Implementation science and psycho-oncology: Advancing the translation of evidence into practice.

OBJECTIVES: This Special issue of Psycho-Oncology highlights examples of the application of implementation science to research in psycho-oncology. The aim is to demonstrate the different ways that implementation science is being used to generate evidence that can more readily translate evidence into changes in clinical practice. We hope this issue fosters greater interest in using the tools of implementation science to improve the lives of people affected by cancer. METHODS: The papers in the issue were selected from among those that responded to a call for submissions on the application of implementation science frameworks and methods to issues in psycho-oncology. The focus included but was not limited to research on: understanding barriers and facilitators of intervention/practice adoption; assessing implementation outcomes, evaluating implementation strategies, and improving behavioural and/or clinical outcomes. RESULTS: The 11 papers in this issue were grouped for presentation purposes into four common topics: barriers and facilitators to implementation; feasibility as a key implementation outcome; the design, selection and adaptation of implementation strategies; and building the foundation for psycho-oncology research translation via systematic reviews that focus on implementation strategy design. CONCLUSION: These papers demonstrate the breadth of current applications of implementation science to research in psycho-oncology. Alongside the studies featured in this issue, including cost-effectiveness analyses, tests of nationally-focused strategies and proactive planning for adaptation, we look forward to other innovations that will promote further growth of both disciplines to improve the integration of psycho-oncology interventions across healthcare systems.

Financial toxicity among people with metastatic cancer: findings from the Cancer Experience Registry.

PURPOSE: This study describes financial toxicity (FT) reported by people with metastatic cancer, characteristics associated with FT, and associations between FT and compensatory strategies to offset costs. METHODS: Cancer Support Community's Cancer Experience Registry data was used to identify respondents with a solid tumor metastatic cancer who completed the Functional Assessment of Chronic Illness Therapy COmprehensive Score for Financial Toxicity (FACIT-COST) measure. Multivariable logistic regression analyses examined associations between respondent characteristics and FT, and FT and postponing medical visits, nonadherence to medications, and postponing supportive and/or psychosocial care. RESULTS: 484 individuals were included in the analysis; the most common cancers included metastatic breast (31%), lung (13%), gynecologic (10%), and colorectal (9%). Approximately half of participants (50.2%) reported some degree of FT. Those who were non-Hispanic White, Hispanic, or multiple races (compared to non-Hispanic Black), and who reported lower income, less education, and being less than one year since their cancer diagnosis had greater odds of reporting FT. Individuals with any level of FT were also more likely to report postponing medical visits (Adjusted Odds Ratio [OR] 2.58; 95% Confidence Interval [CI] 1.45-4.58), suboptimal medication adherence (Adjusted OR 5.05; 95% CI 2.77-9.20) and postponing supportive care and/or psychosocial support services (Adjusted OR 4.16; 95% CI 2.53-6.85) compared to those without FT. CONCLUSIONS: With increases in the number of people living longer with metastatic cancer and the rising costs of therapy, there will continue to be a need to systematically screen and intervene to prevent and mitigate FT for these survivors.

Plasma levels of interleukin-6 mediate neurocognitive performance in older breast cancer survivors: The Thinking and Living With Cancer study.

BACKGROUND: Immune activation/inflammation markers (immune markers) were tested to explain differences in neurocognition among older breast cancer survivors versus noncancer controls. METHODS: Women >60 years old with primary breast cancer (stages 0-III) (n = 400) were assessed before systemic therapy with frequency-matched controls (n = 329) and followed annually to 60 months; blood was collected during annual assessments from 2016 to 2020. Neurocognition was measured by tests of attention, processing speed, and executive function (APE). Plasma levels of interleukin-6 (IL-6), IL-8, IL-10, tumor necrosis factor α (TNF-α), and interferon γ were determined using multiplex testing. Mixed linear models were used to compare results of immune marker levels by survivor/control group by time and by controlling for age, racial/ethnic group, cognitive reserve, and study site. Covariate-adjusted multilevel mediation analyses tested whether survivor/control group effects on cognition were explained by immune markers; secondary analyses examined the impact of additional covariates (e.g., comorbidity and obesity) on mediation effects. RESULTS: Participants were aged 60-90 years (mean, 67.7 years). Most survivors had stage I (60.9%) estrogen receptor-positive tumors (87.6%). Survivors had significantly higher IL-6 levels than controls before systemic therapy and at 12, 24, and 60 months (p ≤ .001-.014) but there were no differences for other markers. Survivors had lower adjusted APE scores than controls (p < .05). Levels of IL-6, IL-10, and TNF-α were related to APE, with IL-6 explaining part of the relationship between survivor/control group and APE (p = .01). The magnitude of this mediation effect decreased but remained significant (p = .047) after the consideration of additional covariates. CONCLUSIONS: Older breast cancer survivors had worse long-term neurocognitive performance than controls, and this relationship was explained in part by elevated IL-6.

