Replicating dissemination and identifying mechanisms of implementation of an empirically supported treatment.

OBJECTIVE: Implementation research is needed in cancer control. Replication of the dissemination of empirically supported treatments (ESTs) is important as is the identification of mechanisms by which dissemination leads to implementation. Addressing these gaps, Study 1 (Cohorts 3-6, N = 104) tests for replication of a successful dissemination to community providers (Brothers et al., 2015; Cohorts 1-2; N = 62) and Study 2 (Cohorts 1-6) tests providers' changes on dissemination outcomes as mechanisms of EST usage. METHOD: The Biobehavioral Intervention (BBI), a psychological EST in cancer control, was disseminated to oncology mental health providers using manual provision, didactics, roleplays, and other strategies. Study 1 tested for pre/post changes in dissemination outcomes (BBI knowledge/skills and attitudes toward and self-efficacy to deliver ESTs/BBI) between cohorts (1-2 vs. 3-6) with repeated measures ANOVAs. In Study 2, the implementation outcome was providers' (N = 166) BBI usage with patients (percent treated). Structural equation models tested dissemination outcome changes as predictors of usage at 2- and 4-months. RESULTS: Study 1 replicated high dissemination outcomes and significant gains in BBI knowledge (p < .001) in Cohorts 3-6. Unlike Cohorts 1-2, significant gains were observed in self-efficacy (ps < .001) but not attitudes toward ESTs (p = .523) in Cohorts 3-6. In Study 2, gains in providers' self-efficacy (ps < .05) and EST attitudes (p = .008) predicted greater 2-month (58.4% ± 35.5%) and 4-month (66.2% ± 35.0%) usage of the BBI with patients, respectively. CONCLUSIONS: This is the only replication of a dissemination for a psychological EST in cancer control. Results reliably show disseminations enhancing providers' self-efficacy to use and positive attitudes toward ESTs as mechanisms for EST implementation. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Dissemination of an evidence-based treatment for cancer patients: training is the necessary first step.

Evidence-based psychological treatments (EBTs) for cancer patients have not been disseminated in part due to lack of available training. The biobehavioral intervention (BBI) is an EBT designed to alleviate cancer stress and enhance coping. The current study evaluates a training program and uses the Theory of Planned Behavior (TpB) to analyze factors related to intentions to implement BBI. Mental health providers (n = 62) attended a training for BBI. Attendees' supervisors (n = 40) were later surveyed. Repeated measure ANOVAs assessed change over time in knowledge gains, attitudes towards EBTs/BBI, and self-efficacy. Linear multiple regression analyses assessed relationships between these factors and implementation intentions. BBI knowledge and attitude scores increased from pre- to post-training (ps < 0.01). Significant predictors in the final model were BBI-specific attitudes and self-efficacy (ps < 0.05). The BBI training program was an effective dissemination vehicle. Intervention-specific attitudes and self-efficacy were key factors in predicting providers' implementation intentions.

Test of mindfulness and hope components in a psychological intervention for women with cancer recurrence.

OBJECTIVE: Psychological interventions can attenuate distress and enhance coping for those with an initial diagnosis of cancer, but there are few intervention options for individuals with cancer recurrence. To address this gap, we developed and tested a novel treatment combining Mindfulness, Hope Therapy, and biobehavioral components. METHOD: An uncontrolled, repeated measures design was used. Women (N = 32) with recurrent breast or gynecologic cancers were provided 20 treatment sessions in individual (n = 12) or group (n = 20) formats. On average, participants were middle aged (M = 58) and Caucasian (81%). Independent variables (i.e., hope and mindfulness) and psychological outcomes (i.e., depression, negative mood, worry, and symptoms of generalized anxiety disorder) were assessed pre-treatment and 2, 4, and 7 months later. Session-by-session therapy process (positive and negative affect, quality-of-life) and mechanism (use of intervention-specific skills) measures were also included. RESULTS: Distress, anxiety, and negative affect decreased, whereas positive affect and mental-health-related quality-of-life increased over the course of treatment, as demonstrated in mixed-effects models with the intent-to-treat sample. Both hope and mindfulness increased, and use of mindfulness skills was related to decreased anxiety. CONCLUSIONS: This treatment was feasible to deliver and was acceptable to patients. The trial serves as preliminary evidence for a multi-component intervention tailored to treat difficulties specific to recurrent cancer. The blending of the components was novel as well as theoretically and practically consistent. A gap in the literature is addressed, providing directions for testing interventions designed for patients coping with the continuing stressors and challenges of cancer recurrence.

