Mindful Night-to-Day: A Pilot Feasibility Trial of a Mindfulness-Based Insomnia and Symptom Management Intervention for Patients with Hematologic Cancer.

OBJECTIVES: Patients with hematologic cancer experience severe symptoms (i.e. insomnia, fatigue, pain, distress). Few interventions addressing insomnia and other symptoms exist for this population. Mindfulness-Based Therapy for Insomnia (MBTI) may be appropriate but has only been tested in healthy outpatients. This study aimed to develop and test an adapted MBTI protocol for hematologic cancer patients. METHODS: Patient (n = 3) and clinician (n = 1) focus groups, and user-testing (N = 5) informed adaptation of Mindful Night-to-Day (MBTI+). A single-arm pilot trial (N = 32) evaluated feasibility (accrual, attrition, adherence), acceptability (intervention satisfaction), and changes to insomnia symptom severity (Insomnia Severity Index; primary outcome) and secondary outcomes (fatigue, pain, distress, pre-sleep arousal, mindfulness, symptom management self-efficacy) at baseline, post-intervention, and 1-month post-intervention. Descriptive statistics and paired sample t-tests were conducted. RESULTS: Qualitative feedback informed MBTI+ content, format, and delivery. Mindfulness was used to increase symptom awareness (sleepiness vs. fatigue). Meditations and behavioral skills were applied to inpatient treatment. MBTI+ met feasibility (N = 32/12 months; 8.1% attrition; 83.8% adherence) and acceptability (M = 3.52/4.00) benchmarks. Insomnia symptom severity decreased (d = 1.20) from baseline to post-intervention, as did most secondary outcomes. CONCLUSIONS: MBTI+ was feasible, acceptable, and showed promise for benefits throughout inpatient and outpatient treatment. Findings warrant further evaluation in a randomized trial.

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.

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.

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.

Quality of life in caregivers of patients receiving chimeric antigen receptor T-cell therapy.

OBJECTIVE: Informal family caregivers provide critical support for patients receiving chimeric antigen receptor (CAR) T-cell therapy. However, caregivers' experiences are largely unstudied. This study examined quality of life (QOL; physical functioning, pain, fatigue, anxiety, and depression), caregiving burden, and treatment-related distress in caregivers in the first 6 months after CAR T-cell therapy, when caregivers were expected to be most involved in providing care. Relationships between patients' clinical course and caregiver outcomes were also explored. METHODS: Caregivers completed measures examining QOL and burden before patients' CAR T-cell therapy and at days 90 and 180. Treatment-related distress was assessed at days 90 and 180. Patients' clinical variables were extracted from medical charts. Change in outcomes was assessed using means and 99% confidence intervals. Association of change in outcomes with patient clinical variables was assessed with backward elimination analysis. RESULTS: A total of 99 caregivers (mean age 59, 73% female) provided data. Regarding QOL, pain was significantly higher than population norms at baseline but improved by day 180 (p < .01). Conversely, anxiety worsened over time (p < .01). Caregiver burden and treatment-related distress did not change over time. Worsening caregiver depression by day 180 was associated with lower patient baseline performance status (p < .01). Worse caregiver treatment-related distress at day 180 was associated with lower performance status, intensive care unit admission, and lack of disease response at day 90 (ps < 0.01). CONCLUSIONS: Some CAR T-cell therapy caregivers experience pain, anxiety, and burden, which may be associated patients' health status. Further research is warranted regarding the experience of CAR T-cell therapy caregivers.

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.

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.

Effect of Sustained Smoking Cessation Counseling and Provision of Medication vs Shorter-term Counseling and Medication Advice on Smoking Abstinence in Patients Recently Diagnosed With Cancer: A Randomized Clinical Trial.

