Mechanisms of sleep disturbances in long-term cancer survivors: a childhood cancer survivor study report.

BACKGROUND: Sleep problems following childhood cancer treatment may persist into adulthood, exacerbating cancer-related late effects and putting survivors at risk for poor physical and psychosocial functioning. This study examines sleep in long-term survivors and their siblings to identify risk factors and disease correlates. METHODS: Childhood cancer survivors (≥5 years from diagnosis; n = 12 340; 51.5% female; mean [SD] age = 39.4 [9.6] years) and siblings (n = 2395; 57.1% female; age = 44.6 [10.5] years) participating in the Childhood Cancer Survivor Study completed the Pittsburgh Sleep Quality Index (PSQI). Multivariable Poisson-error generalized estimating equation compared prevalence of binary sleep outcomes between survivors and siblings and evaluated cancer history and chronic health conditions (CHC) for associations with sleep outcomes, adjusting for age (at diagnosis and current), sex, race/ethnicity, and body mass index. RESULTS: Survivors were more likely to report clinically elevated composite PSQI scores (>5; 45.1% vs 40.0%, adjusted prevalence ratio [PR] = 1.20, 95% CI = 1.13 to 1.27), symptoms of insomnia (38.8% vs 32.0%, PR = 1.26, 95% CI = 1.18 to 1.35), snoring (18.0% vs 17.4%, PR = 1.11, 95% CI = 1.01 to 1.23), and sleep medication use (13.2% vs 11.5%, PR = 1.28, 95% CI = 1.12 to 1.45) compared with siblings. Within cancer survivors, PSQI scores were similar across diagnoses. Anthracycline exposure (PR = 1.13, 95% CI = 1.03 to 1.25), abdominal radiation (PR = 1.16, 95% CI = 1.04 to 1.29), and increasing CHC burden were associated with elevated PSQI scores (PRs = 1.21-1.48). CONCLUSIONS: Among survivors, sleep problems were more closely related to CHC than diagnosis or treatment history, although longitudinal research is needed to determine the direction of this association. Frequent sleep-promoting medication use suggests interest in managing sleep problems; behavioral sleep intervention is advised for long-term management.

Cancer Survivorship at Stanford Cancer Institute.

The Stanford Cancer Survivorship Program is a key initiative of Stanford Cancer Institute. The program's mission is to improve the experience and outcomes of patients and family caregivers throughout all phases of the cancer trajectory by advancing survivorship research, clinical care, and education. The four pillars of the program include clinical care delivery with a focus on primary care-survivorship collaboration and expanding specialty services, education and training of healthcare professionals, transdisciplinary patient-oriented research, and community engagement. Cross-cutting areas of expertise include the following: (a) adolescents and young adults (AYAs), (b) mental health and patient self-management, (c) integration of primary care, and (d) postgraduate medical education. The clinical care model includes embedded survivorship clinics within disease groups in outpatient clinics, novel clinics designed to address unmet needs such as sexual health for women, and primary care-based faculty-led survivorship clinics for patients undergoing active cancer care requiring co-management, those who have completed active therapy and those at high risk for cancer due to genetic risk. Educational initiatives developed to date include an online course and medical textbook for primary care clinicians, a lecture series, monthly research team meetings, and rotations for medical trainees. Patient-facing activities include webinars and a podcast series designed to promote awareness, thus expanding the provision of expert-vetted information. Ongoing research focuses on oncofertility and family building after cancer, improving communication for AYAs, changing mindsets to improve quality of life through targeted digital interventions, increasing capacity to care for cancer survivors, and strengthening collaboration with community partners. IMPLICATIONS FOR CANCER SURVIVORS: Stanford's Cancer Survivorship Program includes a robust transdisciplinary and interdisciplinary research, training and clinical platform that is committed to advancing access and improving care for people living with and beyond cancer, through innovation in design and care delivery.

Neuroimaging based biotypes for precision diagnosis and prognosis in cancer-related cognitive impairment.

