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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.

PURPOSE: Older cancer patients are susceptible to long-term effects of chemotherapy, including cancer-related cognitive decline and impairments to quality of life. Taxane-based chemotherapies are associated with physical declines among older women and may negatively impact cognitive performance. We sought to examine whether changes in objective and subjective measures of cognitive performance and well-being differ among older breast cancer survivors as a function of taxane-based chemotherapy treatment regimens. METHODS: Individual-level data was pooled and harmonized from two large prospective studies of older (greater than 60 years) breast cancer survivors. Assessments were conducted prior to systemic therapy and up to 36-months after. Cognitive performance was assessed with objective (working memory, processing speed and executive functions) and subjective tests and physical, emotional and functional well-being was also assessed. RESULTS: One hundred and sixty-seven (M age = 67.3 years) women, with 116 receiving chemotherapy with taxanes and 51 without taxanes contributed data. Declines in subjective cognition for both groups were significant between pre-treatment and 12-month follow-up. Significant improvements were seen on a measure of objective cognition (working memory) from 12 to 36-months. Measures of well-being improved from prior to systemic therapy to 12-months. Longitudinal changes across all measures did not vary as a function of receipt of taxane-based treatment. CONCLUSION: Older women who received treatment with taxanes did not have greater declines in cognitive performance or well-being than women receiving other chemotherapy regimens. Despite older cancer survivors being at greater risk for negative outcomes, treatment with taxane-based chemotherapies does not appear to exacerbate these health consequences.

Introduction Chimeric antigen receptor T-cell (CAR T) therapy offers a potentially curative option for patients with relapsed and refractory hematologic malignancies, including diffuse large B-cell lymphoma (DLBCL). Patient-reported experiences with CAR T therapy are limited and have not been well characterized. The purpose of this qualitative study was to explore patient descriptions of key domains of health-related quality of life (HRQoL) in DLBCL patients treated with CAR T therapy. Methods A targeted literature review was initially conducted to inform the development of the interview guide comprising predetermined open-ended questions. Two focus groups were conducted with a total of 18 patients with DLBCL identified from patient advisory boards. Focus group sessions were recorded and transcribed verbatim. MAXQDA 18.2.0 qualitative data analysis software was utilized to facilitate a constant-comparative coding process to identify key concepts. Results Eight domain impairments (social functioning, emotional functioning, fatigue, physical functioning, cognitive functioning, role functioning, sleep, and pain/discomfort) were identified from the qualitative analysis and endorsed by DLBCL patients treated with CAR T. Compared with before CAR T therapy, patients reported increased impairment in every domain during or immediately after CAR T therapy. This impairment improved for each domain 6 months after CAR T therapy except for pain/discomfort. Compared with before CAR T therapy, improvement in impairment for each domain was observed 6 months after CAR T therapy except for fatigue, sleep, and pain/discomfort. Conclusion This study provides meaningful information regarding the impact of CAR T therapy on HRQoL in patients with DLBCL throughout their treatment journey. Health care professionals and investigators can utilize these data in examining existing patient-reported outcome (PRO) measures that are used in DLBCL clinical trials and to better understand the needs of DLBCL survivors.

Uncontrolled chemotherapy-induced nausea and vomiting (CINV) can reduce patients’ quality of life and may result in premature discontinuation of chemotherapy. Although nausea and vomiting are commonly grouped together, research has shown that antiemetics are clinically effective against chemotherapy-induced vomiting (CIV) but less so against chemotherapy-induced nausea (CIN). Nausea remains a problem for up to 68% of patients who are prescribed guideline-consistent antiemetics. Despite the high prevalence of CIN, relatively little is known regarding its etiology independent of CIV. In this review paper, we summarize a metagenomics approach to the study and treatment of CIN with the goal of encouraging future research. Metagenomics focuses on genetic risk factors, encompassing both human (i.e., host) and gut microbial genetic variation. Little work to date has focused on metagenomics as a putative biological mechanism of CIN. Metagenomics has the potential to be a powerful tool in advancing scientific understanding of CIN by identifying new biological pathways and intervention targets. Investigation of metagenomics in the context of well-established demographic, clinical, and patient-reported risk factors may help to identify patients at risk and facilitate prevention and management of CIN.

PurposeOlder cancer survivors required medical care during the COVID-19 pandemic despite infection risks, but there are limited data on medical care in this age group. Methods. We evaluated care disruptions in a longitudinal cohort of non-metastatic breast cancer survivors ages 60-98 from five US regions (n=321). Survivors completed a web-based or telephone survey from May 27, 2020 to September 11, 2020. Care disruptions included self-reported interruptions in ability to see doctors, receive treatment or supportive therapies, or fill prescriptions. Logistic regression models evaluated bivariate and multivariate associations between care disruptions and education, medical, psychosocial and COVID-19-related factors. Multivariate models included age, county COVID-19 rates, comorbidity and post-diagnosis time. Results. There was a high response rate (n=262, 81.6%). Survivors were 32.2 months post-diagnosis (SD 17.5, range 4-73). Nearly half (48%) reported a medical disruption. The unadjusted odds of care disruptions were significantly higher with more education (OR 1.23 per one-year increase, 95% CI 1.09-1.39, p =0.001) and greater depression (OR 1.04 per one-point increase in CES-D score, CI 1.003-1.08, p=0.033); tangible support decreased the odds of disruptions (OR 0.99, 95% CI 0.97-0.99 per one-point increase, p=0.012). There was a trend for associations between disruptions and comorbidity (unadjusted OR 1.13 per 1 added comorbidity, 95% CI 0.99-1.29, p=0.07). Adjusting for covariates, only higher education (p=0.001) and tangible social support (p=0.006) remained significantly associated with having care disruptions. Conclusions. Older breast cancer survivors reported high rates of medical care disruptions during the COVID-19 pandemic and psychosocial factors were associated with care disruptions.

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 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.