Associations of Germline Genetic Variants With Depression and Fatigue Among Hematologic Cancer Patients Treated With Allogeneic Hematopoietic Cell Transplantation.

OBJECTIVE: Depression and fatigue are common among cancer patients and are associated with germline genetic variation. The goal of this pilot study was to examine genetic associations with depression and fatigue in the year after allogeneic hematopoietic cell transplant (HCT). METHODS: Blood was collected from patients and their donors before HCT. Patients completed self-report measures of depression and fatigue before HCT (T1), 90 days post-HCT (T2), and 1 year post-HCT (T3). Of the 384 genetic variants genotyped on a custom Illumina BeadChip microarray, 267 were retained for analysis based on quality control. Main effects of patient and donor variants as well as their interaction were examined using regression analyses. Significant variants were defined as those with a false discovery rate-adjusted p value of <.05. RESULTS: The sample consisted of 59 patient-donor pairs. Mean levels of depression and fatigue did not change significantly over time ( p values of > .41). Increases in depression from T1 to T2 were associated with patient-donor interactions at rs1928040 ( p = 3.0 × 10 -4 ) and rs6311 ( p = 2.0 × 10 -4 ) in HTR2A . Increases in fatigue from T1 to T2 were associated with patient rs689021 in SORL1 ( p = 6.0 × 10 -5 ) and a patient-donor interaction at rs1885884 in HTR2A ( p < 1.0 × 10 -4 ). CONCLUSIONS: Data suggest that variants in genes regulating the serotonergic system ( HTR2A ) and lipid metabolism ( SORL1 ) are associated with changes in depression and fatigue in allogeneic HCT patients, implicating patients' own genetic inheritance as well as that of donors. Additional studies are warranted to confirm these findings.

Psychosocial care for cancer survivors: A global review of national cancer control plans.

OBJECTIVE: National Cancer Control Plans (NCCPs) are high-level policy documents that prioritise actions to be taken to improve cancer control activities. As the number of cancer survivors grows globally, there is an urgent need to assess whether and how psychosocial care across the cancer care continuum is included in NCCPs. This review aimed to ascertain the extent to which NCCPs referenced psycho-oncology care for cancer survivors in the post-treatment phase. METHODS: NCCPs were obtained from the International Cancer Control Partnership (ICCP) portal (in November 2021) and reviewed in two phases. In Phase 1, all available NCCPs were screened to determine whether they mentioned psycho-oncology or survivorship. In Phase 2, reviewers extracted data from the NCCPs identified in Phase 1 on the degree that each plan articulated objectives/goals to improve psychosocial care in the post-treatment survivorship phase. RESULTS: We screened 237 NCCPs. Of these, initial potential reference to psycho-oncology and survivorship content were identified in 97 plans (41%). In Phase 1, 57/97 (59%) had reference to psycho-oncology or survivorship content within defined criteria. In Phase 2, 27/97 (28%) had little mention of psycho-oncology specifically in survivorship, 47/97 (48%) had some (general or brief) mention, and the remaining 23/97 (24%) had substantial content/specific sections and clearly articulated goals and/or objectives. Common goals for improving psychosocial care in the post-treatment period included building capacity of healthcare professionals, implementing rehabilitation models, and increasing the utilisation of community services. CONCLUSIONS: Most NCCPs did not reference psycho-oncology and only one-quarter contained clear objectives specifically in the post-treatment survivorship phase.

An Examination of the Longitudinal Relationship Between Cognitive Function and Physical Activity Among Older Breast Cancer Survivors in the Thinking and Living With Cancer Study.