Cancer related cognitive impairment (CRCI) is commonly associated with cancer and its treatments, yet the present binary diagnostic approach fails to capture the full spectrum of this syndrome. Cognitive function is highly complex and exists on a continuum that is poorly characterized by dichotomous categories. Advanced statistical methodologies applied to symptom assessments have demonstrated that there are multiple subclasses of CRCI. However, studies suggest that relying on symptom assessments alone may fail to account for significant differences in the neural mechanisms that underlie a specific cognitive phenotype. Treatment plans that address the specific physiologic mechanisms involved in an individual patient's condition is the heart of precision medicine. In this narrative review, we discuss how biotyping, a precision medicine framework being utilized in other mental disorders, could be applied to CRCI. Specifically, we discuss how neuroimaging can be used to determine biotypes of CRCI, which allow for increased precision in prediction and diagnosis of CRCI via biologic mechanistic data. Biotypes may also provide more precise clinical endpoints for intervention trials. Biotyping could be made more feasible with proxy imaging technologies or liquid biomarkers. Large cross-sectional phenotyping studies are needed in addition to evaluation of longitudinal trajectories, and data sharing/pooling is highly feasible with currently available digital infrastructures.

Behavioral and biologic characteristics of cancer-related cognitive impairment biotypes.

Psychiatric diagnosis is moving away from symptom-based classification and towards multi-dimensional, biologically-based characterization, or biotyping. We previously identified three biotypes of chemotherapy-related cognitive impairment based on functional brain connectivity. In this follow-up study of 80 chemotherapy-treated breast cancer survivors and 80 non-cancer controls, we evaluated additional factors to help explain biotype expression: neurofunctional stability, brain age, apolipoprotein (APOE) genotype, and psychoneurologic symptoms. We also compared the discriminative ability of a traditional, symptom-based cognitive impairment definition with that of biotypes. We found significant differences in cortical brain age (F = 10.50, p < 0.001), neurofunctional stability (F = 2.83, p = 0.041), APOE e4 genotype (X2 = 7.68, p = 0.050), and psychoneurological symptoms (Pillai = 0.378, p < 0.001) across the three biotypes. The more resilient Biotype 2 demonstrated significantly higher neurofunctional stability compared to the other biotypes. Symptom-based classification of cognitive impairment did not differentiate biologic or other behavioral variables, suggesting that traditional categorization of cancer-related cognitive effects may miss important characteristics which could inform targeted treatment strategies. Additionally, biotyping, but not symptom-typing, was able to distinguish survivors with cognitive versus psychological effects. Our results suggest that Biotype 1 survivors might benefit from first addressing symptoms of anxiety and fatigue, Biotype 3 might benefit from a treatment plan which includes sleep hygiene, and Biotype 2 might benefit most from cognitive skills training or rehabilitation. Future research should include additional demographic and clinical information to further investigate biotype expression related to risk and resilience and examine integration of more clinically feasible imaging approaches.

International Survey of Pediatric Oncologists' Beliefs and Communication Practices Regarding Symptom Self-Monitoring by Childhood Cancer Survivors.

PURPOSE: Childhood cancer survivors report self-monitoring for and worrying about symptoms of disease recurrence and secondary cancers, although symptom-related worry is associated with poorer health-related quality of life. This survey captured pediatric oncologists' beliefs and communication practices regarding symptom self-monitoring for childhood cancer survivors. METHODS: Using a closed-loop snowball sampling technique, pediatric oncologists completed an online survey regarding the importance of symptom self-monitoring for off-therapy patients, the degree to which symptom self-monitoring was perceived to cause stress and worry, and communication practices. RESULTS: 196 pediatric oncologists (White [78%]; female [64%]; Mage = 47 years) from every continent except Antarctica participated. Oncologists believed it is important for off-therapy patients to self-monitor for symptoms of cancer recurrence (90%) and treatment late effects (94%), although some noted that recurrence (30%) and late effects (55%) are typically detected by routine surveillance before symptoms appear. Oncologists varied in their beliefs that off-therapy patients do (31%) or do not (31%) worry unnecessarily about symptoms of recurrence. Two thirds (62%) of oncologists reported often/always discussing with off-therapy patients which symptoms could indicate cancer recurrence, whereas fewer than half (43%) often/always discussed which symptoms were unlikely to indicate recurrence. Oncologists identified a need for education regarding how to communicate around symptom self-monitoring and the potential utility of a screening tool to identify those who worry excessively. CONCLUSION: Despite nearly universal belief that their off-therapy patients should self-monitor for symptoms of disease recurrence and late effects, a substantial proportion of pediatric oncologists do not counsel patients on symptom self-monitoring. Since nearly one-third believe that off-therapy patients worry unnecessarily about symptoms of recurrence, improving patient education regarding which symptoms are and are not medically concerning could decrease stress and improve health-related quality of life for pediatric cancer survivors.