Hematopoietic stem cell transplantation (HCT) is a potentially curative treatment for many hematologic conditions. Despite advances in conditioning and supportive measures, however, there remain significant comorbidities that threaten survivorship. Adverse effects of stress-related biobehavioral processes—defined here as the interactions of behavioral, psychological, and socioenvironmental factors with biology—impact immune recovery and function and are particularly salient in the HCT context, given the importance of immune reconstitution for improved survivorship. However, biobehavioral processes have been underinvestigated in this vulnerable group compared with other cancer populations. Here the Biobehavioral Research Special Interest Group (SIG) of the American Society for Transplantation and Cellular Therapy provides an expert review to inform research directions explicating the biological correlates of behavioral symptoms and evaluate the impact of these on HCT outcomes. The goal of this expert review is to provide a foundation for advancing science that effectively integrates behavioral and biological processes to optimize quality of life and improve clinical outcomes for HCT recipients.

Background Cyclin‐dependent kinase 4 and 6 (CDK4/6) inhibitor targeted therapies dramatically improve survival outcomes for metastatic breast cancer (MBC), but they are associated with significant symptom burden that can impact patients’ health‐related quality of life (HRQOL) and treatment outcomes. This study is the first to describe CDK4/6 inhibitor symptoms from the lived perspectives of MBC patients taking CDK4/6 inhibitors and healthcare providers involved in MBC care. This study also explored patients’ symptom management and HRQOL concerns, and gathered feedback about developing supportive interventions for MBC. Methods MBC patients taking CDK4/6 inhibitors (N = 20) and MBC healthcare providers (N = 12) participated in semi‐structured interviews that were analyzed for qualitative themes. MBC patients completed surveys about HRQOL, symptoms, and unmet needs. Results Patient and provider perceptions of CDK4/6 inhibitor symptoms did not align with patients perceiving symptoms as more burdensome. Patients reported that supportive resources (e.g., support groups, blogs) that are not specific to MBC do not adequately meet their needs. Patients and providers were enthusiastic about developing supportive interventions specifically for MBC and offered considerations for designing such interventions. Conclusions Findings highlight differences in perceptions of CDK4/6 inhibitor symptom burden between MBC patients and providers. Results will inform the development of supportive interventions to assist MBC patients in managing CDK4/6 inhibitor symptom burden and maintaining HRQOL. Such interventions could also improve treatment outcomes., Metastatic breast cancer (MBC) patient and provider perceptions of symptoms associated with CDK4/6 inhibitor did not align, with patients perceiving symptoms as more burdensome. Patients reported that supportive resources (e.g., support groups, blogs) that are not specific to MBC do not adequately meet their needs, however patients and providers were enthusiastic about developing supportive interventions specifically for MBC and offered considerations for designing such interventions. Results will inform the development of supportive interventions to assist MBC patients in managing CDK4/6 inhibitor symptom burden and maintaining health‐related quality of life.

Background The coronavirus disease 2019 (COVID‐19) pandemic has had wide‐ranging health effects and increased isolation. Older with cancer patients might be especially vulnerable to loneliness and poor mental health during the pandemic. Methods The authors included active participants enrolled in the longitudinal Thinking and Living With Cancer study of nonmetastatic breast cancer survivors aged 60 to 89 years (n = 262) and matched controls (n = 165) from 5 US regions. Participants completed questionnaires at parent study enrollment and then annually, including a web‐based or telephone COVID‐19 survey, between May 27 and September 11, 2020. Mixed‐effects models were used to examine changes in loneliness (a single item on the Center for Epidemiologic Studies–Depression [CES‐D] scale) from before to during the pandemic in survivors versus controls and to test survivor‐control differences in the associations between changes in loneliness and changes in mental health, including depression (CES‐D, excluding the loneliness item), anxiety (the State‐Trait Anxiety Inventory), and perceived stress (the Perceived Stress Scale). Models were adjusted for age, race, county COVID‐19 death rates, and time between assessments. Results Loneliness increased from before to during the pandemic (0.211; P = .001), with no survivor‐control differences. Increased loneliness was associated with worsening depression (3.958; P < .001) and anxiety (3.242; P < .001) symptoms and higher stress (1.172; P < .001) during the pandemic, also with no survivor‐control differences. Conclusions Cancer survivors reported changes in loneliness and mental health similar to those reported by women without cancer. However, both groups reported increased loneliness from before to during the pandemic that was related to worsening mental health, suggesting that screening for loneliness during medical care interactions will be important for identifying all older women at risk for adverse mental health effects of the pandemic., Older breast cancer survivors and matched noncancer controls experienced similar increases in loneliness from before to during the COVID‐19 pandemic. Women who reported increased loneliness also experienced worsening depression and anxiety symptoms and higher stress during the pandemic.

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

Background Systemic therapy (ST) can be deferred in patients who have metastatic renal cell carcinoma (mRCC) and slow-growing metastases. Currently, this subset of patients managed with active surveillance (AS) is not well described in the literature. Methods This was a prospective observational study of patients with mRCC across 46 US community and academic centers. The objective was to describe baseline characteristics and demographics of patients with mRCC initially managed by AS, reasons for AS, and patient outcomes. Descriptive statistics were used to characterize demographics, baseline characteristics, and patient-related outcomes. Wilcoxon 2-sample rank-sum tests and χ2 tests were used to assess differences between ST and AS cohorts in continuous and categorical variables, respectively. Kaplan-Meier survival curves were used to assess survival. Results Of 504 patients, mRCC was initially managed by AS (n = 143) or ST (n = 305); 56 patients were excluded from the analysis. Disease was present in 69% of patients who received AS, whereas the remaining 31% had no evidence of disease. At data cutoff, 72 of 143 patients (50%) in the AS cohort had not received ST. The median overall survival was not reached (95% CI, 122 months to not estimable) in patients who received AS versus 30 months (95% CI, 25-44 months) in those who received ST. Quality of life at baseline was significantly better in patients who were managed with AS versus ST. Conclusions AS occurs frequently (32%) in real-world clinical practice and appears to be a safe and appropriate alternative to immediate ST in selected patients.