BACKGROUND: Older cancer survivors are at risk for cognitive decline. Physical activity can improve cognition, and better cognitive function may facilitate greater physical activity. PURPOSE: We examined the potential bidirectional relationship between cognitive function and physical activity in older breast cancer survivors and controls. METHODS: The sample included women with newly diagnosed, nonmetastatic breast cancer (n = 395) and women without cancer (n = 374) ages 60-98. Participants were recruited as part of a larger multisite study, assessed prior to systemic therapy, and followed yearly for 36 months. Attention, processing speed, and executive function was measured using six neuropsychological tests, self-reported cognitive function using the Perceived Cognitive Impairments subscale of the Functional Assessment of Cancer Therapy-Cognitive Function , and physical activity using the International Physical Activity Questionnaire-Short Form. Separate random intercepts cross-lagged panel models were used to examine the between- and within-person effects for survivors and controls, controlling for age, education, and study site. RESULTS: Survivors reported significantly less physical activity than controls at baseline (1,284.92 vs. 2,085.98 MET min/week, p < .05). When survivors reported higher activity, they simultaneously had better objective cognition at 12 months (ß = 0.24, p = .04) and reported better perceived cognition at 12 and 24 months (ß = 0.25, p = .03), but this relationship was not seen in controls. Cognition did not predict subsequent physical activity or vice versa in either group. CONCLUSIONS: Cognition and physical activity are cross-sectionally associated in survivors, but the expected prospective relationships were not found.

Physical activity may improve cognitive function for older cancer survivors; however, cognitive function may also affect the ability to organize oneself to be physically active. We examined this potential bidirectional relationship in a sample of 395 women with newly diagnosed, nonmetastatic breast cancer, and 374 noncancer controls. These women completed cognitive tests and surveys yearly for 36 months. Surveys included their subjective cognitive function and physical activity. We examined the relationships between cognitive function (both objective and subjective) and physical activity over time (baseline, 12, 24, and 36 months). We found that when cancer survivors reported higher physical activity, they had better objective cognitive function at 12 months, and they reported better subjective cognitive function at 12 and 24 months. However, physical activity did not predict cognitive function at later time points, and cognitive function did not predict physical activity at later time points. In controls, better subjective cognitive function was related to higher physical activity overall, but there were not relationships over time or at specific time points. This was an observational study; therefore, future research should consider the potential impact of cognitive function when older cancer survivors are attempting to increase their physical activity.

Goals and goal perceptions in patients with advanced stage lung cancer: a mixed methods study.

PURPOSE: Goals provide insight into what is important to an individual. We describe the development and application of a mixed methods approach to elicit goals and perceptions about goals in patients with advanced cancer. METHODS: Patients receiving first-line treatment for advanced lung cancer participated in semi-structured interviews about their goals. Participants self-generated goals, then selected and ranked their three most important goals and provided Likert scale ratings of goal-related perceptions (e.g., attainability, locus of control). Independent raters coded goals into content domains. One month later, participants reported perceived progress toward goals and facilitators of and barriers to progress. RESULTS: Participants (N = 75, Mage = 64.5 years, 59% female) identified goals across eight domains: social/role/relationship, everyday/practical, leisure/pleasure, psychological/existential/spiritual, major life changes or achievements, cancer treatment response/disease outcomes, palliative outcomes, and behavioral health improvement. Of all goals identified (N = 352), 72% of patients had at least one social/role/relationship goal, 68% had a leisure/pleasure goal, and 29% had a cancer treatment response goal. On average, participants considered their goals to be attainable, perceived a high degree of control over reaching goals, anticipated making "some" progress in the short term, and perceived a high likelihood of reaching goals in the future. Facilitators of progress included mental fortitude, feeling physically well, and social support. Barriers included cancer-related side effects, practical challenges, and COVID-19. CONCLUSIONS: A majority of participant goals focused on meaningful engagement and living well. Goals were largely viewed as attainable and under participants' control. Cancer clinicians may consider how to support patients in working toward valued goals in conjunction with oncology care.

Identifying and describing cancer survivors: Implications for cancer survivorship research and clinical care.