Symptoms and survivorship needs differences between "good sleepers" and "bad sleepers" in survivors of breast and gynecologic cancers.

INTRODUCTION: Although 80% of cancer survivors report symptoms of insomnia, only 28-43% meet DSM-5 criteria for this diagnosis. We sought to characterize the association between patient-reported insomnia symptoms, patient outcomes, and supportive care variables, as well as explore clinically meaningful insomnia thresholds in a sample of women diagnosed with breast and gynecologic cancers. METHODS: From July 2018-March 2019, all breast and gynecologic cancer survivors seen at the Stanford Women's Cancer Center were approached and invited to participate in the study (15% declined). Of those who consented, 273 survivors completed an online survey related to their sleep (ISI), quality of life (FACT-G), distress (PHQ-4), supportive care needs (SCNS-SF34), and symptom severity (MDASI). Survivors who scored <8 on ISI were categorized as "good sleepers," survivors with ISI ≥8 were categorized as "bad sleepers." RESULTS: 126 (46.2%) of survivors were "good sleepers," 147 (53.8%) were "bad sleepers." Good sleepers were older than bad sleepers (p < .05) but did not differ in any other demographic or any medical variables. Using hierarchical linear regression models, we found that good sleep (ISI <8) was associated with higher quality of life, lower psychological distress, increased social support, lower symptom severity, and lower supportive care needs, after accounting for demographic, medical, and treatment variables. The findings were largely replicated with an ISI cut off of 15. CONCLUSIONS: Among women treated for breast and gynecologic cancers, survivors who were good sleepers had better psychosocial outcomes, fewer supportive care needs, and lower symptom severity compared to those who reported insomnia symptoms. Results also indicate that degree of sleep impairment, whether mild or severe, has similarly poor associations with most aspects of patient functioning and symptomatic burden. Further research is needed to determine causality of these findings.

Examining Associations Among Sexual Health, Unmet Care Needs, and Distress in Breast and Gynecologic Cancer Survivors.

OBJECTIVES: This study evaluated breast and gynecologic cancer patients' sexual function, unmet needs related to sexuality, and distress. DATA SOURCES: Secondary analyses of a cross-sectional survey study evaluated measures of sexual function (Female Sexual Function Index [FSFI]), unmet needs (Supportive Care Needs Scale), and distress (Patient Health Questionnaire). χ2 test, t tests, and analysis of variances (ANOVAs) tested bivariate relationships. Subgroup comparisons were made based on the Female Sexual Function Index sexual dysfunction diagnostic cut-off score (<26.55; lower scores indicate greater dysfunction). A regression model tested associations between sexual function and unmet needs with distress as the outcome variable. CONCLUSION: Clinically significant sexual dysfunction was common in this cohort of women. In multivariate modeling, worse sexual function and greater unmet sexuality needs related to greater distress. Future work should explore reasons behind the high levels of sexual dysfunction and unmet needs in female survivors. IMPLICATIONS FOR NURSING PRACTICE: It is important to routinely screen for sexual health concerns among female cancer survivors at all phases of the cancer trajectory including years posttreatment.

Association of illness mindsets with health-related quality of life in cancer survivors.