Background We evaluated deficit accumulation and how deficits affected cognition and physical activity among breast cancer survivors and non-cancer controls. Methods Newly diagnosed nonmetastatic survivors (n = 353) and matched non-cancer controls (n = 355) ages 60-98 years without neurological impairments were assessed presystemic therapy (or at enrollment for controls) from August 2010 to December 2016 and followed for 36 months. Scores on a 42-item index were analyzed in growth-mixture models to determine deficit accumulation trajectories separately and combined for survivors and controls. Multilevel models tested associations between trajectory and cognition (FACT-Cog and neuropsychological tests) and physical activity (IPAQ-SF) for survivors and controls. Results Deficit accumulation scores were in the robust range, but survivors had higher scores (95% confidence intervals [CI]) than controls at 36 months (0.18, 95% CI = 0.16 to 0.19, vs 0.16, 95% CI = 0.14 to 0.17; P = .001), and averages included diverse deficit trajectories. Survivors who were robust but became frailer (8.8%) had similar baseline characteristics to those remaining robust (76.2%) but experienced a 9.6-point decline self-reported cognition (decline of 9.6 vs 3.2 points; P = .04) and a 769 MET minutes per week decline in physical activity (P < .001). Survivors who started and remained prefrail (15.0%) had self-reported and objective cognitive problems. At baseline, frail controls (9.5%) differed from robust controls (83.7%) on deficits and self-reported cognition (P < .001). Within combined trajectories, frail survivors had more sleep disturbances than frail controls (48.6% [SD = 17.4%] vs 25.0% [SD = 8.2%]; P = .05). Conclusions Most survivors and controls remained robust, and there were similar proportions on a frail trajectory. However, there were differences in deficit patterns between survivors and controls. Survivor deficit accumulation trajectory was associated with patient-reported outcomes. Additional research is needed to understand how breast cancer and its treatments affect deficit accumulation.

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

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

BACKGROUND: The internet can be a valuable tool in delivering survivorship care to hematopoietic cell transplantation (HCT) cancer survivors. We describe the reach of INSPIRE, an internet and social media-based randomized controlled trial, to address healthcare and psychosocial needs of HCT survivors. MATERIALS AND METHODS: All survivors 2–10 years after HCT for hematologic malignancy or myelodysplasia from six transplant centers in the US were approached by mail and follow-up calls. Eligible participants had access to the internet, an email address, and did not have active disease in the past two years. We used logistic regression to determine characteristics of eligible survivors who were more or less likely to enroll. RESULTS: Of 2578 eligible HCT survivors, 1065 (41%) enrolled in the study. Mean age of enrollees was 56.3 (SD=12.6; age range 19 to 89 years), 52% were male, and 94% were White. Survivors less likely to enroll included those who were male, age younger than 40, and who received an autologous transplant (all P

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.

Fear of cancer recurrence (FCR) is one of the most common and distressing issues affecting cancer survivors. This study examined (1) the association between modifiable cognitive, behavioral, and social characteristics and FCR, (2) the association between non-modifiable characteristics and FCR, and (3) the relative contributions of modifiable and non-modifiable characteristics to FCR. Participants (n = 120) had been diagnosed with colorectal cancer and completed cancer treatment in the past 6 to 36 months. Participants completed self-report measures of modifiable cognitive (e.g., beliefs about worry), behavioral (e.g., health-related reassurance seeking), and social (e.g., social constraints) characteristics. Non-modifiable characteristics (e.g., age, disease severity) were assessed via self-report and medical record review. Modifiable (i.e., perceived risk, self-efficacy, positive beliefs about worry, negative beliefs about worry, intolerance of uncertainty, rumination, reassurance seeking, health-related reassurance seeking, social constraints) and non-modifiable (i.e., age, gender, disease severity, neuroticism, conscientiousness) characteristics were associated with FCR (p’s

Patient-generated health data (PGHD), or health-related data gathered from patients to help address a health concern, are used increasingly in oncology to make regulatory decisions and evaluate quality of care. PGHD include self-reported health and treatment histories, patient-reported outcomes (PROs), and biometric sensor data. Advances in wireless technology, smartphones, and the Internet of Things have facilitated new ways to collect PGHD during clinic visits and in daily life. The goal of the current review was to provide an overview of the current clinical, regulatory, technological, and analytic landscape as it relates to PGHD in oncology research and care. The review begins with a rationale for PGHD as described by the US Food and Drug Administration, the Institute of Medicine, and other regulatory and scientific organizations. The evidence base for clinic-based and remote symptom monitoring using PGHD is described, with an emphasis on PROs. An overview is presented of current approaches to digital phenotyping or device-based, real-time assessment of biometric, behavioral, self-report, and performance data. Analytic opportunities regarding PGHD are envisioned in the context of big data and artificial intelligence in medicine. Finally, challenges and solutions for the integration of PGHD into clinical care are presented. The challenges include electronic medical record integration of PROs and biometric data, analysis of large and complex biometric data sets, and potential clinic workflow redesign. In addition, there is currently more limited evidence for the use of biometric data relative to PROs. Despite these challenges, the potential benefits of PGHD make them increasingly likely to be integrated into oncology research and clinical care.

Survivorship care for patients with prostate cancer requires careful consideration of unique disease-specific factors, including the prolonged natural disease history, the potential for competing health risks, and the consequences of long-term androgen deprivation therapy. However, current prostate cancer survivorship research is unfortunately limited by the lack of a robust supportive evidence base, variability in the definitions and measurement of survivorship outcomes, and a heavy reliance on expert opinion. As a result, the conduct of quality prostate cancer survivorship research is of increasing importance for patients, medical providers, and other key stakeholders. This manuscript harmonizes a path forward for improving prostate cancer survivorship by defining prostate cancer survivorship and survivorship research, as well as by highlighting key research priorities and cooperative mechanisms for survivorship studies within prostate cancer, with a particular focus on men with advanced disease.

