Biological and psychological predictors of cognitive function in breast cancer patients before surgery.

PURPOSE: Research suggests that cancer-related cognitive impairment (CRCI) can occur before breast cancer (BC) treatment. The limited extant evidence suggests the underlying mechanisms could be stress-related. Potential psychological and biological predictors of CRCI prior to any BC treatment were examined. METHODS: 112 treatment-naïve women with BC and 67 healthy controls (HC) completed a neuropsychological test battery to assess cognitive impairment and a self-report battery to assess cognitive complaints, cancer-related stress, depressive and anxiety symptoms. Morning and evening cortisol and α-amylase were collected from saliva. Multilinear regressions were conducted. RESULTS: Treatment-naïve BC patients were more frequently impaired in verbal memory and processing speed and reported more cognitive complaints (all p < .001) than HC. BC patients and HC did not differ in overall cognitive impairment (p = .21). Steeper α-amylase, lower cancer-related stress and younger age was associated with better overall cognitive function in treatment-naïve BC patients. Higher depressive symptoms predicted higher levels of cognitive complaints in BC patients. CONCLUSION: Overall, these findings suggest that stress plays a role in CRCI. This study is the first to associate α-amylase with cognitive function in cancer patients, informing future research. The findings on impairment in processing speed and verbal memory among treatment-naïve BC highlight the need to screen for such impairments among BC patients and indicate that future studies on CRCI should include baseline assessments prior to BC treatment. If replicated, these findings could inform the development and testing of appropriate interventions to decrease CRCI among cancer patients. CLINICAL TRIALS REGISTRATION NUMBER: NCT04418856, date of registration: 06.05.2020.

Psychological and behavioral symptoms in patients with melanoma: A systematic review and meta-analysis.

OBJECTIVE: Improved survival rates have made it increasingly important for clinicians to focus on cancer survivorship issues affecting the quality of life of melanoma patients. To provide a comprehensive overview of the disease and treatment-related issues affecting such patients, we conducted a systematic review and meta-analysis of the literature to estimate the prevalence of symptoms of depression, anxiety, fatigue, sleep disturbance, and cognitive problems among melanoma patients, both uveal and cutaneous, before, during and after treatment. METHODS: The review was preregistered with PROSPERO (#CRD42020189847) and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search of the literature published up until June 2022 was undertaken using PubMed, PsycInfo, the Cochrane Library, and CINAHL. Two independent reviewers screened 1418 records and quality-rated included studies. The reported prevalence rates of symptoms were pooled using a random-effects model. RESULTS: Sixty-six studies including a total of 12,400 melanoma patients published between 1992 and 2022 were included. Pooled prevalence rates ranged from 6% to 16% for depression and 7%-30% for anxiety across diagnoses (uveal and cutaneous melanoma) and assessment time points. One third of the patients (35%) reported clinically significant fatigue, 20%-44% had cognitive complaints, while prevalence of sleep disturbance was not reported. Quality assessment indicated that 80% of the studies were of good quality. CONCLUSION: A large body of research shows that depression and anxiety symptoms are prevalent in melanoma patients before, during and after treatment. However, research examining other symptoms known to affect quality of life, such as fatigue, sleep disturbances, and cognitive problems, is still needed.

The importance of sleep in memory, learning, and other cognitive functions.

Sleep is important for brain health, having both a restorative function and playing an important role in cognitive functions, e.g., attention, memory, learning, and planning. This review finds that sleep disturbances are prevalent and associated with poorer cognitive functioning in neurodegenerative disorders such as Parkinson's disease and in people with non-neurodegenerative diseases such as cancer and mood disorders. Screening for and treating sleep disturbances are potential supplementary approaches to preventing and treating cognitive impairment.

Neurocognitive function and health-related quality of life in a nationwide cohort of long-term childhood brain tumor survivors.