OBJECTIVE: This study aimed to examine the association between mindsets-established, but mutable beliefs that a person holds-and health-related quality of life in survivors of breast and gynecologic cancer. METHOD: A cross-sectional survey study was conducted with breast and gynecologic cancer survivors. Measures included the Illness Mindset Questionnaire and Functional Assessment of Cancer Therapy-General (FACT-G). RESULTS: Two hundred seventy-three survivors (74% breast/26% gynecologic) who were on average 3.9 years post-diagnosis (SD = 4.2), Mage 55 (SD = 12) completed the survey (response rate 80%). Of the survivors, 20.1% (N = 55) endorsed ("agree" or "strongly agree") that Cancer is a Catastrophe, 52.4% (N = 143) endorsed that Cancer is Manageable, and 65.9% (N = 180) endorsed that Cancer can be an Opportunity (not mutually exclusive). Those who endorsed a maladaptive mindset (Cancer is a Catastrophe) reported lower health-related quality of life (HRQOL) compared with those who did not hold this belief (p < .001). Alternatively, those who endorsed more adaptive mindsets (Cancer is Manageable or Cancer can be an Opportunity) reported better HRQOL compared with those who disagreed (all p-values < .05). All three mindsets were independent correlates of HRQOL, explaining 6-15% unique variance in HRQOL, even after accounting for demographic and medical factors. CONCLUSIONS: Mindsets about illness are significantly associated with HRQOL in cancer survivors. Our data come from a one-time evaluation of cancer survivors at a single clinic and provide a foundation for future longitudinal studies and RCTs on the relationship between mindsets and psychosocial outcomes in cancer survivors. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Greater financial toxicity relates to greater distress and worse quality of life among breast and gynecologic cancer survivors.

BACKGROUND: Financial toxicity includes distress and burden from cancer-related costs. Women are more likely to experience worse cancer-related financial outcomes than men. This study evaluated breast and gynecologic cancer patients' subjective experiences of financial toxicity and associations with distress and quality of life (QOL). METHODS: A cross-sectional survey study included measures of financial toxicity (Comprehensive Score for Financial Toxicity [COST] Version 2), distress (Patient Health Questionnaire), and QOL (Functional Assessment of Cancer Therapy). Chi-square, t-tests, and ANOVAs examined bivariate relationships. Two regression models tested associations between financial toxicity and distress and QOL, controlling for covariates. Financial toxicity subgroups were compared based on a validated grading system. RESULTS: Participants (N = 273; 74% breast cancer) averaged 54.65 years (SD = 12.08), were 3.42 years (SD = 4.20) post-diagnosis, and 33% reported cancer-related change in employment status. Financial toxicity was "mild" overall (COST M = 26.11, SD = 11.14); 32% worried about cancer-related financial problems (quite a bit/very much; item-level analysis). Worse financial toxicity related to younger age (p < 0.001), identifying as a non-Asian minority (p = 0.03) or Hispanic (p = 0.01), being single (p < 0.001), lower education (p = 0.004), lower income (p < 0.001), late-stage disease (p = 0.001), recurrent disease (p = 0.004), and active treatment (p < 0.001). In separate multivariable models, greater financial toxicity related to greater distress (ß = -0.45 p < 0.001) and worse QOL (ß = 0.58, p < 0.001). Financial toxicity subgroups reported clinically significant differences in distress and QOL (p's < 0.05). CONCLUSIONS: Cancer-related financial burden is associated with pervasive negative effects and may impact subgroups differently. Future research should explore financial experiences across subgroups, aiming to better identify those at risk and build targeted interventions.

Relationship between physical activity, objective sleep parameters, and circadian rhythm in patients with head and neck cancer receiving chemoradiotherapy: A longitudinal study.