Emotions and social relationships for breast and gynecologic patients: a qualitative study of coping with recurrence.

BACKGROUND: In contrast to the large literature on patients' coping with an initial diagnosis of cancer, there have been few quantitative or qualitative studies of patients coping with recurrence. A qualitative study was undertaken to aid in the development of a tailored intervention for these patients. METHODS: Individuals (N=35) receiving follow-up care for recurrent breast or gynecologic cancer at a university-affiliated cancer center participated in an individual or a group interview. Transcripts of interviews were analyzed using a coding format with two areas of emphasis. First, we focused on patients' emotions, as there is specificity between emotions and the corresponding ways in which individuals choose to manage them. Secondly, we considered the patients' social environments and relationships, as they too appear key in the adjustment to, and survival from, cancer. RESULTS: Patients identified notable differences in their responses to an initial diagnosis of cancer and their current ones to recurrence, including the following: (i) depressive symptoms being problematic; (ii) with the passing years and the women's own aging, there is shrinkage in the size of social networks; and (iii) additional losses come from social support erosion, arising from a) intentional distancing by social contacts, b) friends and family not understanding that cancer recurrence is a chronic illness, and/or c) patients stemming their support requests across time. CONCLUSION: The contribution of these findings to the selection of intervention strategies is discussed.

Psychological stress is associated with altered levels of myeloid-derived suppressor cells in breast cancer patients.

Our group has shown in a randomized clinical trial that psychological intervention to reduce stress in patients with stages II and III breast cancer led to enhanced immune function, fewer recurrences and improved overall survival. We hypothesized that patients with high levels of stress would have alterations in myeloid-derived suppressor cells (MDSC) compared to patients with lower stress. PBMC from 16 patients with high stress (n = 8) or with low stress (n = 8) after surgery as measured by the Impact of Event Scale (IES) questionnaire were evaluated for the presence of MDSC. Patients with higher IES scores had significantly elevated salivary cortisol levels (P = 0.013; 13 µg/dl vs. 9.74 µg/dl). Levels of IL-1Rα were also significantly elevated in the higher IES group (45.09 pg/ml vs. 97.16 pg/ml; P = 0.010). IP 10, G-CSF, and IL-6 were all higher in the high stress group although not to a significant degree. Flow cytometric analysis for CD33+/HLA-DR-neg/CD15+/CD11b+ MDSC revealed increased MDSC in patients with lower IES scores (P = 0.009). CD11b+/CD15+ cells constituted 9.4% of the CD33+/HLA DR-neg cell population in patients with high IES, vs. 27.3% in patients with low IES scores. Additional analyzes of the number of stressful events that affected the patients in addition to their cancer diagnosis revealed that this type of stress measure correlated with elevated levels of MDSC (P = 0.064). These data indicate the existence of a complex relationship between stress and immune function in breast cancer patients.

Biobehavioral, immune, and health benefits following recurrence for psychological intervention participants.

