up was 56 months (IQR 46-63) for all patients. The estimated 3-year disease-free survival for the intention-to-treat group was 88·2% (95% CI 81·3-95·8), and for the per-protocol group was 86·9% (79·3-95·3). Of 79 eligible patients, 23 (29%) had grade 3 gastrointestinal adverse events, 12 (15%) had grade 3-4 pain, and 12 (15%) had grade 3-4 haematological adverse events during chemoradiation. Of the 77 patients who had surgery, six (8%) had grade 3 pain, three (4%) had grade 3-4 haemorrhage, and three (4%) had gastrointestinal adverse events.InterpretationAlthough the observed 3-year disease free survival was not as high as anticipated, our data suggest that neoadjuvant chemoradiotherapy followed by local excision might be considered as an organ-preserving alternative in carefully selected patients with clinically staged T2N0 tumours who refuse, or are not candidates for, transabdominal resection.FundingNational Cancer Institute and Sanofi-Aventis.

Purpose/objectivesTo identify priority areas of research for the Oncology Nursing Society (ONS) Research Agenda for 2014-2018, consistent with ONS's mission to promote excellence in oncology nursing and quality cancer care
.Data sourcesReview of the literature, 2013 ONS Research Priorities Survey, National Institute of Nursing Research, and the National Cancer Institute research foci
.Data synthesisMultimethod consensus-building approach by content leaders and content experts of the ONS Research Agenda Project Team
.ConclusionsThe 2014-2018 Research Agenda Project Team identified eight high-priority research areas: symptoms, late effects of cancer treatment and survivorship care, palliative and end-of-life care, self-management, aging, family and caregivers, improving healthcare systems, and risk reduction. In addition, four cross-cutting themes were identified: biomarkers, bioinformatics, comparative effectiveness research, and dissemination and implementation science.Implications for nursingThe Research Agenda is a synthesis of the state of the science in cancer and identifies gaps and directions for the conduct and dissemination of research. Oncology nurses can use the agenda to inform clinical practice, develop research proposals, inform policy makers, support interdisciplinary research efforts, and promote scientist and clinician collaborations in targeted patient-centered research
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BACKGROUND: Patients with locally advanced rectal cancer who achieve a pathological complete response to neoadjuvant chemoradiation have an improved prognosis. The need for surgery in these patients has been questioned, but the proportion of patients achieving a pathological complete response is small. We aimed to assess whether adding cycles of mFOLFOX6 between chemoradiation and surgery increased the proportion of patients achieving a pathological complete response. METHODS: We did a phase 2, non-randomised trial consisting of four sequential study groups of patients with stage II-III locally advanced rectal cancer at 17 institutions in the USA and Canada. All patients received chemoradiation (fluorouracil 225 mg/m(2) per day by continuous infusion throughout radiotherapy, and 45·0 Gy in 25 fractions, 5 days per week for 5 weeks, followed by a minimum boost of 5·4 Gy). Patients in group 1 had total mesorectal excision 6-8 weeks after chemoradiation. Patients in groups 2-4 received two, four, or six cycles of mFOLFOX6, respectively, between chemoradiation and total mesorectal excision. Each cycle of mFOLFOX6 consisted of racemic leucovorin 200 mg/m(2) or 400 mg/m(2), according to the discretion of the treating investigator, oxaliplatin 85 mg/m(2) in a 2-h infusion, bolus fluorouracil 400 mg/m(2) on day 1, and a 46-h infusion of fluorouracil 2400 mg/m(2). The primary endpoint was the proportion of patients who achieved a pathological complete response, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00335816. FINDINGS: Between March 24, 2004, and Nov 16, 2012, 292 patients were registered, 259 of whom (60 in group 1, 67 in group 2, 67 in group 3, and 65 in group 4) met criteria for analysis. 11 (18%, 95% CI 10-30) of 60 patients in group 1, 17 (25%, 16-37) of 67 in group 2, 20 (30%, 19-42) of 67 in group 3, and 25 (38%, 27-51) of 65 in group 4 achieved a pathological complete response (p=0·0036). Study group was independently associated with pathological complete response (group 4 compared with group 1 odds ratio 3·49, 95% CI 1·39-8·75; p=0·011). In group 2, two (3%) of 67 patients had grade 3 adverse events associated with the neoadjuvant administration of mFOLFOX6 and one (1%) had a grade 4 adverse event; in group 3, 12 (18%) of 67 patients had grade 3 adverse events; in group 4, 18 (28%) of 65 patients had grade 3 adverse events and five (8%) had grade 4 adverse events. The most common grade 3 or higher adverse events associated with the neoadjuvant administration of mFOLFOX6 across groups 2-4 were neutropenia (five in group 3 and six in group 4) and lymphopenia (three in group 3 and four in group 4). Across all study groups, 25 grade 3 or worse surgery-related complications occurred (ten in group 1, five in group 2, three in group 3, and seven in group 4); the most common were pelvic abscesses (seven patients) and anastomotic leaks (seven patients). INTERPRETATION: Delivery of mFOLFOX6 after chemoradiation and before total mesorectal excision has the potential to increase the proportion of patients eligible for less invasive treatment strategies; this strategy is being tested in phase 3 clinical trials. FUNDING: National Institutes of Health National Cancer Institute.