OBJECTIVES: This study was developed to assess the relationship between physical activity, sleep and circadian rhythm using accelerometer and urine melatonin levels in patients with head and neck cancer (HNC). Also, this study evaluated the changes in physical activity, sleep, and circadian rhythm during the seven-week course of chemoradiotherapy. METHODS: This longitudinal study recruited 27 participants diagnosed with HNC who were planning to undergo chemoradiotherapy. Accelerometers worn for 3 days during the 1st, 3rd, and 7th weeks of chemoradiotherapy were used to assess physical activity levels (step count and metabolic equivalents [METs]) and sleep quality (total sleep time [TST], sleep onset latency [SOL], and sleep efficiency [SE]). Urine melatonin analysis was conducted using the morning void urine sample on 1st, 3rd, and 7th weeks. The change in variables during the seven weeks and the correlation between them were analyzed. RESULTS: During the seven weeks, trends of reduction in variables of physical activity, sleep and circadian rhythm were observed with significant decrease in step count, TST and melatonin levels. SE was found to have strong negative correlation with physical activity. TST was found to have moderate correlation with SE and step count. The variables of physical activity also showed moderate correlation among them. CONCLUSION: This study concludes that higher physical activity is associated with poor SE due to increased night-time activity. There was a significant reduction in physical activity and sleep observed during seven weeks with moderate association between them. The significant circadian rhythm deregulation however showed poor association with the other variables.Level of Evidence: 2b.

Cross-Sectional Characterization of Local Brain Network Connectivity Pre and Post Breast Cancer Treatment and Distinct Association With Subjective Cognitive and Psychological Function.

Objective: We aimed to characterize local brain network connectivity in long-term breast cancer survivors compared to newly diagnosed patients. Methods: Functional magnetic resonance imaging (fMRI) and subjective cognitive and psychological function data were obtained from a group of 76 newly diagnosed, pre-treatment female patients with breast cancer (mean age 57 ± 7 years) and a separate group of 80, post-treatment, female breast cancer survivors (mean age 58 ± 8; mean time since treatment 44 ± 43 months). The network-based statistic (NBS) was used to compare connectivity of local brain edges between groups. Hubs were defined as nodes with connectivity indices one standard deviation or more above network mean and were further classified as provincial (higher intra-subnetwork connectivity) or connector (higher inter-subnetwork connectivity) using the participation coefficient. We determined the hub status of nodes encompassing significantly different edges and correlated the centralities of edges with behavioral measures. Results: The post-treatment group demonstrated significantly lower subjective cognitive function (W = 3,856, p = 0.004) but there were no group differences in psychological distress (W = 2,866, p = 0.627). NBS indicated significantly altered connectivity (p < 0.042, corrected) in the post-treatment group compared to the pre-treatment group largely in temporal, frontal-temporal and temporal-parietal areas. The majority of the regions projecting these connections (78%) met criteria for hub status and significantly less of these hubs were connectors in the post-treatment group (z = 1.85, p = 0.031). Subjective cognitive function and psychological distress were correlated with largely non-overlapping edges in the post-treatment group (p < 0.05). Conclusion: Widespread functional network alterations are evident in long-term survivors of breast cancer compared to newly diagnosed patients. We also demonstrated that there are both overlapping and unique brain network signatures for subjective cognitive function vs. psychological distress.

Headache outcomes of a sleep behavioral intervention in breast cancer survivors: Secondary analysis of a randomized clinical trial.

BACKGROUND: Breast cancer survivors often have persisting headache. In a secondary analysis of the Brief Behavioral Therapy for Cancer-Related Insomnia (BBT-CI) clinical trial (ClinicalTrials.gov identifier NCT02165839), the authors examined the effects of BBT-CI on headache outcomes in patients with breast cancer. METHODS: Patients with breast cancer who were receiving chemotherapy were randomly assigned to receive either the BBT-CI intervention or the Healthy EAting Education Learning for healthy sleep (HEAL) control intervention, and both were delivered over 6 weeks by trained staff. Headache outcomes and heart rate variability (HRV) were measured at baseline, 6 weeks, 6 months, and 12 months. Mixed-effects models were used to examine longitudinal headache outcomes in the groups according to the intention to treat. Principal component analysis and agglomerative hierarchical clustering were conducted to reduce 16 variables for data-driven phenotyping. RESULTS: Patients in the BBT-CI arm (n = 73) exhibited a significant reduction in headache burden over time (P = .02; effect size [Cohen d] = 0.43), whereas the reduction was not significant among those in the HEAL arm (n = 66). The first principal component was positively loaded by headache, sleep, fatigue, and nausea/vomiting and was negatively loaded by cognitive, physical, and emotional functioning. Agglomerative hierarchical clustering revealed 3 natural clusters. Cluster I (n = 58) featured the highest burden of headache, insomnia, and nausea/vomiting; cluster II (n = 50) featured the lowest HRV despite a low burden of headache and insomnia; and cluster III (n = 31) showed an inverse relation between HRV and headache-insomnia, signifying autonomic dysfunction. CONCLUSIONS: BBT-CI is efficacious in reducing headache burden in breast cancer survivors. Patient phenotyping demonstrates a headache type featuring sleep disturbance, nausea/vomiting, and low physical functioning-revealing similarities to migraine. LAY SUMMARY: Breast cancer survivors often have persisting headache symptoms. In patients with cancer, treatment of chronic headache disorders using daily medications may be challenging because of drug interactions with chemotherapy and other cancer therapies as well as patients' reluctance to add more drugs to their medicine list. Headache and sleep disorders are closely related to each other. This study demonstrates that a sleep behavioral therapy reduced headache burden in breast cancer survivors. In addition, the majority of headache sufferers had a headache type with similarities to migraine-featuring sleep disturbance, nausea/vomiting, and low physical functioning.