BACKGROUND: Gathering information directly from cancer survivors has advanced our understanding of the cancer survivorship experience. However, it is unknown whether surveys can distinguish important subgroups of cancer survivors. This study aimed to describe the current landscape of survey questions used to identify and describe cancer survivors in national cross-sectional studies. METHODS: Using publicly available databases, the authors identified national cross-sectional surveys used in the United States within the past 15 years that included a question on self-reported history of cancer. After abstracting questions and response items used to identify cancer survivors, they conducted a descriptive analysis. RESULTS: The authors identified 14 national cross-sectional surveys, with half administered to the general population and the other half administered to cancer survivors. The most common question used to identify cancer survivors was "Have you ever been told by a doctor or other health professional that you had cancer?" Most surveys had questions asking participants to identify a single cancer type (n = 11), multiple prior cancer diagnoses or types (n = 11), and the time from diagnosis (n = 12). Treatment questions varied from active treatment status to specific treatments received. Questions addressing cancer stage (n = 2), subtypes (n = 1), metastatic status (n = 3), and recurrence (n = 4) were less frequently included. CONCLUSIONS: There is no standard method for assessing self-reported cancer history, and this limits the ability to distinguish among potentially important subgroups of survivors. Future cross-sectional surveys that capture nuanced data elements, such as cancer types, stages/subtypes, metastatic/recurrent status, and treatments received, can help to fill important gaps in cancer survivorship research and clinical care.

Association of markers of tumor aggressivity and cognition in women with breast cancer before adjuvant treatment: The Thinking and Living with Cancer Study.

PURPOSE: Tumor features associated with aggressive cancers may affect cognition prior to systemic therapy. We evaluated associations of cognition prior to adjuvant therapy and tumor aggressivity in older breast cancer patients. METHODS: Women diagnosed with non-metastatic breast cancer (n = 705) ages 60-98 were enrolled from August 2010-March 2020. Cognition was measured post-surgery, pre-systemic therapy using self-reported (FACT-Cog Perceived Cognitive Impairment [PCI]) and objective tests of attention, processing speed, and executive function (APE domain) and learning and memory [LM domain]. Linear regression tested associations of pre-treatment tumor features and cognition, adjusting for age, race, and study site. HER2 positivity and higher stage (II/III vs. 0/I) were a priori predictors of cognition; in secondary analyses we explored associations of other tumor features and cognitive impairment (i.e., PCI score < 54 or having 2 tests < 1.5 SD or 1 test < 2 SD from the mean APE or LM domain score). RESULTS: HER2 positivity and the hormone receptor negative/HER2 + molecular subtype were associated with lower adjusted mean self-reported cognition scores and higher impairment rates (p values < .05). Higher stage of disease was associated with lower objective performance in APE. Other tumor features were associated with cognition in unadjusted and adjusted models, including larger tumor size and lower PCI scores (p = 0.02). Tumor features were not related to LM. CONCLUSIONS: Pre-adjuvant therapy cognition was associated with HER2 positivity and higher stage of disease and other features of aggressive tumors. Additional research is needed to confirm these results and assess potential mechanisms and clinical management strategies.

Oral Chemotherapy Metric Performance in Quality Oncology Practice Initiative Practices: Updated Trends and Analysis.

BACKGROUND: Oral chemotherapy performance measures were first introduced into ASCO's Quality Oncology Practice Initiative (QOPI) in 2013. This study examined performance on these measures among QOPI-participating practices and evaluated whether it differed among practices based on meeting QOPI Certification Program standards. METHODS: A total of 192 QOPI-participating practices (certified, n=50 [26%]; not certified, n=142 [74%]) reported performance on oral chemotherapy measures in 2017 and 2018. Inclusion was limited to practices reporting on ≥3 charts for ≥1 oral chemotherapy measure. Performance was defined as the percentage of charts examined that adhered to the measure. Descriptive analyses were used to characterize performance within and across practices, and mixed-effects logistic regression models were conducted to compare performance based on certification status. RESULTS: Median performance across practices for the 9 oral chemotherapy measures examined ranged from 44% (education before the start of treatment addressing missed doses, toxicities, and clinical contact instructions [composite measure]) to 100% (documented dose, documented plan, and education about toxicities). Certified practices were more likely to provide education about clinic contact instructions than noncertified practices (odds ratio, 4.87; 95% CI, 1.00-24.0). Performance on all other measures was not significantly associated with certification status. CONCLUSIONS: There is wide variability in quality related to performance on oral chemotherapy measures across all QOPI-participating practices, and several areas were identified in which administration of oral chemotherapy could be improved. Our findings highlight the need for the development and implementation of appropriate standards that apply to oral chemotherapy and address the complexities that set it apart from parenteral treatment.