Background: Childhood brain tumor survivors are at high risk of late effects, especially neurocognitive impairment. Limited data are available examining neurocognitive function and associations with quality of life (QoL) in childhood brain tumor survivors. Our aim was to examine neurocognitive function in childhood brain tumor survivors, and associations with QoL and symptom burden. Methods: Five-year survivors of brain tumors over the age of 15 were identified in the Danish Childhood Cancer Registry (n = 423). Eligible and consenting participants completed neuropsychological tests and questionnaires assessing QoL, insomnia, fatigue, anxiety, and depression. Survivors treated with radiation (n = 59) were statistically compared with survivors not treated with radiation (n = 102). Results: In total, 170 survivors participated (40.2% participation rate). Sixty-six percent of the survivors who completed neurocognitive tests (n = 161) exhibited overall neurocognitive impairment. Survivors treated with radiation, especially whole-brain irradiation, exhibited poorer neurocognitive outcomes than survivors not treated with radiation. Neurocognitive outcomes for survivors treated with surgery were below normative expectations. Furthermore, a number of survivors experienced significant fatigue (40%), anxiety (23%), insomnia (13%), and/or depression (6%). Survivors treated with radiation reported lower quality of life (QoL) and higher symptom burden scores than survivors not treated with radiation; particularly in physical functioning, and social functioning with symptoms of fatigue. Neurocognitive impairment was not associated with QoL or symptom burden. Conclusions: In this study, a majority of the childhood brain tumor survivors experienced neurocognitive impairment, reduced QoL, and high symptom burden. Although not associated with each other, it is apparent that childhood brain tumor survivors experience not only neurocognitive dysfunction but may also experience QoL impairments and significant symptom burden.

Circadian disruption and cancer- and treatment-related symptoms.

Cancer patients experience a number of co-occurring side- and late-effects due to cancer and its treatment including fatigue, sleep difficulties, depressive symptoms, and cognitive impairment. These symptoms can impair quality of life and may persist long after treatment completion. Furthermore, they may exacerbate each other's intensity and development over time. The co-occurrence and interdependent nature of these symptoms suggests a possible shared underlying mechanism. Thus far, hypothesized mechanisms that have been purported to underlie these symptoms include disruptions to the immune and endocrine systems. Recently circadian rhythm disruption has emerged as a related pathophysiological mechanism underlying cancer- and cancer-treatment related symptoms. Circadian rhythms are endogenous biobehavioral cycles lasting approximately 24 hours in humans and generated by the circadian master clock - the hypothalamic suprachiasmatic nucleus. The suprachiasmatic nucleus orchestrates rhythmicity in a wide range of bodily functions including hormone levels, body temperature, immune response, and rest-activity behaviors. In this review, we describe four common approaches to the measurement of circadian rhythms, highlight key research findings on the presence of circadian disruption in cancer patients, and provide a review of the literature on associations between circadian rhythm disruption and cancer- and treatment-related symptoms. Implications for future research and interventions will be discussed.

Cancer-related cognitive impairment in non-CNS cancer patients: Targeted review and future action plans in Europe.

Cancer-related cognitive impairment (CRCI) has increasingly been identified over the last two decades in non-CNS system cancer patients. Across Europe, researchers have contributed to this effort by developing preclinical models, exploring underlying mechanisms and assessing cognitive and quality of life changes. The ultimate goal is to develop interventions to treat patients experiencing CRCI. To do so, new challenges need to be addressed requiring the implementation of multidisciplinary research groups. In this consensus paper, we summarize the state of the art in the field of CRCI combined with the future challenges and action plans in Europe. These challenges include data sharing/pooling, standardization of assessments as well as assessing additional biomarkers and neuroimaging investigations, notably through translational studies. We conclude this position paper with specific actions for Europe based on shared scientific expert opinion and stakeholders involved in the Innovative Partnership for Action Against Cancer, with a particular focus on cognitive intervention programs.

Examining the Efficacy of Bright Light Therapy on Cognitive Function in Hematopoietic Stem Cell Transplant Survivors.

Patients who have undergone hematopoietic stem cell transplant (HSCT) may experience cognitive impairment that can persist after treatment. Several studies have shown that bright light therapy may improve cognition, potentially due to its effects on the circadian system via brain regions that respond preferentially to light. In this double-blind randomized controlled trial, the efficacy of bright light therapy on cognition was examined in HSCT survivors. Forty-seven HSCT survivors at an urban hospital in the United States were screened for mild cognitive impairment, randomized to either bright white light (BWL) or comparison dim red light (DRL) conditions using a block randomization approach, and instructed to use their assigned light box every morning upon awakening for 30 min for 4 weeks. Assessments occurred at baseline, the end of the second week of the intervention, the end of the intervention, and at follow-up (8 weeks later). The primary outcome was objective cognitive function as measured by a global composite score on neuropsychological tests. Secondary outcomes included cognitive performance in individual domains, self-reported cognitive function, fatigue, sleep and sleep quality, and circadian rhythm robustness. Repeated-measures linear mixed models for both objective and self-reported cognitive function indicated significant main effects for time (ps < 0.05) suggesting significant improvements in both conditions over time. Time by light condition interaction effects were not significant. Models focused on secondary outcomes yielded no significant effects. Both BWL and DRL groups demonstrated significant improvements in objective cognitive and self-reported cognitive function over time, but there was no hypothesized effect of BWL over DRL nor associations with circadian rhythm robustness. Therapeutic effects of both light conditions, practice effects, and/or placebo effects may account for the findings.Trial registration: ClinicalTrials.gov Identifier: NCT02677987 (9 February 2016).