Objective Cancer-associated cognitive decline is a concern among cancer survivors. Survivors' memory lapses (eg, location of keys, names, and reason entered room) may negatively impact quality of life. This study used smartphone-based surveys to compare cancer survivors to those without cancer history on frequency of, severity of, and affective response to daily memory lapses. Methods For 14 evenings, breast cancer survivors (N = 47, M age = 52.9) and women without a cancer history (N = 105, M age = 51.8) completed smartphone-based surveys on memory lapse occurrence and severity and negative and positive affect. Results Survivors were nearly three times more likely to report a daily memory lapse but did not differ from comparison group on memory lapse severity. Negative affect was significantly higher on days with memory lapses associated with doing something in the future (eg, appointments) but this did not differ across groups. Positive affect was not significantly related to survivorship status or the occurrence of daily memory lapses. Conclusion Survivors may be at-risk for more frequent memory lapses. Both survivors and women without a history of cancer reported greater negative affect on days when memory lapses occurred, suggesting that daily cognitive functioning may have important implications for quality of life.

Despite high levels of stress, there are few empirically supported stress management interventions for caregivers of allogeneic hematopoietic stem cell transplant (HCT) cancer patients. This study examined the feasibility, acceptability, and various stress-related outcomes from pre- to post-treatment of a pilot, single-arm trial of a 6-week mindfulness-based intervention (FOCUS) for stress management. Caregivers (N = 21; 76% female; mean age = 57.43) were enrolled prior to patient transplant and received FOCUS during the first 90 days post-transplant. Findings indicated that FOCUS was highly feasible and acceptable (e.g., 71% attended at least four of six sessions; 100% reported using the skills learned at follow-up; high treatment engagement). Significant increases in mindfulness, post-traumatic growth, and general mental health were observed, along with significant decreases in negative affect (all ps < .05).

PURPOSE: Cancer has long-term financial consequences. Adolescent and young adult (AYA) and middle-aged cancer survivors may experience more financial toxicity than older adults. This study examined age differences in financial distress in hematopoietic cell transplant survivors and whether these differences result from measurement bias, more financial barriers to care or an overall higher level of distress. METHODS: Hematologic malignancy survivors (n=1,135, 2–10 years post-transplant) completed the Cancer and Treatment Distress scale (CTXD) and demographics as part of the baseline assessment for a randomized clinical trial. The CTXD has seven subscales but for this study we examined the financial distress subscale and the overall score. Item response theory analyses tested for bias by age and gender. Multivariate linear regression tested the association of age and gender with the CTXD scores while controlling for financial barriers to care. RESULTS: No bias was found on the CTXD. AYA (p0.18). Financial barriers to care were not associated with financial or overall distress. CONCLUSIONS: Part of the increase in financial distress with younger age may be due to a higher risk of general distress. Policy initiatives to control cancer costs should consider life stage and the unique financial challenges at different ages for men and women.

We conducted a prospective study of adult allogeneic hematopoietic cell transplantation (HCT) recipients to assess pre- and post-HCT physical function. Baseline measurements included a wrist actigraphy, a 6 min walk test (6MWT), an international physical activity questionnaire (IPAQ), and a Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) as well as serial post-HCT assessments of 6MWT, IPAQ, and FACT-BMT. Forty-seven patients were evaluable for functionality assessments, with a median follow-up of 54.5 months for surviving recipients. No patients demonstrated vigorous or very vigorous activity at any time during monitoring by wrist actigraphy; patients spent a median of 6 h daily sedentary. Self-reported activity via the IPAQ showed 36%, 43%, and 21% of subjects reporting light, moderate, and vigorous activity prior to HCT, respectively. Post-HCT 6MWTs on day +30 demonstrated the greatest association with subsequent survival and non-relapse mortality. A decline in 6MWT distance over time also demonstrated worsened overall survival. This study shows the feasibility of fitness assessments and the ability to risk stratify for subsequent mortality, particularly using the 6MWT on the day +30 single time point assessment and change scores from baseline to day +30 post HCT. These pilot findings suggest important targets for future study.

This cross-sectional study assesses data from the 2017-2020 Health Information National Trends Survey to examine whether smartphone-only internet access is associated with patient portal use.

Racial and ethnic disparities are well-documented in cancer outcomes such as disease progression and survival, but less is known regarding potential disparities in symptom burden.The goal of this retrospective study was to examine differences in symptom burden by race and ethnicity in a large sample of cancer patients. We hypothesized that racial and ethnic minority patients would report greater symptom burden than non-Hispanic and White patients.A total of 5798 cancer patients completed the Edmonton Symptom Assessment Scale-revised (ESAS-r-CSS) at least once as part of clinical care. Two indicators of symptom burden were evaluated: (1) total ESAS-r-CSS score (i.e., overall symptom burden) and (2) number of severe symptoms (i.e., severe symptomatology). For patients completing the ESAS-r-CSS on multiple occasions, the highest score for each indicator was used. Zero-inflated negative binomial regression analyses were conducted, adjusting for other sociodemographic and clinical characteristics. Symptomology varied across race. Patients who self-identified as Black reported higher symptom burden (p = .016) and were more likely to report severe symptoms (p .001) than self-identified White patients. Patients with "other" race were also more likely to report severe symptoms than White patients (p = .032), but reported similar total symptom burden (p = .315). Asian and Hispanic patients did not differ from White or non-Hispanic patients on symptom burden (ps .05).This study describes racial disparities in patient-reported symptom burden during routine oncology care, primarily observed in Black patients. Clinic-based electronic symptom monitoring may be useful to detect high symptom burden, particularly in patients who self-identify their race as Black or other. Future research is needed to reduce symptom burden in racially diverse cancer populations.