Background and objectivesDe-normalization of smoking as a public health strategy may create shame and isolation in vulnerable groups unable to quit. To examine the nature and impact of smoking stigma, we developed the Internalized Stigma of Smoking Inventory (ISSI), tested its validity and reliability, and explored factors that may contribute to smoking stigma.MethodsWe evaluated the ISSI in a sample of smokers with mental health diagnoses (N = 956), using exploratory and confirmatory factor analysis, and assessed construct validity.ResultsResults reduced the ISSI to eight items with three subscales: smoking self-stigma related to shame, felt stigma related to social isolation, and discrimination experiences. Discrimination was the most commonly endorsed of the three subscales. A multivariate generalized linear model predicted 21-30% of the variance in the smoking stigma subscales. Self-stigma was greatest among those intending to quit; felt stigma was highest among those experiencing stigma in other domains, namely ethnicity and mental illness-based; and smoking-related discrimination was highest among women, Caucasians, and those with more education.Discussion and conclusionSmoking stigma may compound stigma experiences in other areas. Aspects of smoking stigma in the domains of shame, isolation, and discrimination were related to modeled stigma responses, particularly readiness to quit and cigarette addiction, and were found to be more salient for groups where tobacco use is least prevalent.Scientific significanceThe ISSI measure is useful for quantifying smoking-related stigma in multiple domains.

Purpose of the researchEvaluate for associations between variations in genes involved in catecholaminergic, gamma-aminobutyric acid (GABA)-ergic, and serotonergic mechanisms of neurotransmission and attentional function latent classes.Patients and methodsThis descriptive, longitudinal study was conducted at two radiation therapy departments. The sample included three latent classes of individuals with distinct trajectories of self-reported attentional function during radiation therapy, who were previously identified using growth mixture modeling among 167 oncology patients and 85 of their family caregivers. Multivariable models were used to evaluate for genotypic associations of neurotransmission genes with attentional function latent class membership, after controlling for covariates.ResultsVariations in catecholaminergic (i.e., ADRA1D rs4815675, SLC6A3 rs37022), GABAergic (i.e., SLC6A1 rs2697138), and serotonergic (i.e., HTR2A rs2296972, rs9534496) neurotransmission genes were significant predictors of latent class membership in multivariable models.ConclusionsFindings suggest that variations in genes that encode for three distinct but related neurotransmission systems are involved in alterations in attentional function. Knowledge of both phenotypic and genetic markers associated with alterations in attentional function can be used by clinicians to identify patients and family caregivers who are at higher risk for this symptom. Increased understanding of the genetic markers associated with alterations in attentional function may provide insights into the underlying mechanisms for this significant clinical problem.

