Cognition in patients treated with targeted therapy for chronic myeloid leukemia: a controlled comparison.

This controlled comparison study evaluated objective and subjective cognitive function and their relationships with patient-reported symptoms (depression, fatigue, insomnia) in patients receiving tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia (CML) and non-cancer controls. Patients with CML in chronic phase treated with the same oral TKI for ≥6 months (n = 90) and non-cancer controls (n = 87) completed a neurocognitive battery and self-report measures. Patients demonstrated worse overall neuropsychological performance (p = .05) and verbal memory (p = .02) compared to controls. Patients were not more likely to meet criteria for impaired cognitive performance compared to controls (ps>.26). Patients reported worse subjective global and domain-specific cognitive complaints and less satisfaction with cognitive function compared to controls (ps < .05). Patients also reported greater fatigue and insomnia symptoms (ps < .001). In both groups, greater fatigue, insomnia, and depressive symptoms were associated with worse subjective cognition (ps < .01). Longitudinal studies are needed to examine changes in cognitive function in patients before and during TKI treatment.

Cumulative burden of symptomatology in patients with gynecologic malignancies undergoing chemotherapy.

OBJECTIVE: Patients with gynecologic malignancies commonly experience distressing symptoms during chemotherapy. This study sought to evaluate whether symptoms accumulated over the course of several chemotherapy cycles, which could provide essential information for planning supportive interventions. METHOD: Patients with gynecologic malignancies completed questionnaires about fatigue, depressive symptoms, sleep, and physical activity 1 week before and after chemotherapy cycles 1, 3, and 6. Multilevel models examined the effects of time (pre- and postchemotherapy), treatment cycle (1, 3, 6), and their interaction on symptoms. Logistic regression models examined the effects of time, treatment cycle, and their interaction on the proportion of participants exceeding thresholds for clinically meaningful symptomatology. RESULTS: Most participants (N = 140; Mage = 60.8 years, SD = 10.4) had ovarian cancer (49%) and Stage III disease (55%). Participants reported worse fatigue, depressive symptoms, sleep disturbance, and sleep efficiency from pre- to posttreatment at each cycle (ps < .001). With each successive cycle, participants reported worse pretreatment fatigue (p < .001) and depressive symptoms (p < .01) but better sleep efficiency (p = .02). Fatigue increases attenuated across cycles (p = .04). There were no changes in physical activity. Across time points, at least half of participants met clinical thresholds for fatigue, sleep disturbance, and low sleep efficiency and were minimally physically active. Postchemotherapy cycle 6, 23% of participants reported clinically meaningful depressive symptoms. CONCLUSIONS: Patients with gynecologic malignancies have high rates of clinically meaningful symptomatology during chemotherapy. Patients may experience a cumulative burden of symptomatology as treatment progresses, which could have therapeutic implications. Early implementation of supportive interventions should be considered to prevent or mitigate cumulative treatment burden. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Change in Patients' Perceived Cognition Following Chimeric Antigen Receptor T-Cell Therapy for Lymphoma.

Chimeric antigen receptor (CAR) T-cell therapy can lead to durable responses in patients with relapsed/refractory hematologic malignancies. Immune effector cell-associated neurotoxicity syndrome (ICANS) and cytokine release syndrome (CRS) are common and may place patients at risk for longer-term cognitive impairment. This study examined changes in cognition in the first year after CD19-directed CAR T-cell therapy for lymphoma, as well as CAR T-cell therapy-specific risk-factors (e.g., ICANS, CRS) and nonspecific risk factors (e.g., baseline quality of life, frailty) for worsening cognition. Patients' perceived cognition was assessed at baseline and at days 90 and 360. Clinical variables were abstracted from medical records. Piecewise mixed models were used to examine acute change (i.e., within 90 days) and longer-term change (i.e., from 90 days to 360 days) in cognition, as well as to explore risk factors for worsening cognition. Among 118 participants (mean age 61, 59% male), mean levels of perceived cognition did not change from baseline to day 90 (P> .05) but worsened from day 90 to day 360 in global cognition and in the domains of memory, language, organization, and divided attention (P< .05). Although statistically significant, changes were small (d values 0.15-0.28). Greater baseline fatigue, anxiety, and depression were associated with worse global cognition at day 90 (P< .01). Patients with more severe ICANS post-CART reported worse global cognition at day 360 (P< .05), although there were no differences in perceived cognition by severity of CRS (P> .05). Other putative risk factors were not associated with acute or longer-term changes in perceived cognition (P> .05). CAR T-cell therapy recipients reported delayed deterioration in several cognitive domains, although changes were small. These findings may be useful when educating future patients on what to expect when receiving CAR T-cell therapy.