Associations between mental health and care experiences among older adults with cancer.

OBJECTIVE: We sought to understand whether people with cancer who received mental health services reported different care experiences than those who did not. METHODS: We used Surveillance, Epidemiology, and End Results (SEER)-Consumer Assessment of Health Providers and Systems (CAHPS) linked data to identify Medicare beneficiaries aged 66 and over diagnosed with solid tumor malignancies between 8/2006 and 12/2013. We identified mental health services using claims spanning 12 months before cancer diagnosis through up to 5 years afterward. Outcomes were care experience ratings (e.g., Overall Care) and composite measures (e.g., Doctor Communication). We estimated frequentist and Bayesian regression models adjusted for standard confounders, including sociodemographics, general and mental health status (MHS), and other characteristics. Models included interaction terms to understand whether mental healthcare changes self-reported experiences for individuals with adverse MHS. RESULTS: Approximately 22% (n = 4998 individuals with cancer) had a mental health disorder claim; 17% of these reported fair/poor MHS versus only 7% of those in the cancer-only cohort (without a mental health disorder claim). Before adjusting for mental healthcare utilization and case-mix, worse MHS was associated with worse care experiences (p < 0.001 for all six measures). After accounting for mental health disorder-related healthcare utilization and case mix, multivariable regression models showed no associations between MHS and worse care experiences. CONCLUSIONS: Care for mental health disorders mediates the association between MHS and perceived care experiences. The results suggest that mental health treatment may improve the self-reported experiences of care for older adults with cancer and adverse mental health issues.

Spiritual well-being, distress and quality of life in Hispanic women diagnosed with cancer undergoing treatment with chemotherapy.

OBJECTIVE: Previous studies have examined whether spiritual well-being is associated with cancer outcomes, but minority populations are under-represented. This study examines associations of baseline spiritual well-being and change in spiritual well-being with change in distress and quality of life, and explores potential factors associated with changes in spiritual well-being among Hispanic women undergoing chemotherapy. METHODS: Participants completed measures examining spiritual well-being, distress, and quality of life prior to beginning chemotherapy and at weeks 7 and 13. Participants' acculturation and sociodemographic data were collected prior to treatment. Mixed models were used to examine the association of baseline spiritual well-being and change in spiritual well-being during treatment with change in distress and quality of life, and to explore whether sociodemographic factors, acculturation and clinical variables were associated with change in spiritual well-being. RESULTS: A total of 242 participants provided data. Greater baseline spiritual well-being was associated with less concurrent distress and better quality of life (p < 0.001), as well as with greater emotional and functional well-being over time (p values < 0.01). Increases in spiritual well-being were associated with improved social well-being during treatment, whereas decreases in spiritual well-being were associated with worsened social well-being (p < 0.01). Married participants reported greater spiritual well-being at baseline relative to non-married participants (p < 0.001). CONCLUSIONS: Greater spiritual well-being is associated with less concurrent distress and better quality of life, as well as with greater emotional, functional, and social well-being over time among Hispanic women undergoing chemotherapy. Future work could include developing culturally targeted spiritual interventions to improve survivors' well-being.

Fatigue Perpetuating Factors as Mediators of Change in a Cognitive Behavioral Intervention for Targeted Therapy-Related Fatigue in Chronic Myeloid Leukemia: A Pilot Study.