PURPOSE: A clinical trial was designed to test the hypothesis that a psychological intervention could reduce the risk of cancer recurrence. Newly diagnosed regional breast cancer patients (n = 227) were randomized to the intervention-with-assessment or the assessment-only arm. The intervention had positive psychological, social, immune, and health benefits, and after a median of 11 years the intervention arm was found to have reduced the risk of recurrence (hazard ratio, 0.55; P = 0.034). In follow-up, we hypothesized that the intervention arm might also show longer survival after recurrence. If observed, we then would examine potential biobehavioral mechanisms. EXPERIMENTAL DESIGN: All patients were followed; 62 recurred. Survival analyses included all 62. Upon recurrence diagnosis, those available for further biobehavioral study were accrued (n = 41, 23 intervention and 18 assessment). For those 41, psychological, social, adherence, health, and immune (natural killer cell cytotoxicity, T-cell proliferation) data were collected at recurrence diagnosis and 4, 8, and 12 months later. RESULTS: Intent-to-treat analysis revealed reduced risk of death following recurrence for the intervention arm (hazard ratio, 0.41; P = 0.014). Mixed-effects follow-up analyses with biobehavioral data showed that all patients responded with significant psychological distress at recurrence diagnosis, but thereafter only the intervention arm improved (P values < 0.023). Immune indices were significantly higher for the intervention arm at 12 months (P values < 0.017). CONCLUSIONS: Hazards analyses augment previous findings in showing improved survival for the intervention arm after recurrence. Follow-up analyses showing biobehavioral advantages for the intervention arm contribute to our understanding of how improved survival was achieved.

The pain, depression, and fatigue symptom cluster in advanced breast cancer: covariation with the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system.

OBJECTIVE: Neuroendocrine-immune models have been proposed to account for the frequent co-occurrence of pain, depression, and fatigue (PDF) among cancer patients. DESIGN: In a cross-sectional observational study of advanced cancer patients (N = 104), we tested the hypothesis that the PDF cluster covaries with proposed biological mediators: hormones of the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis. MAIN OUTCOME MEASURES: PDF symptoms were measured using the Brief Pain Inventory, Fatigue Symptom Inventory, and the Center for Epidemiological Studies Depression scales. HPA activation was indicated by plasma levels of cortisol and adrenocorticotropic hormone, and SNS activation was indicated by plasma epinephrine and norepinephrine. RESULTS: Preliminary analyses supported the use of covariance structure modeling to test whether shared variance among hormone levels predicted shared variance among PDF symptoms. Latent variable analysis indicated that neuroendocrine levels predicted PDF (standardized beta = .23, p = .039), while controlling for important disease and demographic variables. CONCLUSION: Previous studies have linked individual symptoms to individual biomarkers. The observed significant paring of the 4 hormones to the PDF cluster provides the first evidence suggestive of stress hormones as a common mechanism for the co-occurrence of pain, depression, and fatigue symptoms.

A psychological intervention reduces inflammatory markers by alleviating depressive symptoms: secondary analysis of a randomized controlled trial.

OBJECTIVES: To test experimentally whether a psychological intervention reduces depression-related symptoms and markers of inflammation among cancer patients and to test one mechanism for the intervention effects. Depression and inflammation are common among cancer patients. Data suggest that inflammation can contribute to depressive symptoms, although the converse remains untested. METHODS: As part of a randomized clinical trial, newly diagnosed breast cancer patients (n = 45) with clinically significant depressive symptoms were evaluated and randomized to psychological intervention with assessment or assessment only study arms. The intervention spanned 12 months, with assessments at baseline, 4, 8, and 12 months. Mixed-effects modeling tested the hypothesis that the intervention reduced self-reported depressive symptoms (Center for Epidemiological Studies Depression scale, Profile of Mood States Depression and Fatigue subscales, and Medical Outcomes Study-Short Form 36 Bodily Pain subscale) and immune cell numbers that are elevated in the presence of inflammation (white blood cell count, neutrophil count, and helper/suppressor ratio). Mediation analyses tested whether change in depressive symptoms, pain, or fatigue predicted change in white blood cell count, neutrophil count, or the helper/suppressor ratio. RESULTS: The intervention reduced significantly depressive symptoms, pain, fatigue, and inflammation markers. Moreover, the intervention effect on inflammation was mediated by its effect on depressive symptoms. CONCLUSIONS: This is the first experiment to test whether psychological treatment effective in reducing depressive symptoms would also reduce indicators of inflammation. Data show that the intervention reduced directly depressive symptoms and reduced indirectly inflammation. Psychological treatment may treat effectively depressive symptoms, pain, and fatigue among cancer patients.