Pilot randomized controlled trial of eHealth cognitive-behavioral therapy for insomnia among Spanish-speaking breast cancer survivors.

Cognitive-Behavioral Therapy for Insomnia (CBT-I) is the gold-standard treatment for insomnia, which is common among breast cancer survivors (BCS). This pilot randomized controlled trial tested the first CBT-I intervention for Spanish-speaking BCS delivered using eHealth. Participants (N = 30) were Spanish-speaking BCS with insomnia symptoms recruited in Puerto Rico and randomized to a 6-week eHealth CBT-I group intervention or a waitlist control. Primary outcomes were acceptability (recruitment, treatment satisfaction) and feasibility (retention, attendance). Secondary outcomes were group differences in sleep outcomes post-treatment (i.e., insomnia symptoms, sleep disturbance, sleep efficiency). Recruitment (95%) and retention (97%) were excellent. All CBT-I participants (100%) attended ≥ 3 of 6 sessions. Satisfaction with CBT-I was acceptable. Post-intervention, there were medium to large group differences for average insomnia symptoms (d = 1.02), sleep disturbance (d = 1.25), and sleep efficiency (d = 0.77) favoring CBT-I. There were small/medium to medium/large group differences for the proportion of participants with clinically significant insomnia symptoms (d = 0.52), sleep disturbance (d = 0.67), and low sleep efficiency (d = 0.33) favoring CBT-I. Spanish-language eHealth CBT-I for BCS was acceptable and feasible and showed preliminary efficacy.ClinicalTrials.gov TRN: NCT04101526 (Posted September 24, 2019).

Change in Neurocognitive Performance Among Patients with Non-Hodgkin Lymphoma in the First Year after Chimeric Antigen Receptor T Cell Therapy.

The success of chimeric antigen receptor (CAR) T cell therapy in treating patients with relapsed/refractory hematologic malignancies is leading to a growing number of survivors treated with this regimen. To our knowledge, no previous studies have examined neurocognitive performance in adult CAR T cell therapy recipients, despite high rates of neurotoxicity and cytokine release syndrome (CRS) in the acute treatment period. This study examined changes in neurocognitive performance in the first year after CAR T cell therapy for non-Hodgkin lymphoma (NHL). Putative risk factors for worsening neurocognitive performance (eg, neurotoxicity, CRS) were explored as well. Neurocognition was assessed before initiation of CAR T cell therapy and at 30, 90, and 360 days post-treatment. Clinical variables were abstracted from medical records. Mixed models were used to examine change in total neurocognitive performance (TNP) and cognitive domains (ie, attention, executive function, verbal ability, immediate and delayed memory, and visuospatial abilities). Among 117 participants (mean age, 61 years; 62% male), TNP and executive function declined slightly on average from baseline to day 90 and then improved from day 90 to day 360 (P < .04). Small but significant linear declines in visuospatial ability on average were also observed over time (P = .03). Patients who had 4 or more lines of previous therapy and those with worse neurotoxicity (but not CRS) demonstrated worse TNP. CAR T cell therapy recipients reported transient or persistent deterioration in several cognitive domains, although changes were slight. These findings may be useful when educating future patients on what to expect when receiving CAR T cell therapy.

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.

Meta-Analysis of Quality of Life in Cancer Patients Treated With Immune Checkpoint Inhibitors.