BACKGROUND: Cognitive behavioral therapy for targeted-therapy related fatigue (CBT-TTF) has demonstrated preliminary efficacy in reducing fatigue in patients treated with tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia (CML). PURPOSE: The aim of the current analyses was to explore whether fatigue perpetuating factors (disturbed sleep/wake cycle, dysregulated activity patterns, maladaptive cognitions about fatigue and cancer, insufficient processing of cancer and treatment, inadequate social support and interactions, heightened fear of cancer progression) changed over time in patients receiving CBT-TTF, and whether the effect of CBT-TTF on fatigue was mediated by these factors. METHODS: Secondary data analyses were conducted from a pilot randomized controlled trial. Patients with CML treated with a TKI who reported moderate to severe fatigue were randomized 2:1 to CBT-TTF delivered via FaceTime for iPad or a waitlist control condition (WLC). Self-report measures of fatigue and fatigue perpetuating factors were obtained before randomization and post-intervention (i.e., approximately 18 weeks later). Mixed model and mediation analyses using bootstrap methods were used. RESULTS: A total of 36 participants (CBT-TTF n = 22, WLC n = 14) who had baseline and 18-week follow-up data and attended >5 sessions for CBT-TTF were included. Participants randomized to CBT-TTF reported improvements in activity (mental, physical, social, p's ≤ .023) and cognitions (helplessness, catastrophizing, focusing on symptoms, self-efficacy, p's ≤ .003) compared to WLC. Mental activity, social activity, self-efficacy, helplessness, and focusing on symptoms, as well as sleep and insufficient processing (avoidance) mediated the relationship between treatment group and fatigue. CONCLUSIONS: CBT-TTF appears to improve TKI-related fatigue in CML patients through changes in behavior (sleep, activity patterns) and cognitions about fatigue and cancer. A larger randomized controlled trial is warranted to confirm these findings.

Screening, evaluation, and management of cancer-related fatigue: Ready for implementation to practice?

Answer questions and earn CME/CNE Evidence regarding cancer-related fatigue (fatigue) has accumulated sufficiently such that recommendations for screening, evaluation, and/or management have been released recently by 4 leading cancer organizations. These evidence-based fatigue recommendations are available for clinicians, and some have patient versions; but barriers at the patient, clinician, and system levels hinder dissemination and implementation into practice. The underlying biologic mechanisms for this debilitating symptom have not been elucidated completely, hindering the development of mechanistically driven interventions. However, significant progress has been made toward methods for screening and comprehensively evaluating fatigue and other common symptoms using reliable and valid self-report measures. Limited data exist to support the use of any pharmacologic agent; however, several nonpharmacologic interventions have been shown to be effective in reducing fatigue in adults. Never before have evidence-based recommendations for fatigue management been disseminated by 4 premier cancer organizations (the National Comprehensive Cancer, the Oncology Nursing Society, the Canadian Partnership Against Cancer/Canadian Association of Psychosocial Oncology, and the American Society of Clinical Oncology). Clinicians may ask: Are we ready for implementation into practice? The reply: A variety of approaches to screening, evaluation, and management are ready for implementation. To reduce fatigue severity and distress and its impact on functioning, intensified collaborations and close partnerships between clinicians and researchers are needed, with an emphasis on system-wide efforts to disseminate and implement these evidence-based recommendations.

Correlates of fatigue severity in patients with chronic myeloid leukemia treated with targeted therapy.

PURPOSE: Tyrosine kinase inhibitors (TKIs) substantially improve survival for patients with chronic myeloid leukemia (CML), but fatigue associated with TKIs can negatively impact patients' quality of life and adherence. This study sought to identify correlates of fatigue (e.g., sociodemographic characteristics, clinical characteristics, health behaviors) among patients with CML taking TKIs who reported moderate to severe fatigue. METHODS: Adults with CML experiencing at least moderate fatigue were recruited for a pilot trial of a cognitive behavioral intervention to improve fatigue. Data collected pre-intervention were used to explore concurrent correlates of fatigue in univariate and multivariable models. RESULTS: Participants (N = 44, 48% female) were M = 55.6 years old (SD = 12.6) and had been diagnosed with CML M = 5.2 years prior (SD = 5.3). Participants had been taking their current TKI for M = 2.5 years (SD = 2.7). Most participants (64%) had previously been treated with ≥ 1 other TKI. More than three-quarters of participants (77%) reported severe fatigue. In univariate models, worse fatigue was associated with higher BMI (r = -0.36, p = 0.018), prior treatment with other TKI(s) (r = - 0.34, p = 0.024), worse sleep disturbance (r = - 0.51, p < 0.001), and less physical activity (r = 0.31, p = 0.043). In a multivariable model, significant univariate correlates accounted for 39% of the variance in fatigue. Worse fatigue remained significantly correlated with higher BMI (ß = - 0.33, p = 0.009) and more disturbed sleep (ß = - 0.45, p < 0.001). CONCLUSION: Results may inform future research aiming to identify fatigued patients with CML at risk for experiencing more severe fatigue during TKI therapy. Identifying predictors of fatigue severity could aid clinicians in identifying which patients will benefit from referrals to supportive therapy. TRIAL REGISTRATION: NCT02592447, October 30, 2015.