Psychologic intervention improves survival for breast cancer patients: a randomized clinical trial.

BACKGROUND: The question of whether stress poses a risk for cancer progression has been difficult to answer. A randomized clinical trial tested the hypothesis that cancer patients coping with their recent diagnosis but receiving a psychologic intervention would have improved survival compared with patients who were only assessed. METHODS: A total of 227 patients who were surgically treated for regional breast cancer participated. Before beginning adjuvant cancer therapies, patients were assessed with psychologic and behavioral measures and had a health evaluation, and a 60-mL blood sample was drawn. Patients were randomized to Psychologic Intervention plus assessment or Assessment only study arms. The intervention was psychologist led; conducted in small groups; and included strategies to reduce stress, improve mood, alter health behaviors, and maintain adherence to cancer treatment and care. Earlier articles demonstrated that, compared with the Assessment arm, the Intervention arm improved across all of the latter secondary outcomes. Immunity was also enhanced. RESULTS: After a median of 11 years of follow-up, disease recurrence was reported to occur in 62 of 212 (29%) women and death was reported for 54 of 227 (24%) women. Using Cox proportional hazards analysis, multivariate comparison of survival was conducted. As predicted, patients in the Intervention arm were found to have a reduced risk of breast cancer recurrence (hazards ratio [HR] of 0.55; P = .034) and death from breast cancer (HR of 0.44; P = .016) compared with patients in the Assessment only arm. Follow-up analyses also demonstrated that Intervention patients had a reduced risk of death from all causes (HR of 0.51; P = .028). CONCLUSIONS: Psychologic interventions as delivered and studied here can improve survival.

Delayed emotional recovery after taxane-based chemotherapy.

BACKGROUND: There are few patient-reported data regarding quality of life after taxane-based adjuvant chemotherapy and none regarding mental health outcomes. METHODS: This was a naturalistic, longitudinal study that used a case-control design. Data were derived from a randomized clinical trial in patients who had stage II/III breast cancer (N = 227). Paclitaxel (Taxol) was approved for use midway during the accrual period (1994-1999). Patients who received taxanes as part of their adjuvant chemotherapy (the taxane group; n = 55) were matched with patients receiving regimens without taxanes (the no-taxane group; n = 83) on trial arm, lymph node status, surgery type, menopausal status, and partner status. Mixed-effects models tested for group differences in nurse evaluations of patients' symptoms and Karnofsky performance status and in patient-reported quality of life (the 36-item Medical Outcomes Study Short Form) and emotional distress (Profile of Mood States; Center for Epidemiological Studies Depression scale). RESULTS: As expected, patients in the taxane group experienced significantly higher rates of selected toxicities, including arthralgia/myalgia (45% vs 26%) and ataxia (20% vs 5%). Patients in the taxane group also had significantly worse emotional distress and mental quality of life throughout adjuvant treatment. Rates of probable clinical depression also were high. In contrast, these outcomes were improving for patients in the no-taxane group (all P < .023). Emotional recovery for patients in the taxane group required 2 years on average versus 6 to 12 months for patients in the no-taxane group. During Years 3 through 5, the groups had similar outcomes. CONCLUSIONS: These data suggested that taxane-based chemotherapies confer risk for significant psychological symptoms. Depression, in particular, should be monitored.

Immune, endocrine, and behavioral precursors to breast cancer recurrence: a case-control analysis.