BACKGROUND: Trials of immune checkpoint inhibitors (ICIs) have published patient-reported quality of life (QOL), but the size and heterogeneity of this literature can make patient education difficult. This meta-analysis aimed to describe change in QOL and symptomatology in patients receiving ICIs for cancer. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, databases were searched through November 2019 for articles or abstracts of prospective, original studies reporting longitudinal QOL in adult cancer patients treated with ICIs. The prespecified primary outcomes were change in global QOL among patients treated with ICIs and difference in change since baseline in global QOL between patients treated with ICI vs non-ICI active treatment. Secondary outcomes included physical functioning and symptomatology. All statistical tests were 2-sided. RESULTS: Of 20 323 publications, 26 met inclusion criteria. Global QOL did not change over time in patients treated with ICIs (k = 26, n = 6974; P = .19). Larger improvements in global QOL was observed in patients receiving ICI vs non-ICI regimens (k = 16, ICI: n = 3588; non-ICI: n = 2948; P < .001). Physical functioning did not change in patients treated with ICIs (k = 14, n = 3169; P = .47); there were no differences in mean change between ICI vs non-ICI regimens (k = 11, n = 4630; P = .94). Regarding symptoms, appetite loss, insomnia, and pain severity decreased, but dyspnea severity increased in patients treated with ICIs (k = 14, n = 3243-3499; P < .001). Insomnia severity was higher in patients treated with ICIs than non-ICI regimens (k = 11, n = 4791; P < .001). CONCLUSIONS: This study is among the first to quantitatively summarize QOL in patients treated with ICIs. Findings suggest ICI recipients report no change in global QOL and higher QOL than patients treated with non-ICI regimens.

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.

A 2-year prospective analysis of insomnia as a mediator of the relationship between androgen deprivation therapy and perceived cognitive function in men with prostate cancer.

BACKGROUND: Androgen deprivation therapy (ADT) may affect cognitive function in men with prostate cancer (PCa). This study examined whether insomnia symptoms mediate the relationship between ADT and perceived cognitive function and whether depressive symptoms, fatigue severity, and physical activity moderate the strength of this relationship. METHODS: This was a prospective study of ADT recipients (n = 83) who were matched with control patients with PCa who were not on ADT (n = 92) and with controls with no history of cancer (n = 112) over a 2-year follow-up period. Perceived cognitive function and satisfaction were assessed with the Everyday Cognition Scale. Insomnia was assessed with the Insomnia Severity Index. Multilevel mediation analyses were conducted to estimate the indirect effect of ADT on perceived cognitive function through insomnia symptoms. Exploratory moderated mediation analyses assessed whether the indirect effect of ADT on perceived cognitive function through insomnia symptoms was dependent on levels of fatigue, depression, or physical activity. RESULTS: Insomnia symptoms significantly mediated the relationship between receipt of ADT and perceived cognitive function (P < .001) and satisfaction with cognition (P < .001) after controlling for comorbidities. Men with greater fatigue had a more pronounced association of ADT with insomnia severity. Men with greater depressive symptoms had a stronger association between insomnia severity and worse perceived cognitive function. Physical activity was not a significant moderator of the relationship between ADT and perceived cognitive function. CONCLUSIONS: Insomnia influenced the relationship between ADT and perceived cognitive abilities. Interventions to address insomnia, fatigue, and depression may improve perceived cognitive function.

Prevalence, risk factors, and trajectories of sleep disturbance in a cohort of African-American breast cancer survivors.

PURPOSE: Sleep disturbance may be an overlooked modifiable risk factor for health disparities among African-American breast cancer survivors (AABCS). This study aimed to identify the prevalence of and risk factors for sleep disturbance in a cohort of AABCS. METHODS: The study was conducted among participants in the Women's Circle of Health Follow-up Study, a longitudinal study of breast cancer in 10 counties in New Jersey. Cases were identified shortly after diagnosis by the New Jersey State Cancer Registry. Self-reported sleep disturbance (Pittsburgh Sleep Quality Index) and other factors (e.g., socioeconomic status, menopausal status) were assessed at pre-diagnosis (n = 637), 10 months post-diagnosis (n = 261), and 24 months post-diagnosis (n = 632). Clinical data were obtained via medical record abstraction, and height and weight were measured by study staff. RESULTS: Most AABCS (57%) reported clinically significant sleep disturbance before diagnosis, and this rate remained largely unchanged at 10 months (53%) and 24 months post-diagnosis (61%). Average sleep disturbance scores indicated clinically significant disturbance at all three assessments (M range = 6.67-7.57). Most reported sleeping fewer than the recommended 7 hours per night at each assessment (range 57-65%). Risk factors for sleep disturbance were identified at each assessment, including pre-diagnosis (less education), 10 months post-diagnosis (lack of insurance, treatment with chemotherapy), and 24 months post-diagnosis (younger age, less education, lower income, obesity, and lymphedema). Treatment with endocrine therapy was a protective factor at 10 months post-diagnosis. CONCLUSION: Most AABCS report clinically significant sleep disturbance from before diagnosis through 24 months post-diagnosis. These rates appear indicate AABCS experience significant sleep-related disparities.