Development of a Mobile Health App (TOGETHERCare) to Reduce Cancer Care Partner Burden: Product Design Study.

BACKGROUND: Approximately 6.1 million adults in the United States serve as care partners for cancer survivors. Studies have demonstrated that engaging cancer survivors and their care partners through technology-enabled structured symptom collection has several benefits. Given the high utilization of mobile technologies, even among underserved populations and in low resource areas, mobile apps may provide a meaningful access point for all stakeholders for symptom management. OBJECTIVE: We aimed to develop a mobile app incorporating user preferences to enable cancer survivors' care partners to monitor the survivors' health and to provide care partner resources. METHODS: An iterative information gathering process was conducted that included (1) discussions with 138 stakeholders to identify challenges and gaps in survivor home care; (2) semistructured interviews with clinicians (n=3), cancer survivors (n=3), and care partners (n=3) to identify specific needs; and (3) a 28-day feasibility field test with seven care partners. RESULTS: Health professionals noted the importance of identifying early symptoms of adverse events. Survivors requested modules on medication, diet, self-care, reminders, and a version in Spanish. Care partners preferred to focus primarily on the patient's health and not their own. The app was developed incorporating quality-of-life surveys and symptom reporting, as well as resources on home survivor care. Early user testing demonstrated ease of use and app feasibility. CONCLUSIONS: TOGETHERCare, a novel mobile app, was developed with user input to track the care partner's health and report on survivor symptoms during home care. The following two clinical benefits emerged: (1) reduced anxiety among care partners who use the app and (2) the potential for identifying survivor symptoms noted by the care partner, which might prevent adverse events. TRIAL REGISTRATION: ClinicalTrials.gov NCT04018677; https://clinicaltrials.gov/ct2/show/NCT04018677.

Patterns of social media use and associations with psychosocial outcomes among breast and gynecologic cancer survivors.

PURPOSE: We sought to characterize the use of social media (SM) among breast and gynecologic cancer survivors, as well as associations between patterns of SM use and psychosocial outcomes. METHODS: Two hundred seventy-three breast and gynecologic cancer survivors recruited at the Stanford Women's Cancer Center completed the study. Participants completed questionnaires to measure quality of life (FACT-G), functional social support (Duke-UNC FSSQ), distress (PHQ-4), decision regret (DRS), and SM use. RESULTS: In total, 75.8% of the sample reported using SM. There was no difference in quality of life (QOL), functional social support (FSS), distress, or decision regret between SM users and non-users. SM users indicated using SM for social support (34.3%) and loneliness (24.6%) more than for information-seeking (15.9%), coping (18.8%), or self-disclosure (14%). SM use for coping was associated with lower QOL (p < .001), lower FSS (p < .001), and higher decision regret (p = .029). Use for social support was associated with lower FSS (p = .029). Use for information seeking was associated with lower QOL (p = .012). Use of SM when lonely was associated with lower QOL (p < .001), higher distress (p = .007), lower FSS (p < .001), and higher decision regret (p = .020). CONCLUSIONS: Associations between SM use and psychosocial outcomes are nuanced and dependent on motivation for use. Further research is needed to better characterize SM use and associations with psychosocial outcomes among cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: SM is an important potential avenue for understanding and addressing the psychosocial effects associated with cancer survivorship.