Sleep and allostatic load: A systematic review and meta-analysis.

The detrimental effects of sleep disturbances on health and wellbeing are well-established but not fully understood. The allostatic load model has been suggested as a framework for understanding the adverse effects of sleep disturbances. We conducted a systematic review and meta-analysis to examine the associations of sleep disturbance and sleep duration with allostatic load. PubMed, PsycINFO, Embase, and Web of Science were searched for records relating to sleep and allostatic load published from 1993 to January 14th, 2022. Two independent raters screened 395 titles and abstracts and 51 full texts. Data were extracted from 18 studies that were assessed for methodological quality. Of these, 17 studies of 26,924 participants were included in the meta-analysis. Sleep disturbance was significantly associated with higher allostatic load (effect size correlation [ESr] = 0.09, p < 0.001), and the association was weaker in samples with a larger proportion of women. When compared to normal sleep, long sleep was significantly associated with higher allostatic load (ESr = 0.12, p = 0.003). Results indicated heterogeneity. No association was found for short sleep (ESr = 0.05, p = 0.069) or sleep duration (ESr = -0.06, p = 0.36). Future research should identify mechanisms and directionality in longitudinal studies.

Optimizing a Behavioral Sleep Intervention for Gynecologic Cancer Survivors: Study Design and Protocol.

Sleep difficulties, particularly symptoms of insomnia and circadian disruption, are among the primary complaints of gynecologic cancer survivors before, during, and after treatment. Moreover, difficulty sleeping has been linked to poorer health-related quality of life and elevated symptom burden in this population. Although leading behavioral sleep interventions have demonstrated efficacy among cancer survivors, up to 50% of survivors are non-adherent to these treatments, likely because these interventions require labor-intensive behavior and lifestyle changes. Therefore, there is a need for more effective and acceptable approaches to diminish sleep disturbance among cancer survivors. This manuscript describes the methodology of a two-part study guided by the Multiphase Optimization Strategy (MOST) framework to identify a streamlined behavioral sleep intervention for gynecologic cancer survivors. Three candidate intervention components previously shown to decrease sleep disturbance will be evaluated, including sleep restriction, stimulus control, and systematic bright light exposure. Participants will be adult women with a history of non-metastatic gynecologic cancer who have completed primary treatment and who report current poor sleep quality. Fifteen participants will be recruited for Part 1 of the study, which will utilize qualitative methods to identify barriers to and facilitators of intervention adherence. Results will inform changes to the delivery of the candidate intervention components to promote adherence in Part 2, where 80 participants will be recruited and randomized to one of eight conditions reflecting every possible combination of the three candidate intervention components in a full factorial design. Participants will complete assessments at baseline, post-intervention, and 3-months post-intervention. Part 2 results will identify the combination of candidate intervention components that yields the most efficacious yet efficient 6-week intervention for diminishing sleep disturbance. This is the first known study to apply the MOST framework to optimize a behavioral sleep intervention and will yield a resource-efficient treatment to diminish sleep disturbance, improve health-related quality of life, and decrease symptom burden among gynecologic cancer survivors. ClinicalTrials.gov Identifier: NCT05044975.

Feasibility and Preliminary Efficacy of a Bright Light Intervention in Ovarian and Endometrial Cancer Survivors.