Systemic inflammation and symptomatology in patients with prostate cancer treated with androgen deprivation therapy: Preliminary findings.

BACKGROUND: Increases in fatigue, depressive symptomatology, and cognitive impairment are common after the initiation of androgen deprivation therapy (ADT) for prostate cancer. To date, no studies have examined the potential role of inflammation in the development of these symptoms in ADT recipients. The goal of the current study was to examine circulating markers of inflammation as potential mediators of change in fatigue, depressive symptomatology, and cognitive impairment related to the receipt of ADT. METHODS: Patients treated with ADT for prostate cancer (ADT+; n = 47) were assessed around the time of the initiation of ADT and 6 and 12 months later. An age- and education-matched group of men without a history of cancer (CA-; n = 82) was assessed at comparable time points. Fatigue, depressive symptomatology, and cognitive impairment were assessed with the Fatigue Symptom Inventory, the Center for Epidemiological Studies Depression Scale, and a battery of neuropsychological tests, respectively. Circulating markers of inflammation included interleukin 1 receptor antagonist (IL-1RA), interleukin 6 (IL-6), soluble tumor necrosis factor receptor II (sTNF-RII), and C-reactive protein (CRP). RESULTS: Fatigue, depressive symptomatology, and serum IL-6 increased significantly over time in the ADT+ group versus the CA- group; rates of cognitive impairment also changed significantly between the groups. No significant changes in IL-1RA, sTNF-RII, or CRP over time were detected. Treatment-related increases in IL-6 were associated with worsening fatigue but not depressive symptomatology or cognitive impairment. CONCLUSIONS: Results of this preliminary study suggest that increases in circulating IL-6, perhaps due to testosterone inhibition, may play a role in fatigue secondary to receipt of ADT. Additional research is needed to determine whether interventions to reduce circulating inflammation improve fatigue in this population.

Contribution of Sleep Disruption and Sedentary Behavior to Fatigue in Survivors of Allogeneic Hematopoietic Cell Transplant.

BACKGROUND: Fatigue is a prominent quality of life concern among recipients of hematopoietic cell transplantation (HCT). PURPOSE: The present study investigated whether objectively measured sleep efficiency and sedentary behavior are related to greater reports of fatigue. METHODS: Eighty-two allogeneic HCT recipients who were 1-5 years post-transplant and returning for a follow-up visit participated (age M = 56, 52% female, 56% leukemia). They wore an actigraph assessing sleep efficiency and sedentary behavior for one week and completed an electronic log assessing fatigue each evening during the same period. RESULTS: Twenty-six percent of patients reported clinically meaningful fatigue. On average, fatigue was mild (M = 2.5 on 0-10 scale, SD = 2.0), sleep was disturbed (sleep efficiency M = 78.9%, SD = 8.9), and patients spent the majority of time in sedentary (M = 55.4%, SD = 10.2) or light (M = 35.9%, SD = 8.6) activity. Multilevel model analysis of between-person differences indicated that patients who experienced less efficient sleep the previous evening provided greater evening reports of average fatigue, b = -0.06, 95% CI (-0.11, -0.01). Similarly, within-person analyses indicated that when patients experienced less efficient sleep the previous evening or were more sedentary as compared to their average, they provided greater evening reports of average fatigue, b = -0.02, 95% CI (-0.05, -0.004); b = 4.46, 95% CI (1.95, 6.97), respectively. CONCLUSIONS: Findings demonstrate that poor sleep and daily sedentary behavior are related to evening reports of fatigue and should be considered modifiable targets for intervention.

An examination of the relationship of patient modifiable and non-modifiable characteristics with fear of cancer recurrence among colorectal cancer survivors.