BACKGROUND: A period of tumor growth precedes the clinical detection of breast cancer recurrence. We explore immune, endocrine, and behavioral parameters during this period. METHODS: We conducted a phase III clinical trial in which women with surgically treated stage II/III breast cancer (N = 227) were randomized to receive a psychological intervention or assessment-only and then regularly assessed for 10 years. Patients who recurred (R, n = 48) were matched with patients remaining disease-free (DF, n = 48) on demographic and prognostic characteristics, treatment, and duration of disease-free follow-up. Data at three assessment points, occurring, on average, 17, 11, and 4 months before the recurrence was detected clinically, with equivalent time points for the disease-free group, were examined. Mixed-effects models tested for group differences in immune cell counts and function as well as endocrine and behavioral parameters. RESULTS: In the 17 months prior to recurrence detection, patients exhibited higher white blood cell count, neutrophil, lymphocyte, and natural killer cell counts, relative to DF patients. R patients also showed higher cortisol, worse physical functioning, fatigue, and quality of life. Follow-up analyses showed patients with local recurrences to differ from those with distant recurrence, with the former exhibiting elevated natural killer cell cytotoxicity, lymphocyte proliferative response, fatigue, pain, and emotional distress (depression, anxiety), and the latter exhibiting higher neutrophil, lymphocyte, and natural killer cell counts. CONCLUSION: Patients who would recur showed reliable biobehavioral alterations more than a year prior to their diagnosis. This novel observation may contribute to our understanding of the disease relapse processes.

Surviving recurrence: psychological and quality-of-life recovery.

BACKGROUND: To the authors' knowledge, data characterizing patients' psychosocial experiences after a recurrence diagnosis are limited. This report provides the physical, psychological, and quality-of-life trajectories of patients with recurrent breast cancer. In addition, patients with a well-documented trajectory -- patients with their initial diagnosis of breast cancer -- were included as a referent group, providing a metric against which to gauge the impact and course of cancer recurrence. METHODS: Patients with a newly diagnosed, recurrent (n = 69) or initial (n = 113) breast cancer were accrued. The groups did not differ with regard to age, race, education, family income, or partner status (all P values > .18). All patients were assessed shortly after diagnosis (baseline) and 4 months, 8 months, and 12 months later. Mixed-effects models were used to determine health status, stress, mood, and quality-of-life trajectories. RESULTS: In the year after a recurrence diagnosis, patients' physical health and functioning showed no improvement, whereas quality of life and mood generally improved, and stress declined. Compared with patients who were coping with their first diagnosis, patients with recurrence had significantly lower anxiety and confusion. In contrast, physical functioning was poorer among recurrence patients, quality-of-life improvement was slower, and cancer-related distress was high as that of the initially diagnosed patient. Slower quality-of-life recovery was most apparent among younger patients (aged <54 years). CONCLUSIONS: Despite the physical burden, patients with recurrent breast cancer exhibit considerable resilience, with steady improvements in psychological adjustment and quality of life during the year after diagnosis. Management of patients' physical symptoms is particularly important, because patients cope with recurrent breast cancer as a chronic illness.

Individual trajectories in stress covary with immunity during recovery from cancer diagnosis and treatments.

Research connects stressful events with altered immune regulation, but the role of subjective stress is uncertain. Using a longitudinal design, we provide a statistically powerful test of the relationship between subjective stress (perceived stress, emotional distress) and immunity (T cell blastogenesis, natural killer cell cytotoxicity, [NKCC]) as individuals adjust to a severe stressor, a cancer diagnosis and its treatments. Women with regional breast cancer (N=113) were assessed at diagnosis/surgery and reassessed 4, 8, 12, and 18 months later. Latent growth curve analysis tested two hypotheses: (1) initial levels of subjective stress will correlate inversely with initial levels of immunity, and (2) rate of change in subjective stress will correlate inversely with rate of change in immunity. As predicted by Hypothesis 1, participants with high initial subjective stress showed poor initial blastogenesis. As predicted by Hypothesis 2, participants exhibiting an early, rapid decline in subjective stress also showed rapid improvement in NKCC. Follow-up analyses revealed perceived stress to be strongly related to immune function, while emotional distress was not. This is the first study to investigate trajectories in stress and immunity during recovery from a major stressor. Results imply that NK and T cells are sensitive to different aspects of the stress response. While T cell blastogenesis correlated with initial (peak) subjective stress, NKCC correlated with change (improvement) in subjective stress. These data highlight the importance of subjective stress, particularly stress appraisals, in the immune response to a major stressor.