ContextOlder oncology patients have unique needs associated with the many physical, psychological, and social changes associated with the aging process. The mechanisms underpinning and the impact of these changes are not well understood. Identification of clusters of symptoms is one approach that has been used to elicit hypotheses about the biological and/or psychological basis for variations in symptom experiences.ObjectivesThe purposes of this study were to identify and compare symptom clusters in younger (

ObjectivesTo describe older smokers' perceptions of risks and use of e-cigarettes, and their responses to marketing and knowledge of, and opinions about, regulation of e-cigarettes.MethodsEight 90-minute focus groups with 8 to 9 participants met in urban and suburban California to discuss topics related to cigarettes and alternative tobacco products.ResultsOlder adults are using e-cigarettes for cessation and as a way to circumvent no-smoking policies; they have false perceptions about the effectiveness and safety of e-cigarettes. They perceive e-cigarette marketing as a way to renormalize smoking.ConclusionsTo stem the current epidemic of nicotine addiction, the FDA must take immediate action because e-cigarette advertising promotes dual use and may contribute to the renormalization of smoking.

© 2015 Elsevier Ireland Ltd. Objective: To test the feasibility and usability of mHealth TLC, an interactive, immersive 3-dimensional iPad health game that coaches lung cancer patients toward assertive communication strategies during first-person virtual clinics visits. Method: We observed players and conducted semi-structured interviews. Research questions focused on scenario believability, the impact of technical issues, transparency of game goals, and potential of mHealth TLC to decrease lung cancer stigma (LCS) and improve patient-clinician communication. Results: Eight users confirmed mHealth TLC to be: (1) believable, (2) clinic-appropriate, and (3) helpful in support of informed healthcare consumers. Concerns were expressed about emotionally charged content and plans to use mHealth TLC in clinic settings as opposed to at home. Conclusions: Although the dialog and interactions addressed emotionally charged issues, players were able to engage, learn, and benefit from role-play in a virtual world. Health games have the potential to improve patient-clinician communication, and mHealth TLC specifically may decrease LCS, and promote optimal self-management. Practice implications: Process reflection revealed the need for health games to be created by experienced game developers in collaboration with health care experts. To prepare for this best practice, research institutions and game developers interested in health games should proactively seek out networking and collaboration opportunities.

PurposeAnxiety is common among cancer patients and their family caregivers (FCs) and is associated with poorer outcomes. Recently, associations between inflammation and anxiety were identified. However, the relationship between variations in cytokine genes and anxiety warrants investigation. Therefore, phenotypic and genotypic characteristics associated with trait and state anxiety were evaluated in a sample of 167 oncology patients with breast, prostate, lung, or brain cancer and 85 of their FCs.MethodsUsing multiple regression analyses, the associations between participants' demographic and clinical characteristics as well as variations in cytokine genes and trait and state anxiety were evaluated.ResultsIn the bivariate analyses, a number of phenotypic characteristics were associated with both trait and state anxiety (e.g., age, functional status). However, some associations were specific only to trait anxiety (e.g., number of comorbid conditions) or state anxiety (e.g., participation with a FC). Variations in three cytokine genes (i.e., interleukin (IL) 1 beta, IL1 receptor 2 (IL1R2), nuclear factor kappa beta 2 (NFKB2)) were associated with trait anxiety, and variations in two genes (i.e., IL1R2, tumor necrosis factor alpha (TNFA)) were associated with state anxiety.ConclusionsThese findings suggest that both trait and state anxiety need to be assessed in oncology patients and their FCs. Furthermore, variations in cytokine genes may contribute to higher levels of anxiety in oncology patients and their FCs.