BACKGROUND Sleep disturbance and genetic profile are risks for cognitive decline in noncancer populations, yet their role in cancer-related cognitive problems remains understudied. This study examined whether sleep disturbance was associated with worse neurocognitive outcomes in breast cancer survivors and whether sleep effects on cognition varied by genotype. METHODS Newly diagnosed female patients (n = 319) who were 60 years old or older and had stage 0 to III breast cancer were recruited from August 2010 to December 2015. Assessments were performed before systemic therapy and 12 and 24 months later. Neuropsychological testing measured attention, processing speed, executive function, learning, and memory; self-perceived cognitive functioning was also assessed. Sleep disturbance was defined by self-report of routine poor or restless sleep. Genotyping included APOE, BDNF, and COMT polymorphisms. Random effects fluctuation models tested associations of between-person and within-person differences in sleep, genotype, and sleep-genotype interactions and cognition and controlled for age, reading level, race, site, and treatment. RESULTS One-third of the patients reported sleep disturbances at each time point. There was a sleep-APOE e4 interaction (P = .001) in which patients with the APOE e4 allele and sleep disturbances had significantly lower learning and memory scores than those who were APOE e4-negative and without sleep disturbances. There was also a sleep disturbance-COMT genotype interaction (P = .02) in which COMT Val carriers with sleep disturbances had lower perceived cognition than noncarriers. CONCLUSIONS Sleep disturbance was common and was associated with worse cognitive performance in older breast cancer survivors, especially those with a genetic risk for cognitive decline. Survivorship care should include sleep assessments and interventions to address sleep problems.

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

BACKGROUND: Hematopoietic cell transplant (HCT) can cause significant distress in patients and their informal caregivers. Despite advances in reduced intensity conditioning and supportive care, few recent studies have reported rates of clinically-significant post-traumatic stress disorder symptomatology (hereafter referred to as PTSD). Goals of the current study were to: 1) examine rates of PTSD and distress in patients and caregivers and 2) identify sociodemographic and clinical risk factors for PTSD. METHODS: As part of an annual survivorship survey, 2,157 HCT recipients and their caregivers were mailed self-report measures of PTSD and distress. Patients also completed self-report measures of sociodemographic information (e.g., age, sex, employment status). Clinical variables (e.g., time since transplant, transplant type) were captured in the transplant database. RESULTS: A total of 691 recipients (56% age 60 or above at the time of survey, 47% female, median 10.1 years post-HCT) and 333 caregivers provided PTSD data and were included in the current analyses. More caregivers reported PTSD (6.6%) than patients (3.3%) (p=0.02). Patients or caregivers who had PTSD reported significantly higher distress related to uncertainty, family strain, medical demands, finances, identity, and health burden (p values < 0.0001) compared to those without PTSD. Patient but not caregiver PTSD was associated with more recent transplant (p=0.01, p=0.16). CONCLUSIONS: Rates of PTSD are relatively low in long-term survivors of HCT and their caregivers. Nevertheless, results are consistent with other studies of cancer caregiving suggesting that caregivers often experience greater distress than patients. Timely referral to psychosocial services should be offered to both HCT recipients and caregivers reporting symptoms of PTSD.

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 (β = − 0.33, p = 0.009) and more disturbed sleep (β = − 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

Background: Physical function prior to allogeneic hematopoietic cell transplant (HCT) is associated with survival and may be associated with patient physical activity (PA). Tools to evaluate PA prior to HCT are scarce. We aimed to evaluate the impact of easily obtained patient-report of PA prior to HCT on survival. Methods: HCT recipients between January 1, 2011 and July 5, 2018 and who completed an International Physical Activity Questionnaire Short Form were included. This patient survey captures self-reported activities over the preceding week to determine PA level. Results: We report a retrospective study of 587 adult (age ≥18) HCT recipients. The median age for the cohort was 57.9 years (range 19.9–76.1) with 149 patients (25.4%) age ≥65. Younger patients reported higher PA (low, median age 59.7 years; moderate, 56.1; high, 55.7; p < 0.001). High activity level was reported by males (66.7%; p < 0.001). Patients with low PA had HCT-comorbidity index (HCT-CI) ≥ 3 (68.1%, p = 0.002). When controlling for HCT-CI and disease risk index, higher PA was associated with improved overall survival (HR 0.954, 95% CI 0.921–0.988, p = 0.009). After adjusting for HCT-CI, higher PA was associated with reduced non-relapse mortality (NRM) (HR 0.931, 95% CI 0.891–0.972, p = 0.0013). Subgroup analysis in adults age ≥65 years also found that PA was lower in this population and associated with NRM mortality (HR 0.95, 95% CI 0.90–0.99, p = 0.041). Conclusion: Patient-reported PA is a predictor of post-HCT survival. Future studies to validate incorporation of self-report tools to better predict patient-related adverse risk are warranted.

Introduction : The Metastatic Renal Cell Carcinoma (MaRCC) Registry provides prospective data on real-world treatment patterns and outcomes in patients with metastatic renal cell carcinoma (mRCC). Methods and Materials : Patients with mRCC and no prior systemic therapy were enrolled at academic and community sites. End of study data collection was in March 2019. Outcomes included overall survival (OS). A survey of treating physicians assessed reasons for treatment initiations and discontinuations. Results : Overall, 376 patients with mRCC initiated first-line therapy; 171 (45.5%) received pazopanib, 75 (19.9%) sunitinib, and 74 (19.7%) participated in a clinical trial. Median (95% confidence interval) OS was longest in the clinical trial group (50.3 [35.8–not reached] months) versus pazopanib (39.0 [29.7–50.9] months) and sunitinib 26.2 [19.9–61.5] months). Non-clear cell RCC (21.5% of patients) was associated with worse median OS than clear cell RCC (18.0 vs 47.3 months). Differences in baseline characteristics, treatment starting dose, and relative dose exposure among treatment groups suggest selection bias. Survey results revealed a de-emphasis on quality of life, toxicity, and patient preference compared with efficacy in treatment selection. Conclusion : The MaRCC Registry gives insights into real-world first-line treatment selection, outcomes, and physician rationale regarding initial treatment selection prior to the immunotherapy era. Differences in outcomes between clinical trial and off-study patients reflect the difficulty in translating trial results to real-world patients, and emphasize the need to broaden clinical trial eligibility. Physician emphasis on efficacy over quality of life and toxicity suggests more data and education are needed regarding these endpoints. MicroAbstract : The Metastatic Renal Cell Carcinoma Registry provides prospective data on real-world treatment patterns and outcomes in patients with metastatic renal cell carcinoma (mRCC). 376 patients with mRCC and no prior systemic therapy were included in this study. This report describes initial real-world treatment patterns. Physician emphasis on efficacy over quality of life and toxicity suggests more data and education are needed.