BACKGROUND: Cancer-related sleep disturbance is common and can adversely affect physical and mental health. Bright light (BL) therapy is a novel intervention that targets sleep by promoting circadian regulation. Emerging evidence suggests BL can improve sleep disturbance, symptom burden, and health-related quality of life in cancer and other populations; however, this research is limited. The present two-phase pilot study assessed the feasibility and preliminary intended effects of BL therapy on sleep in ovarian and endometrial cancer survivors, and explored biologic and chronobiologic factors that may underlie intervention effects. METHODS: In phase I, focus groups were conducted with 12 survivors and 9 gynecologic oncology clinicians to evaluate and gather feedback about the proposed study. In phase II, a pilot randomized controlled trial was conducted with 18 ovarian or endometrial cancer survivors who were randomized 1:1 to receive 45 min of BL or dim light (DL) for 4 weeks. Participants wore wrist actigraphs; completed sleep diaries and self-report questionnaires; and provided blood, saliva, and urine samples at baseline (T1), post-intervention (T2), and 3-month follow-up (T3). RESULTS: Study procedures were modified according to focus group results. Enrollment, retention, and adherence were all ≥ 80%. Mixed-model ANOVAs demonstrated that the number of nighttime awakenings per actigraphy, and sleep quality and depression per self-report, trended toward improvements in the BL condition compared to the DL condition. These variables improved from T1 to T2 before returning to baseline at T3. Effect sizes were generally medium to large. CONCLUSIONS: Study findings suggest that BL therapy is feasible among ovarian and endometrial cancer survivors. It may be an effective, non-pharmacological approach to reduce sleep disturbance and symptom burden in this population.

Long-term cognitive dysfunction after radiation therapy for primary brain tumors.

Background: The extent of radiation therapy (RT)-induced changes in cognitive function is unknown. RT with protons instead of photons spares the healthy brain tissue more and is believed to reduce the risk of cognitive dysfunction. There is modest knowledge on which parts of the brain we need to spare, to prevent cognitive dysfunction. To uncover which cognitive domains is most affected, we compared cognitive functioning in brain tumor patients treated with neurosurgery and RT with brain tumor patients treated with neurosurgery alone. Methods: A cross-sectional study assessing cognitive function in 110 patients with a primary brain tumor grades I-III or medulloblastoma (grade IV) treated at Aarhus University Hospital (AUH), Denmark between 2006 and 2016. Two cohorts were established: a cohort of 81 brain tumor patients who had received neurosurgery followed by RT (RT+), and a cohort of 29 brain tumor patients who had only received neurosurgery (RT-). The patients underwent questionnaires and neuropsychological assessment with standardized tests. Results: Mean age was 53.5 years with an average time since diagnosis of 7.3 years. Compared with normative data, lower average scores were observed for the entire group on domains concerning of verbal learning and memory (p < .001), attention and working memory (p < .001), processing speed (p < .001), and executive functioning (p < .001). Compared to RT- patients, RT + patients scored lower on domains concerning processing speed (p = .04) and executive function (p = .05) and had higher impairment frequency on verbal fluency (p = .02) with 16% of patients exceeding 1.5 SD below normative data. Conclusions: Our results indicate that treatment, including RT, for a primary brain tumor may have negative long-term impact on cognitive function, especially on processing speed and executive function.

Longitudinal dyadic associations of fear of cancer recurrence and the impact of treatment in prostate cancer patients and their spouses.

Background: Fear of cancer recurrence (FCR) in patients and their spouses is associated with reduced quality of life, but little is known about longitudinal dyadic associations of FCR between them. This study examined (i) the trajectory of FCR from pre-treatment to 12 months later; (ii) dyadic associations of FCR over time; and (iii) whether cancer treatment type predicted later FCR among prostate cancer patients and their spouses. Methods: Sixty-nine patients and 71 spouses of patients with localized prostate cancer completed a FCR measure at baseline (pre-treatment), 6 months and 12 months later (post-treatment). A repeated measures linear mixed model was used to examine FCR trajectories. Actor-partner interdependence models (APIMs) were conducted on the 52 couples with complete data to examine actor and partner effects and treatment type on subsequent FCR. Results: Patients and spouses reported moderate FCR levels over time, though spouses' FCR was significantly higher than patients' FCR (p < .001). FCR declined significantly for both groups over time (p < .001). APIMs demonstrated significant actor effects in baseline to 6 month, and 6-12 month models. Surgery was significantly associated with lower spouse FCR at 6 months, and radiation with lower patient FCR at 12 months. Conclusions: This is the first study to have concurrently examined FCR longitudinally in prostate cancer patients and spouses. Patients' and spouses' FCR declined from pre- to post-treatment, with spouses experiencing greater FCR than patients over time. FCR in patients and spouses did not appear to impact one another over time. Treatment type impacted FCR in patients and spouses differently.

Structural brain alterations following adult non-CNS cancers: a systematic review of the neuroimaging literature.