Does circadian rhythm influence gastrointestinal toxicity?

PURPOSE OF REVIEW: The current review outlines the existing research on the impact of circadian rhythm on gastrointestinal toxicity associated with cancer treatment and explores clinical evidence for utilizing circadian-based approaches in addressing gastrointestinal symptoms such as nausea, vomiting, diarrhea, mucositis, and hepatotoxicity. RECENT FINDINGS: Recent evidence highlights circadian control of gastrointestinal physiology of appetite, digestion, nutrient absorption, and cellular proliferation in the digestive system. In addition, animal models support the mechanistic rationale of using chronotherapy (a type of anticancer therapy delivered at specific times with the goal of producing less toxicity and greater treatment response) to minimize gastrointestinal-impact of systemic cancer treatments. In addition, earlier research demonstrates that many chemotherapeutic agents are responsive to circadian timing in animals. On the contrary, clinical trials focused on minimizing gastrointestinal toxicity using chronotherapy have been limited in recent years and have not yielded the efficacy initially hoped for. Instead, researchers focused on understanding circadian rhythm's influence on the gastrointestinal system at a mechanistic level as well as measuring circadian rhythm at an individual level. SUMMARY: Although using circadian timing is a promising target for reducing gastrointestinal toxicity, recent evidence suggests that more research is needed to understand circadian rhythm before circadian-based interventions can be developed that will result in lessening of gastrointestinal toxicity.

A novel approach to management of sleep-associated problems in patients with breast cancer (MOSAIC) during chemotherapy : A pilot study.

STUDY OBJECTIVES: This pilot randomized controlled trial (RCT) was conducted to assess the preliminary effects of Brief Behavioral Therapy for Cancer-Related Insomnia (BBT-CI) delivered by trained research staff in comparison to a sleep hygiene pamphlet control and to assess moderators of treatment effect in patients with breast cancer undergoing chemotherapy. METHODS: Of 74 participants recruited, 37 were randomized to BBT-CI and 37 were randomized to the control condition. Trained staff members delivered the intervention during chemotherapy treatments to reduce patients' burden. Insomnia was assessed with the Insomnia Severity Index (ISI), anxiety was assessed with the Spielberger State-Trait Anxiety Inventory, symptom burden was assessed with the Symptom Inventory (SI), and study staff recorded previous treatments and surgeries received by patients. RESULTS: Patients randomized to BBT-CI showed significantly greater improvements in their ISI scores compared to the sleep hygiene group. Additionally, several treatment moderators were identified. The effect of BBT-CI was greater among individuals with lower baseline state-trait anxiety, with previous surgery for cancer, and with higher baseline somatic symptom severity. CONCLUSIONS: BBT-CI shows preliminary efficacy compared to the sleep hygiene handout on insomnia in cancer patients undergoing chemotherapy. A large-phase III RCT needs to be conducted to replicate the preliminary findings.

Functional connectome biotypes of chemotherapy-related cognitive impairment.

PURPOSE: Cancer-related cognitive impairment (CRCI) is a common neurotoxicity among patients with breast and other cancers. Neuroimaging studies have demonstrated measurable biomarkers of CRCI but have largely neglected the potential heterogeneity of the syndrome. METHODS: We used retrospective functional MRI data from 80 chemotherapy-treated breast cancer survivors to examine neurophysiologic subtypes or "biotypes" of CRCI. The breast cancer group consisted of training (N = 57) and validation (N = 23) samples. RESULTS: An unsupervised clustering approach using connectomes from the training sample identified three distinct biotypes. Cognitive performance (p < 0.05, corrected) and regional connectome organization (p < 0.001, corrected) differed significantly between the biotypes and also from 103 healthy female controls. We then built a random forest classifier using connectome features to distinguish between the biotypes (accuracy = 91%) and applied this to the validation sample to predict biotype assignment. Cognitive performance (p < 0.05, corrected) and regional connectome organization (p < 0.005, corrected) differed significantly between the predicted biotypes and healthy controls. Biotypes were also characterized by divergent clinical and demographic factors as well as patient reported outcomes. CONCLUSIONS: Neurophysiologic biotypes may help characterize the heterogeneity associated with CRCI in a data-driven manner based on neuroimaging biomarkers. IMPLICATIONS FOR CANCER SURVIVORS: Our novel findings provide a foundation for detecting potential risk and resilience factors that warrant further study. With further investigation, biotypes might be used to personalize assessments of and interventions for CRCI.