Background Cancer-related cognitive decline (CRCD) has been linked to apolipoprotein E (APOE) gene ε4 polymorphisms. APOE ε4 polymorphisms are also the strongest genetic risk for late-onset Alzheimer disease (AD), whereas ε2 polymorphisms protect against AD. However, the effects of ε2 polymorphisms on CRCD have not been evaluated. Methods We evaluated nonmetastatic breast cancer survivors (n = 427) and matched noncancer controls (n = 407) ages 60-98 years assessed presystemic therapy from August 2010 to December 2017 with annual follow-up to 24 months. Neuropsychological assessment measured attention, processing speed, executive function, and learning and memory. Linear mixed-effects models tested the effects of having an ε2 allele (vs none) on longitudinal cognitive domain z scores by treatment group (chemotherapy with or without hormonal therapy, hormonal therapy, and control) controlling for covariates; participants with ε2/ε4 genotype were excluded. Sensitivity analyses examined effects of other covariates and any ε4 positivity. Results There was an interaction with genotype for attention, processing speed, and executive functioning domain scores (Beta = 0.32, 95% confidence interval = 0.00 to 0.65); the chemotherapy group with an ε2 allele had higher scores at baseline and maintained higher scores over time compared with those without an ε2 allele, and this protective effect was not seen for other groups. There was no effect of ε2 on learning and memory domain scores. Conclusions APOE ε2 polymorphisms may protect against CRCD in older breast cancer survivors receiving chemotherapy. With replication, this information could be useful for survivorship care and informing future studies of possible links to AD and defining mechanisms of protection.

Simple Summary Although people with metastatic cancer are living longer with their disease, they are faced with challenges that can interfere with their quality of life. These challenges include worsening disease, survival time, symptoms, distress, and financial problems. The aim of this review paper is to describe a framework to guide future efforts to address these challenges. The framework includes the risk factors (predisposing factors), triggers (precipitating factors), and responses (perpetuating factors) that contribute to the onset and maintenance of problems in living with metastatic cancer. We conclude by suggesting areas for future work to prevent problems, manage triggers, and reduce unhelpful responses. Abstract Living with metastatic cancer, or metavivorship, differs from cancer survivorship and has changed as novel treatments have increased survival time. The purpose of this narrative review is to describe factors that impact challenges in metavivorship within a conceptual framework to guide future research. This review focuses on the specific metavivorship outcomes of progressive disease, survival time, symptoms, distress, financial toxicity, and quality of life. We describe the predisposing, precipitating, and perpetuating (3P) model of metavivorship. Understanding the biological, psychological, and social 3P factors that contribute to the development and maintenance of challenges in metavivorship provides a roadmap for future research. Implications of this model include prevention by targeting predisposing factors, management of precipitating factors after onset of metastatic disease, and treatment of perpetuating factors to reduce symptoms and improve quality of life during the chronic phase of metavivorship. This can be accomplished through biopsychosocial screening efforts, monitoring of patient-reported outcomes, education and communication interventions, interdisciplinary symptom management, advance care planning, and behavioral interventions to cultivate psychological resilience.

HIGHLIGHTS • Distances from transplant (HCT) centers exceed 100 miles for 44% of survivors • We examined driving distances, distress, & physical function among HCT survivors • Chronic GVHD and low income predicted worsened distress & function • Interestingly, lack of Internet access also predicted worsened distress & function • Surprisingly, driving distance had no impact on distress or physical function, Long driving distances to transplantation centers may impede access to care for hematopoietic cell transplantation (HCT) survivors. As a secondary analysis from the multicenter INSPIRE study (NCT01602211), we examined baseline data from relapse-free HCT adult survivors (2-10 years after allogeneic or autologous HCT) to investigate the association between driving distances and patient-reported outcome (PRO) measures of distress and physical function. We analyzed predictors of elevated distress and impaired physical function using logistic regression models that operationalized driving distance first as a continuous variable and separately as a dichotomous variable (

Objective To investigate the relationships between self-reported and objectively measured cognitive function prior to systemic therapy and subsequent well-being outcomes over 24 months in older breast cancer survivors. Methods Data were from 397 women aged 60 to 98 diagnosed with non-metastatic breast cancer in the Thinking and Living with Cancer Study recruited from 2010-2016. Cognitive function was measured at baseline (following surgery, prior to systemic therapy) using neuropsychological assessments of attention, processing speed, and executive function (APE), learning and memory (LM), and the self-reported FACT-Cog scale. Well-being was measured using the FACT-G functional, physical, social, and emotional well-being domain scales at baseline and 12 and 24 months later, scaled from 0 (low) to 100 (high). Linear mixed-effects models assessed the relationships between each of baseline APE, LM, and FACT-Cog quartiles with well-being scores over 24 months, adjusted for confounding variables. Results At baseline, older survivors in the lowest APE, LM, and FACT-Cog score quartiles experienced poorer global well-being than those in the highest quartiles. At 24 months, older survivors tended to improve in well-being, and there were no differences according to baseline APE or LM scores. At 24 months, mean global well-being was 80.3 (95% CI: 76.2-84.3) among those in the lowest vs 86.6 (95% CI: 83.1-90.1) in the highest FACT-cog quartile, a clinically meaningful difference of 6.3 points (95% CI: 1.5-11.1). Conclusions Among older breast cancer survivors, self-reported, but not objective cognitive impairments, were associated with lower global well-being over the first 2 years of survivorship.