Background: Cancer and cancer treatments may impact the brain through several pathways leading to cognitive impairment. Neuroimaging evidence has begun to elucidate the neurobiological underpinnings of cancer-related cognitive impairment. The aim of this paper was to systematically review available literature on structural brain alterations following adult non-central nervous system (CNS) cancers and associated treatments. Methods: This review followed PRISMA guidelines and was registered in PROSPERO (ID#107387). Comprehensive searches were conducted in June 2018 using PubMed and Web of Science. Inclusion criteria were English peer-reviewed journal articles of formal, controlled studies that examined structural neuroimaging outcomes in adult non-CNS cancer patients and survivors. Selected articles were assessed for quality and risk of bias using the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Results: Thirty-six publications of prospective and cross-sectional studies met inclusion criteria and were included. Structural brain alterations following cancer and its treatment were reported in a majority of the publications as evidenced by reduced global and local gray matter volumes, impaired white matter microstructural integrity, and brain network alterations. Structural alterations were most often evident when cancer-treated groups were compared with healthy controls, and more subtle when compared with cancer controls. Regarding the existence of pretreatment impairments, the evidence was equivocal. There was significant between-study heterogeneity in imaging analytical approaches and use of statistical adjustments. Over half reported associations with cognitive outcomes, though regions and associated cognitive domains were heterogeneous. Conclusions: Structural brain alterations following cancer and cancer treatments were reported in a majority of the reviewed studies. However, the extent of observed alterations depended on the choice of comparison groups. Methodological issues exist that will need to be addressed systematically to ensure the validity of findings. Large-scale prospective studies with extended assessment points are warranted to replicate and build upon initial findings.

A mixed methods analysis of perceived cognitive impairment in hematopoietic stem cell transplant survivors.

OBJECTIVE: Hematopoietic stem cell transplant (HSCT) survivors may show evidence of objective cognitive impairment; however, perceived cognitive problems and their impact on quality of life are less well-understood. The purpose of this study was to explore HSCT survivors' perceptions of cognitive impairment and its effect on daily life functioning. METHOD: Sixty-nine autologous and allogeneic HSCT survivors nine months to three years posttransplant experiencing mild survivorship problems completed a brief structured interview regarding perceived cognitive impairment since transplant. Data were coded and content analyzed. The frequency of participants reporting cognitive problems by domain and associations between reports of cognitive problems and age, depressed mood, anxiety, and health-related quality of life were examined. RESULT: Overall, 49 of the 69 participants (71%) reported cognitive impairments after transplant: 38 in memory (55%), 29 in attention and concentration (42%), and smaller numbers in other domains. There were no significant differences in problems reported by transplant type. Of the 50 participants who worked before transplant, 19 (38%) did not return to work following transplant, with 12 citing cognitive and health problems as being the reason. There were significant associations between reports of cognitive impairment and younger age (p = 0.02), depressed mood (p = 0.02), anxiety (p = 0.002), and health-related quality of life (p = 0.008). SIGNIFICANCE OF RESULTS: A large proportion of survivors reported cognitive impairment following HSCT that impaired daily life functioning. Perceived cognitive impairment was associated with younger age, greater distress and reduced health-related quality of life.

Programmed environmental illumination during autologous stem cell transplantation hospitalization for the treatment of multiple myeloma reduces severity of depression: A preliminary randomized controlled trial.

BACKGROUND: Over a third of multiple myeloma (MM) patients report clinical levels of depression during autologous stem cell transplant (ASCT) hospitalization. We report preliminary results from a randomized clinical trial investigating the effect of Programmed Environmental Illumination (PEI) of hospital rooms on depression. METHODS: Patients (N = 187) scheduled to receive an ASCT were assessed for eligibility. Those who met study eligibility criteria (n = 44) were randomly assigned to one of two PEI conditions involving delivery of either circadian active bright white light (BWL) or circadian inactive dim white light (DWL) throughout the room from 7 to 10 am daily during hospitalization. Patients completed the Center for Epidemiological Studies Depression Scale (CES-D) prior to hospitalization, at days 2 and 7 post-transplant, and on the third day of engraftment. RESULTS: General linear model analyses revealed no difference between the groups in CES-D total score at baseline (P = 0.7859). A longitudinal linear mixed model analysis revealed a significant interaction between time of assessment and light condition [F(3,107) = 2.90; P = 0.0386; ɳ2  = 0.08)], indicating that PEI prevented the development of depression during hospitalization, with effects reaching significance by the third day of engraftment. At the third day of engraftment, 68.4% of the participants in the DWL comparison condition met the criteria for clinically significant depression compared to 42.1% in the BWL condition. CONCLUSION: These findings demonstrate that PEI using BWL during MM ASCT hospitalization is effective in reducing the development of depression. Future studies should examine the mechanisms whereby PEI improves depression.