Cortical Brain Age from Pre-treatment to Post-chemotherapy in Patients with Breast Cancer.

Chemotherapy-related cognitive impairment and associated brain changes may reflect accelerated brain aging; however, empirical evidence for this theory is limited. The purpose of this study was to measure brain aging in newly diagnosed patients with breast cancer treated with chemotherapy (n = 43) and compare its longitudinal change to that of controls (n = 50). Brain age indices, derived from cortical measures, were compared between women with breast cancer and matched healthy controls across 3 timepoints (time 1: pre-surgery, time 2: 1 month following chemotherapy completion, and time 3: 1-year post-chemotherapy). The breast cancer group showed a significant decrease in cortical thickness across the 3 timepoints (p < .001) and a trend towards significant increase in predicted brain age especially from pre-treatment (time 1) to post-chemotherapy (time 2) compared to controls (p = 0.08). Greater increase in predicted brain age was related to several clinical factors (HER-2 status, surgery type, and history of neoadjuvant chemotherapy) and greater decrease in cortical thickness was associated with greater decrease in performance on a verbal learning task from time 1 to time 3 (r = - 0.48, p < .01). This study demonstrated evidence of increased cortical brain aging in middle-aged patients with breast cancer following chemotherapy treatment that was associated with decreased verbal memory performance.

Predicting Patient Reported Outcomes of Cognitive Function Using Connectome-Based Predictive Modeling in Breast Cancer.

Being able to predict who will likely experience cancer related cognitive impairment (CRCI) could enhance patient care and potentially reduce economic and human costs associated with this adverse event. We aimed to determine if post-treatment patient reported CRCI could also be predicted from baseline resting state fMRI in patients with breast cancer. 76 newly diagnosed patients (n = 42 planned for chemotherapy; n = 34 not planned for chemotherapy) and 50 healthy female controls were assessed at 3 times points [T1 (prior to treatment); T2 (1 month post chemotherapy); T3 (1 year after T2)], and at yoked intervals for controls. Data collection included self-reported executive dysfunction, memory function, and psychological distress and resting state fMRI data converted to connectome matrices for each participant. Statistical analyses included linear mixed modeling, independent t tests, and connectome-based predictive modeling (CPM). Executive dysfunction increased over time in the chemotherapy group and was stable in the other two groups (p < 0.001). Memory function decreased over time in both patient groups compared to controls (p < 0.001). CPM models successfully predicted executive dysfunction and memory function scores (r > 0.31, p < 0.002). Support vector regression with a radial basis function (SVR RBF) showed the highest performance for executive dysfunction and memory function (r = 0.68; r = 0.44, p's < 0.001). Baseline neuroimaging may be useful for predicting patient reported cognitive outcomes which could assist in identifying patients in need of surveillance and/or early intervention for treatment-related cognitive effects.

Distress Management, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology.

Distress is defined in the NCCN Guidelines for Distress Management as a multifactorial, unpleasant experience of a psychologic (ie, cognitive, behavioral, emotional), social, spiritual, and/or physical nature that may interfere with the ability to cope effectively with cancer, its physical symptoms, and its treatment. Early evaluation and screening for distress leads to early and timely management of psychologic distress, which in turn improves medical management. The panel for the Distress Management Guidelines recently added a new principles section including guidance on implementation of standards of psychosocial care for patients with cancer.