PURPOSE: Fear of cancer recurrence (FCR) is one of the most common and distressing issues affecting cancer survivors. This study examined (1) the association between modifiable cognitive, behavioral, and social characteristics and FCR, (2) the association between non-modifiable characteristics and FCR, and (3) the relative contributions of modifiable and non-modifiable characteristics to FCR. METHODS: Participants (n = 120) had been diagnosed with colorectal cancer and completed cancer treatment in the past 6 to 36 months. Participants completed self-report measures of modifiable cognitive (e.g., beliefs about worry), behavioral (e.g., health-related reassurance seeking), and social (e.g., social constraints) characteristics. Non-modifiable characteristics (e.g., age, disease severity) were assessed via self-report and medical record review. FINDINGS: Modifiable (i.e., perceived risk, self-efficacy, positive beliefs about worry, negative beliefs about worry, intolerance of uncertainty, rumination, reassurance seeking, health-related reassurance seeking, social constraints) and non-modifiable (i.e., age, gender, disease severity, neuroticism, conscientiousness) characteristics were associated with FCR (p's < .05). Hierarchical linear regression analyses demonstrated that modifiable characteristics accounted for an additional 15% of the variance (p < .001) beyond that accounted for by non-modifiable characteristics (R2 = .45, p < .001), with perceived risk (B = .35) and health-related reassurance seeking (B = .22) emerging as significant predictors of FCR (p's < .05). IMPLICATIONS: Results identify non-modifiable characteristics that may serve as risk factors for greater FCR and identify specific modifiable characteristics (i.e., perceived risk, health-related reassurance seeking) to be targeted by interventions to reduce FCR among cancer survivors.

Preventing smoking relapse in patients with cancer: A randomized controlled trial.

BACKGROUND: Abstaining from smoking after a cancer diagnosis is critical to mitigating the risk of multiple adverse health outcomes. Although many patients with cancer attempt to quit smoking, the majority relapse. The current randomized controlled trial evaluated the efficacy of adapting an evidence-based smoking relapse prevention (SRP) intervention for patients with cancer. METHODS: The trial enrolled 412 patients newly diagnosed with cancer who had recently quit smoking. Participants were randomized to usual care (UC) or SRP. Participants in the UC group received the institution's standard of care for treating tobacco use. Participants in the SRP group in addition received a targeted educational DVD plus a validated self-help intervention for preventing smoking relapse. The primary outcome was smoking abstinence at 2 months, 6 months, and 12 months. RESULTS: Abstinence rates for participants in the SRP and UC groups were 75% versus 71% at 2 months and 69% versus 64% at 6 months (Ps > .20). At 12 months, abstinence rates among survivors were 68% for those in the SRP group and 63% for those in the UC group (P = .38). Post hoc analyses revealed that across 2 months and 6 months, patients who were married/partnered were more likely to be abstinent after SRP than UC (P = .03). CONCLUSIONS: A smoking relapse prevention intervention did not reduce relapse rates overall, but did appear to have benefited those participants who had the social support of a partner. Future work is needed to extend this effect to the larger population of patients.

Internet-assisted cognitive behavioral intervention for targeted therapy-related fatigue in chronic myeloid leukemia: Results from a pilot randomized trial.

BACKGROUND: Fatigue is a common and disabling side effect of targeted therapies such as tyrosine kinase inhibitors (TKIs) used to treat chronic myeloid leukemia (CML). The goal of the current study was to conduct a pilot randomized trial of the first cognitive behavioral intervention developed for fatigue due to targeted therapy. METHODS: Patients with CML treated with a TKI who were reporting moderate to severe fatigue were recruited and randomized 2:1 to cognitive behavioral therapy for targeted therapy-related fatigue (CBT-TTF) delivered via FaceTime for the iPad or to a waitlist control (WLC) group. The outcomes were acceptability, feasibility, and preliminary efficacy for fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue; primary outcome) and quality of life (Functional Assessment of Cancer Therapy-General; secondary outcome). Participants were assessed before randomization and after treatment (ie, approximately 18 weeks later). RESULTS: A total of 44 patients (mean age, 55 years; 48% female) were assigned to CBT-TTF (n = 29) or WLC (n = 15). The study participation rate was 59%. Among the patients assigned to CBT-TTF, 79% completed the intervention. Intent-to-treat analyses indicated that patients assigned to CBT-TTF demonstrated greater improvements in fatigue (d = 1.06; P < .001) and overall quality of life (d = 1.15; P = .005) than those assigned to WLC. More patients randomized to CBT-TTF than WLC demonstrated clinically significant improvements in fatigue (85% vs 29%) and quality of life (88% vs 54%; P values ≤ .016). CONCLUSIONS: CBT-TTF displays preliminary efficacy in improving fatigue and quality of life among fatigued patients with CML treated with TKIs. The findings suggest that a larger randomized study is warranted.