The purpose of this study was to evaluate for differences in variations in pro- and anti-inflammatory cytokine genes between participants who were classified as having low and high levels of morning and evening fatigue and to evaluate for differences in phenotypic characteristics between these two groups. In a sample of 167 oncology outpatients with breast, prostate, lung, or brain cancer and 85 of their family caregivers, growth mixture modeling was used to identify latent classes of individuals based on ratings of morning and evening fatigue obtained prior to, during, and for 4 months following completion of radiation therapy. Differences in single nucleotide polymorphisms and haplotypes in 15 cytokine genes were evaluated between the latent classes. Multiple logistic regression was used to assess the effect of phenotypic and genotypic characteristics on morning and evening fatigue class membership. Associations were found between morning fatigue and number of comorbidities as well as variations in tumor necrosis factor alpha (TNFA) rs1800629 and rs3093662. Evening fatigue was associated with caring for children at home and variations in interleukin 4 (IL4) rs2243248 and TNFA rs2229094. Younger age and lower performance status were associated with both morning and evening fatigue. These findings suggest that inflammatory mediators are associated with the development of morning and evening fatigue. However, because different phenotypic characteristics and genomic markers are associated with diurnal variations in fatigue, morning and evening fatigue may be distinct but related symptoms.

The purpose of this study was to evaluate for differences in variations in pro- and anti-inflammatory cytokine genes between participants who were classified as having low and high levels of morning and evening fatigue and to evaluate for differences in phenotypic characteristics between these two groups. In a sample of 167 oncology outpatients with breast, prostate, lung, or brain cancer and 85 of their family caregivers, growth mixture modeling was used to identify latent classes of individuals based on ratings of morning and evening fatigue obtained prior to, during, and for 4 months following completion of radiation therapy. Differences in single nucleotide polymorphisms and haplotypes in 15 cytokine genes were evaluated between the latent classes. Multiple logistic regression was used to assess the effect of phenotypic and genotypic characteristics on morning and evening fatigue class membership. Associations were found between morning fatigue and number of comorbidities as well as variations in tumor necrosis factor alpha (TNFA) rs1800629 and rs3093662. Evening fatigue was associated with caring for children at home and variations in interleukin 4 (IL4) rs2243248 and TNFA rs2229094. Younger age and lower performance status were associated with both morning and evening fatigue. These findings suggest that inflammatory mediators are associated with the development of morning and evening fatigue. However, because different phenotypic characteristics and genomic markers are associated with diurnal variations in fatigue, morning and evening fatigue may be distinct but related symptoms.

PurposeThis study explored the relationships between variations in cytokines genes and depressive symptoms in a sample of patients who were assessed prior to and for six months following breast cancer surgery. Phenotypic differences between Resilient (n = 155) and Subsyndromal (n = 180) depressive symptom classes, as well as variations in cytokine genes were evaluated.MethodPatients were recruited prior to surgery and followed for six months. Growth mixture modeling was used to identify distinct latent classes based on Center for Epidemiological Studies Depression (CES-D) Scale scores. Eighty-two single nucleotide polymorphisms and 35 haplotypes among 15 candidate cytokine genes were evaluated.ResultsPatients in the Subsyndromal class were significantly younger, more likely to be married or partnered, and reported a significantly lower functional status. Variation in three cytokine genes (i.e., interferon gamma receptor 1 (IFNGR1 rs9376268), interleukin 6 (IL6 rs2069840), tumor necrosis factor alpha (TNFA rs1799964)), as well as age and functional status predicted membership in the Subsyndromal versus the Resilient class.ConclusionsA variation in TNFA that was associated with Subsyndromal depressive symptoms in a sample of patients and their family caregivers was confirmed in this sample. Variations in cytokine genes may place these patients at higher risk for the development of Subsyndromal levels of depressive symptoms.