Aim: To develop a comprehensive item library of patient-reported, immunotherapy-related adverse events (irAEs) that draws from and expands on the Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System. Methods: Literature review and iterative expert input. Based on a literature review of irAEs, we developed a framework of immunotherapy classes and their associated symptoms. Clinical experts then reviewed iterations of symptom summaries and item maps linked to the immunotherapy framework. Experts provided content review and feedback was shared across experts until consensus was reached. The iterative process facilitated creation of a Primary Symptom List associated with immune checkpoint modulators (ICMs), drawn from the larger set of symptoms. Existing FACIT items were mapped to the symptom list, and new items were written as needed to create the item library. Results: The full item library of irAEs is comprised of 239 items, covering 142 unique symptoms across 75 inflammatory reactions/immune conditions. A subset of 66 items comprises a Primary Symptom List considered most common/relevant to ICM treatment. This includes gastrointestinal, skin, pulmonary, neurologic, musculoskeletal, and multiple miscellaneous and constitutional symptoms. Conclusion: The FACIT Immunotherapy Item Library is a compilation of 239 self-report items that capture the wide range of AEs experienced by people receiving immune treatments. A subset of 66 items comprises a Primary Symptom List meant for ICM therapy. Use of items selected from this library is encouraged in clinical research and clinical practice evaluation.

Informal caregivers of allogeneic hematopoietic cell transplant patients experience significant levels of stress throughout the caregiving process. One strategy that has been shown to aid in stress management in other populations is mindfulness. The goal of this study was to understand caregivers' experiences with mindfulness and evaluate their receptiveness to a mindfulness-based stress management program. Data were collected via in-depth phone interviews from 18 caregivers (55% female). Results indicated that about half the sample was familiar with mindfulness and/or had practiced meditation. The majority indicated that they believed a mindfulness program would have been useful for them and that they would have been willing to participate. Most indicated that a program delivered once-weekly for 60 min, during both inpatient and outpatient phases, would be preferable through a combination of in-person and mobile-based delivery. These data provide critical information for the development of future mindfulness-based interventions for this caregiving population.

Treatment-related fatigue significantly limits quality of life among chronic myeloid leukemia (CML) patients receiving tyrosine kinase inhibitors (TKIs), yet no interventions to reduce this symptom have been studied. We examined preliminary feasibility and efficacy of cognitive behavioral therapy for TKI treatment-related fatigue in patients with CML. We used a mixed methods convergent design and collected quantitative data through randomized single-case experiments. We included CML patients receiving TKIs and reporting severe fatigue. Within each participant, we compared CBT to a no-treatment baseline period. Fatigue severity was measured weekly with the Checklist Individual Strength. Fatigue scores were subjected to visual analyses and randomization tests for single-case experimental designs. We conducted qualitative interviews after study participation and focused on feasibility and efficacy of CBT. Visual inspection of line graphs indicated downward trends in the expected direction for fatigue in two of the four participants. The test statistics showed a decrease in fatigue severity for all participants but randomization tests did not reach statistical significance (overall p = 0.18). Participants reported qualitative improvements in level of functioning and coping with fatigue. CBT was considered feasible and acceptable for severely fatigued CML patients. Our study provided preliminary evidence for the feasibility and acceptability of CBT for severely fatigued CML patients receiving targeted therapy. We recommend further efficacy testing of this promising intervention in a pilot randomized controlled trial. ispartof: Journal of Clinical Psychology in Medical Settings vol:26 issue:4 pages:440-448 ispartof: location:United States status: published

Chronic graft-versus-host disease occurs in 20–50% of allogeneic hematopoietic cell transplant survivors. We surveyed patients about their quality of life, symptoms, health status, comorbid conditions and medications. Instruments included the Short-Form-36 (SF-36), the Patient-Reported Outcomes Measurement Information System (PROMIS) Global and PROMIS-29 scales and the Lee Chronic Graft-versus-Host Disease Symptom Scale. Functional status was measured by self-reported Karnofsky performance status and work status. Of 3027 surveys sent to recipients surviving one or more years after transplantation, 1377 (45%) were returned. Among these, patients reported that their chronic graft-versus-host disease was mild (n=257, 18.7%), moderate (n=110, 8.0%) or severe (n=25, 1.8%). Another 377 (27.4%) had never had chronic graft-versus-host disease and 280 (20.3%) had had chronic graft-versus-host disease but it had resolved. We excluded 328 (23.8%) patients who did not answer the questions about chronic graft-versus-host disease. Patients who reported moderate or severe chronic graft-versus-host disease reported worse quality of life, lower performance status, a higher symptom burden and were more likely to be taking prescription medications for pain, anxiety and depression compared to those with resolved chronic graft-versus-host disease. Self-reported measures were similar between patients with resolved chronic graft-versus-host disease and those who had never had it. Our data suggest that the PROMIS measures may be able to replace the SF-36 in the assessment of chronic graft-versus-host disease. Between 26.7–39.4% of people with active chronic graft-versus-host disease were unable to work due to health reasons, compared with 12.1% whose chronic graft-versus-host disease had resolved and 15.4% who had never had chronic graft-versus-host disease. Mouth, eye and nutritional symptoms persisted after resolution of chronic graft-versus-host disease. These results show that better prevention of and treatment for chronic graft-versus-host disease are needed to improve survivorship after allogeneic transplantation.

OBJECTIVE: To evaluate how use of different reference populations affects estimates of breast cancer-related cognitive impairment rates. METHODS: Patients aged ≥60 years with stage 0–3 breast cancer (n = 371) and matched non-cancer controls (n = 370) completed 13 neuropsychological tests prior to systemic therapy or at enrollment (controls). The tests captured three domains: attention, processing speed and executive function; learning and memory; and visual-spatial function. Domain-specific impairment was defined as having one test score 2 SD below or two or more test scores 1.5 SD below the reference population means. Different reference populations were used to define impairment: published normative data, study-specific controls, age and education-stratified controls, and age and education-adjusted controls. The associations between the resultant impairment rates and breast cancer (vs. control) were evaluated using chi-square tests and logistic regression models. Cohen’s kappa coefficients were used to evaluate agreement of impairment rates between study-specific control performance and the other reference population groups. RESULTS: The patients and controls were aged 68.0 (SD 6.0) and 67.9 (SD 7.0) years, respectively. The association of breast cancer-control status with impairment did not differ based on reference group. Cognitive impairment based on published normative data yielded less agreement on impairment rates (κ = 0.22–0.89) than study-specific age and education-stratified control performance (κ = 0.62–1.00). CONCLUSION: The choice of reference populations did not affect conclusions about the association of cognition with breast cancer. However, while study-specific reference populations provided greater internal consistency in defining cognitive impairment, benchmarking against published normative data will enhance the ability to compare results across studies.