Traumatic stress, perceived global stress, and life events: prospectively predicting quality of life in breast cancer patients.

The authors investigated the relationship between stress at initial cancer diagnosis and treatment and subsequent quality of life (QoL). Women (n = 112) randomized to the assessment-only arm of a clinical trial were initially assessed after breast cancer diagnosis and surgery and then reassessed at 4 months (during adjuvant treatment) and 12 months (postadjuvant treatment). There were 3 types of stress measured: number of stressful life events (K. A. Matthews et al., 1997), cancer-related traumatic stress symptoms (M. J. Horowitz, N. Wilner, & W. Alvarez, 1979), and perceived global stress (S. Cohen, T. Kamarck, & R. Mermelstein, 1983). Using hierarchical multiple regressions, the authors found that stress predicted both psychological and physical QoL (J. E. Ware, K. K. Snow, & M. Kosinski, 2000) at the follow-ups (all ps < .03). These findings substantiate the relationship between initial stress and later QoL and underscore the need for timely psychological intervention.

Cellular immunity in breast cancer patients completing taxane treatment.

PURPOSE: A field study of postchemotherapy immune functioning relative to the use of taxanes is reported. Immune responses in breast cancer patients were analyzed as a function of whether patients received taxane as part of their adjuvant chemotherapy. EXPERIMENTAL DESIGN: Immune levels of 227 stage II/III breast cancer patients were measured immediately after surgery prior to chemotherapy and again 12 months later when all chemotherapies had been completed. T-cell blastogenesis and natural killer (NK) cell lysis levels of patients receiving taxanes (n = 55) were compared with levels of patients not receiving taxanes (n = 172). RESULTS: Regression analyses were conducted. The administration of taxane as part of combination chemotherapy predicted increased T-cell blastogenesis and NK cell cytotoxicity after the conclusion of all chemotherapies. For the Taxane group, average phytohemagglutinin-induced blastogenesis was 37% higher and NK cell cytotoxicity was 39% higher than the values for the No-Taxane group. CONCLUSIONS: Data from group comparisons with appropriate controls in a sizable clinical sample contravene traditional wisdom that taxanes suppress patients' immune cell functions. Problems in generalizing direct-contact laboratory models to the field of cancer treatment are highlighted.

Cardiovascular stress responses among Asian Indian and European American women and men.

Asian Indians have approximately 3 times the rate of coronary artery disease as do age-matched European Americans, but the increased risk cannot be explained by the presence of known physiological and behavioral risk factors. One previous study suggested that Asian Indians have diminished vasoactive responses to isoproterenol, but no published study has examined responses to psychological stressors. The purpose of this study was to test the hypothesis that the vasomotor response to stress, as indexed by hemodynamic measures, would be exaggerated in Asian Indian men and women, relative to European American individuals. Thirty-seven Asian Indian and 43 European American men and women were tested in a standard reactivity protocol, whereas heart rate, blood pressure, and cardiac impedance measures were assessed. Asian Indian men and women had significantly smaller changes in systolic blood pressure and mean arterial pressure during the stressors, relative to European American men and women. Asian Indian women, but not men, had significantly smaller diastolic blood pressure and total peripheral-resistance index changes to the stressors, relative to the other 3 groups. These data are in contrast to our expectation of decreased tendency of Asian Indians to vasodilate during psychological stress but do suggest that sex and Asian Indian ethnicity interact to influence vascular reactivity to stressors.