PurposeThe presence of distant metastases is one of the most powerful predictors of outcome in patients with neuroblastoma. However, the pattern of metastatic spread is not incorporated into current risk stratification systems. Small case series have suggested that patients with neuroblastoma who have metastatic disease limited to distant lymph nodes (4N disease) may have improved outcomes.Patients and methodsWe analyzed retrospective data from the International Neuroblastoma Risk Group database for patients diagnosed from 1990 to 2002. 4N patients were compared with the remaining stage 4 patients (non-4N), excluding those with missing metastatic site data.ResultsIn all, 2,250 International Neuroblastoma Staging System stage 4 patients with complete data were identified, of whom 146 (6.5%) had 4N disease. For 4N patients, event-free survival (EFS; 5-year, 77% ± 4%) and overall survival (OS; 5-year, 85% ± 3%) were significantly better than EFS (5-year, 35% ± 1%) and OS (5-year, 42% ± 1%) for non-4N stage 4 patients (P < .001). 4N patients were more likely to be younger (P < .001) and have tumors with favorable characteristics, including absence of MYCN amplification (89% v 69%; P < .001). In a multivariable analysis, 4N disease remained a significant predictor of outcome (hazard ratio for non-4N v 4N: 3.40 for EFS and 3.69 for OS). Within subgroups defined by age at diagnosis and tumor MYCN status, 4N disease was significantly associated with improved outcomes.Conclusion4N represents a subgroup with better outcome than that of other patients with metastatic disease. These findings suggest that the biology and treatment response of 4N tumors differ from other stage 4 tumors, and less intensive therapy should be considered for this cohort. Future exploration of biologic factors determining the pattern of metastatic spread is warranted.

CONTEXT: The relatively low number of older patients in cancer trials limits knowledge of how older adults experience symptoms associated with cancer and its treatment. OBJECTIVES: This study evaluated for differences in the symptom experience across four older age groups (60-64, 65-69, 70-74, ≥75 years). METHODS: Demographic, clinical, and symptom data from 330 patients aged >60 years who participated in one Australian and two U.S. studies were evaluated. The Memorial Symptom Assessment Scale was used to evaluate the occurrence, severity, frequency, and distress of 32 symptoms commonly associated with cancer and its treatment. RESULTS: On average, regardless of the age group, patients reported 10 concurrent symptoms. The most prevalent symptoms were physical in nature. Worrying was the most common psychological symptom. For 28 (87.5%) of the 32 Memorial Symptom Assessment Scale symptoms, no age-related differences were found in symptom occurrence rates. For symptom severity ratings, an age-related trend was found for difficulty swallowing. As age increased, severity of difficulty swallowing decreased. For symptom frequency, age-related trends were found for feeling irritable and diarrhea, with both decreasing in frequency as age increased. For symptom distress, age-related trends were found for lack of energy, shortness of breath, feeling bloated, and difficulty swallowing. As age increased, these symptoms received lower average distress ratings. CONCLUSION: Additional research is warranted to examine how age differences in symptom experience are influenced by treatment differences, aging-related changes in biological or psychological processes, or age-related response shift.

Subgroups of individuals may be at greater risk of cytokine-induced changes in attentional function. The purposes of this study were to identify subgroups of individuals with distinct trajectories of attentional function and evaluate for phenotypic and genotypic (i.e., cytokine gene polymorphisms) differences among these subgroups. Self-reported attentional function was evaluated in 252 participants (167 oncology patients and 85 family caregivers) using the Attentional Function Index before radiation therapy and at six additional assessments over 6 months. Three latent classes of attentional function were identified using growth mixture modeling: moderate (36.5%), moderate-to-high (48.0%), and high (15.5%) attentional function. Participants in the moderate class were significantly younger, with more comorbidities and lower functional status, than those in the other two classes. However, only functional status remained significant in multivariable models. Included in the genetic association analyses were 92 single nucleotide polymorphisms (SNPs) among 15 candidate genes. Additive, dominant, and recessive genetic models were assessed for each SNP. Controlling for functional status, only Interleukin 6 (IL6) rs1800795 remained a significant genotypic predictor of class membership in multivariable models. Each additional copy of the rare G allele was associated with a 4-fold increase in the odds of belonging to the lower attentional function class (95% confidence interval: [1.78, 8.92]; p = .001). Findings provide preliminary evidence of subgroups of individuals with distinct trajectories of attentional function and of a genetic association with an IL6 promoter polymorphism.