Advice to patients undergoing stem cell transplant: Content analysis of survivor peer support narratives.

Hematopoietic stem cell transplant survivors often share advice with patients undergoing this difficult treatment. We content analyzed narratives written by 59 transplant survivors given the opportunity to share advice with patients. Analyses described categories of advice they shared and evaluated their perceptions of the helpfulness of advice they had received. We found nine advice categories and evidence for variation in their perceived helpfulness, especially for advice to "be your own advocate," "have someone you can rely on," and "think positive." Findings suggest the need to investigate how seemingly innocuous advice can be unhelpful and potentially distressing to some patients.

Computerized cognitive training in prostate cancer patients on androgen deprivation therapy: a pilot study.

PURPOSE: Prostate cancer patients who have undergone androgen deprivation therapy (ADT) may experience cognitive impairment, yet there is an unmet need for nonpharmacological interventions to address cognitive impairment in this population. This study examines the feasibility, acceptability, and preliminary efficacy of a home-based computerized cognitive training (CCT) program to treat cancer-related cognitive impairment. METHODS: Sixty men who had received ≥ 3 months of ADT were screened for at least mild cognitive or neurobehavioral impairment and randomized to 8 weeks of CCT or usual care. Follow-up assessments occurred immediately post-intervention or equivalent (T2) and 8 weeks later (T3). The acceptability of CCT was also assessed. RESULTS: Feasibility:A priori feasibility thresholds were partially met (i.e., randomization rate > 50%, retention rate > 70% excluding CCT drop-outs, but < 70% for intent-to-treat). Acceptability: Participants were mostly satisfied with CCT and found it somewhat enjoyable, though barriers to uptake existed. Preliminary efficacy: Linear mixed models indicated significant time by group effects favorable to CCT in reaction time (p = .01), but unfavorable to CCT in verbal and visual memory (ps < .05). Memory was temporarily suppressed in the CCT group at T2, but normalized by T3. There was no effect of CCT on self-reported cognitive functioning, neurobehavioral functioning, nor quality of life. CONCLUSIONS: This study provides tentative support for the feasibility and acceptability of CCT to treat mild cognitive impairment in ADT patients. CCT had a beneficial effect on reaction time, but temporarily suppressed memory. CCT's benefits may be limited to a narrow area of functioning. Larger-scale studies are needed.

The Effect of Systematic Light Exposure on Sleep in a Mixed Group of Fatigued Cancer Survivors.

STUDY OBJECTIVES: Sleep disturbances are commonly reported by cancer survivors. Systematic light exposure using bright light has been used to improve sleep in other populations. In this secondary data analysis, the effect of morning administration of bright light on sleep and sleep quality was examined in a mixed group of fatigued cancer survivors. METHODS: Forty-four cancer survivors screened for cancer-related fatigue were randomized to either a bright white light or a comparison dim red light condition. Participants were instructed to use a light box every morning for 30 minutes for 4 weeks. Wrist actigraphy and the Pittsburgh Sleep Quality Index were administered at 4 time points: prior to light treatment (baseline), 2 weeks into the intervention, during the last week of the intervention, and 3 weeks postintervention. Thirty-seven participants completed the end-of-intervention assessment. RESULTS: Repeated-measures linear mixed models indicated a statistically significant time × treatment group interaction effect with sleep efficiency improving more in the bright light condition over time compared with the dim light condition (F3,42 = 5.55; P = .003) with a large effect size (partial η2 = 0.28). By the end of the intervention and 3 weeks postintervention, mean sleep efficiency in the bright light group was in the normal range. Medium to large effect sizes were also seen in sleep quality, total sleep time, and wake after sleep onset for participants favoring the bright light condition. CONCLUSIONS: The results suggest that systematic bright light exposure in the morning may have beneficial effects on sleep in fatigued cancer survivors. Larger scale efficacy trials are warranted. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov, Title: Treating Cancer-Related Fatigue Through Systematic Light Exposure, Identifier: NCT01873794, URL: https://clinicaltrials.gov/ct2/show/NCT01873794.