Importance: Persistent smoking may cause adverse outcomes among patients with cancer. Many cancer centers have not fully implemented evidence-based tobacco treatment into routine care. Objective: To determine the effectiveness of sustained telephone counseling and medication (intensive treatment) compared with shorter-term telephone counseling and medication advice (standard treatment) to assist patients recently diagnosed with cancer to quit smoking. Design, Setting, and Participants: This unblinded randomized clinical trial was conducted at Massachusetts General Hospital/Dana-Farber/Harvard Cancer Center and Memorial Sloan Kettering Cancer Center. Adults who had smoked 1 cigarette or more within 30 days, spoke English or Spanish, and had recently diagnosed breast, gastrointestinal, genitourinary, gynecological, head and neck, lung, lymphoma, or melanoma cancers were eligible. Enrollment occurred between November 2013 and July 2017; assessments were completed by the end of February 2018. Interventions: Participants randomized to the intensive treatment (n = 153) and the standard treatment (n = 150) received 4 weekly telephone counseling sessions and medication advice. The intensive treatment group also received 4 biweekly and 3 monthly telephone counseling sessions and choice of Food and Drug Administration-approved cessation medication (nicotine replacement therapy, bupropion, or varenicline). Main Outcome and Measures: The primary outcome was biochemically confirmed 7-day point prevalence tobacco abstinence at 6-month follow-up. Secondary outcomes were treatment utilization rates. Results: Among 303 patients who were randomized (mean age, 58.3 years; 170 women [56.1%]), 221 (78.1%) completed the trial. Six-month biochemically confirmed quit rates were 34.5% (n = 51 in the intensive treatment group) vs 21.5% (n = 29 in the standard treatment group) (difference, 13.0% [95% CI, 3.0%-23.3%]; odds ratio, 1.92 [95% CI, 1.13-3.27]; P < .02). The median number of counseling sessions completed was 8 (interquartile range, 4-11) in the intensive treatment group. A total of 97 intensive treatment participants (77.0%) vs 68 standard treatment participants (59.1%) reported cessation medication use (difference, 17.9% [95% CI, 6.3%-29.5%]; odds ratio, 2.31 [95% CI, 1.32-4.04]; P = .003). The most common adverse events in the intensive treatment and standard treatment groups, respectively, were nausea (n = 13 and n = 6), rash (n = 4 and n = 1), hiccups (n = 4 and n = 1), mouth irritation (n = 4 and n = 0), difficulty sleeping (n = 3 and n = 2), and vivid dreams (n = 3 and n = 2). Conclusions and Relevance: Among smokers recently diagnosed with cancer in 2 National Cancer Institute-designated Comprehensive Cancer Centers, sustained counseling and provision of free cessation medication compared with 4-week counseling and medication advice resulted in higher 6-month biochemically confirmed quit rates. However, the generalizability of the study findings is uncertain and requires further research. Trial Registration: ClinicalTrials.gov Identifier: NCT01871506.

Loneliness as a mediator of the relationship of social cognitive variables with depressive symptoms and quality of life in lung cancer patients beginning treatment.

OBJECTIVE: Loneliness, or the discrepancy between perceived and desired level of social connectedness, is an understudied but important psychosocial factor in cancer patients. The current study investigated the relationship between loneliness, depressive symptoms, quality of life, and social cognitive variables (eg, stigma, social constraint, and cancer-related negative social expectations), and explored loneliness as a mediator of the relationship between social cognitive variables and depressive symptoms and quality of life in lung cancer patients beginning treatment. METHODS: Patients within 3 months of beginning treatment for lung cancer completed measures of loneliness, depressive symptoms, quality of life, and social cognitive variables. Correlational, chi-square, and hierarchical regression analyses evaluated relationships among variables. Bias-corrected bootstrapping methods estimated the indirect effect and 95% confidence interval for mediation models. RESULTS: Participants (n = 105, M = 65.5 years, 55% female) endorsed low to moderate levels of loneliness. Greater loneliness was associated with greater depressive symptoms and worse quality of life (P's < .001), and loneliness explained unique variance in depressive symptoms (F = 10.18, P < .001, ΔR2  = .06, Total R2  = .35) and quality of life (F = 19.55, P < .001, ΔR2  = .05, Total R2  = .52) after controlling for significant covariates. Greater stigma, social constraint, and cancer-related negative social expectations were associated with greater loneliness and depressive symptoms and worse quality of life (P's < .001). Loneliness partially mediated the relationship of social cognitive variables with depressive symptoms and quality of life. CONCLUSIONS: Beyond its direct impact on clinically relevant outcomes, the experience of loneliness may be a mechanism by which social cognitive factors influence depressive symptoms and quality of life in lung cancer patients.