Use of a Cancer Registry to Evaluate Patient-Reported Outcomes of Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) are increasingly used for advanced lung cancer, but few studies have reported on patient-reported outcomes (PROs) outside the context of a clinical trial. The goal of the current study was to assess PROs in participants of a lung cancer registry who had been treated with an ICI. Patients participating in the GO2 Foundation's Lung Cancer Registry who reported receiving atezolizumab, durvalumab, nivolumab, or pembrolizumab were invited to participate in a survey about their experiences during treatment. Quality of life was evaluated using the Functional Assessment of Cancer Therapy-General (FACT-G). Common symptomatic adverse events were evaluated using an item bank generated for ICIs. Internationally, 226 patients (mean age 61, 75% female) participated. Patients reported worse quality of life at the time of assessment than U.S. population and cancer normative samples. The most common moderate to severe adverse events during ICI treatment were fatigue (41%), aching joints (27%), and aching muscles (20%). Due to toxicity, 25% reported a treatment delay, 11% an emergency room visit, and 9% a hospitalization. This study is among the first to our knowledge to report on PROs of ICIs outside the context of a clinical trial. Results suggest higher rates of adverse events than previously reported in clinical trials.

Cognitive performance of breast cancer survivors in daily life: Role of fatigue and depressed mood.

OBJECTIVE: Cancer and its treatment are associated with long-term cognitive deficits. However, most studies of cancer patients have used traditional, office-based cognitive evaluations instead of assessing patients in their daily lives. Recent research in cognitive aging suggests that variability in performance may be a sensitive indicator of cognitive decline. Using ecological momentary assessment (EMA), we examined cognitive variability among breast cancer survivors and evaluated whether ratings of fatigue and depressed mood were associated with cognition. METHODS: Participants were 47 women (M age = 53.3 years) who completed treatment for early stage breast cancer 6 to 36 months previously. Smartphones were preloaded with cognitive tests measuring processing speed, executive functioning, and memory, as well as rating scales for fatigue and depressed mood. Participants were prompted five times per day over a 14-day period to complete EMA cognitive tasks and fatigue and depressed mood ratings. RESULTS: Cognitive variability was observed across all three EMA cognitive tasks. Processing speed responses were slower at times that women rated themselves as more fatigued than their average (P < .001). Ratings of depressed mood were not associated with cognition. CONCLUSIONS: This study is the first to report cognitive variability in the daily lives of women treated for breast cancer. Performance was worse on a measure of processing speed at times when a woman rated her fatigue as greater than her own average. The ability to identify moments when cognition is most vulnerable may allow for personalized interventions to be applied at times when they are most needed.

Nutraceutical intervention improves older adults' cognitive functioning.

Interventions to improve the cognitive health of older adults are of critical importance. In the current study, we conducted a double-blind, placebo-controlled clinical trial using a pill-based nutraceutical (NT-020) that contained a proprietary formulation of blueberry, carnosine, green tea, vitamin D3, and Biovin to evaluate the impact on changes in multiple domains of cognitive functioning. One hundred and five cognitively intact adults aged 65-85 years of age (M=73.6 years) were randomized to receive NT-020 (n=52) or a placebo (n=53). Participants were tested with a battery of cognitive performance tests that were classified into six broad domains--episodic memory, processing speed, verbal ability, working memory, executive functioning, and complex speed at baseline and 2 months later. The results indicated that persons taking NT-020 improved significantly on two measures of processing speed across the 2-month test period in contrast to persons on the placebo whose performance did not change. None of the other cognitive ability measures were related to intervention group. The results also indicated that the NT-020 was well tolerated by older adults, and the presence of adverse events or symptoms did not differ between the NT-020 and placebo groups. Overall, the results of the current study were promising and suggest the potential for interventions like these to improve the cognitive health of older adults.