Despite a high prevalence of sleep disruption among hematopoietic cell transplant (HCT) recipients, relatively little research has investigated its relationships with modifiable cognitive or behavioral factors or used actigraphy to characterize sleep disruption in this population. Autologous HCT recipients who were 6–18 months post transplant completed self-report measures of cancer-related distress, fear of cancer recurrence, dysfunctional sleep cognitions, and inhibitory sleep behaviors upon enrollment. Patients then wore an actigraph for 7 days and completed a self-report measure of sleep disruption on day 7 of the study. Among the 84 participants (age M = 60, 45% female), 41% reported clinically relevant sleep disruption. Examination of actigraph data confirmed that, on average, sleep was disrupted (wake after sleep onset M = 66 min) and sleep efficiency was less than recommended (sleep efficiency M = 78%). Cancer-related distress, fear of recurrence, dysfunctional sleep cognitions, and inhibitory sleep behaviors were related to self-reported sleep disruption (p values

T-helper 1 and T-helper 17 lymphocytes mediate acute graft-versus-host disease (GvHD). Interleukin 12 is critical for T-helper 1 differentiation and interleukin 23 for T-helper 17 maintenance. Interleukin 12 and 23 are heterodimeric cytokines that share the p40 subunit (IL-12/IL-23p40). In a randomized, blinded, placebo-controlled trial, we examined the biological impact and clinical outcomes following IL-12/IL-23p40 neutralization using ustekinumab. Thirty patients received peripheral blood mobilized hematopoietic cell transplantation (HCT) from HLA-matched sibling or unrelated donors, received sirolimus plus tacrolimus as GvHD prophylaxis, and were randomized to ustekinumab versus placebo with 1:1 allocation after stratification by donor type. The primary end point of the trial was the mean percentage (%) T-regulatory (Treg) cells on day 30 post HCT. Ustekinumab was delivered by subcutaneous injection on day −1 and day +20 after transplantation. On day 30 post transplant, no significant difference in % Treg was observed. Ustekinumab suppressed serum IL-12/IL-23p40 levels. Host-reactive donor alloresponse at days 30 and 90 after transplantation was polarized with significant reduction in IL-17 and IFN-α production and increase in IL-4. No toxicity attributed to ustekinumab was observed. Overall survival and National Institute of Health moderate/severe chronic GvHD-free, relapse-free survival were significantly improved among ustekinumab-treated patients. No significant improvements were observed in acute or chronic GvHD, relapse, or non-relapse mortality. These data provide first evidence that IL-12/IL-23p40 neutralization can polarize donor anti-host alloresponse in vivo and provide initial clinical efficacy evidence to be tested in subsequent trials. (Trial registered at clinicaltrials.gov identifier: 01713400.)

Introduction: 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) occurs in up to 64% of patients. There is concern that ICANS places patients at risk for longer-term cognitive impairment. This study examined changes in patients' perceived cognition from prior to CAR T-cell therapy to days 90 and 360 in patients diagnosed with non-Hodgkins lymphoma, as well as CAR T-cell therapy-specific risk factors (e.g., ICANS, cytokine release syndrome [CRS]) and non-specific risk factors (e.g., age, education) associated with changes in cognition. Methods: Patients' perceived cognition was assessed at baseline and at days 90 and 360 with the Everyday Cognition Questionnaire (ECog), that provides scores for global cognition (which includes subscales for memory, language, visuospatial abilities, planning, organization, divided attention), and satisfaction with cognition. Quality of life was scored using the Patient-Reported Outcomes Measurement Information System-29. Frailty was examined with the hand grip strength test. Cognitive reserve was examined with the Weschler Test of Adult Reading. Clinical variables were extracted from medical records. Demographic variables were self-reported by participants. Percentages of patients reporting clinically significant worsening, clinically significant improvement, and unchanged cognition over time were calculated. Piecewise mixed models were used to examine average change in perceived cognition from baseline to day 90 and from day 90 to day 360, as well as to explore potential risk factors of average change in global cognition. Risk factors included demographic (i.e., age, education) and clinical factors (i.e., grade>2 CRS, grade>2 ICANS, disease response at days 90 and 360, baseline grip strength, baseline cognitive reserve) as well as baseline quality of life variables (i.e., fatigue, physical function, pain, depression, anxiety). Results: A total of 118 participants provided data (mean age 61, 59% male, 86% diagnosed with large B-cell lymphomas, 87% received axicabtagene ciloleucel). At day 90, relative to baseline, 17% of participants reported worsened global cognition, 10% improved global cognition, and 73% no change in global cognition (Figure 1). At day 360, relative to baseline, 28% reported worsened global cognition, 11% improved global cognition, and 61% no change in global cognition (Figure 1). Piecewise mixed models indicated that from baseline to day 90, there were no changes on average in global cognition or in any cognitive domain (ps>.05). In contrast, from day 90 to 360, participants reported, on average, worsened global cognition (p=.01), language (p=.04), visuospatial abilities (p=.04), divided attention (p=.03) and satisfaction with cognition (p=.01). At baseline, greater fatigue, anxiety and depression were associated with worse concurrent perceived cognition (p.05). Post-hoc analyses indicated no differences in cognition by disease status at day 360 (ps>.05). Conclusions: Results suggest that perceived cognition worsens on average beyond day 90, with patients reporting worse baseline physical functioning being at risk of worse perceived cognition by day 90. Results should be incorporated when preparing patients about what to expect when receiving CAR T-cell therapy. Further research is needed regarding objective neurocognitive performance after CAR T-cell therapy. Figure 1 Figure 1. Disclosures Barata: Grifols: Current holder of individual stocks in a privately-held company; Almirall: Current holder of individual stocks in a privately-held company. Gonzalez: SureMed Compliance Equity: Consultancy; Elly Health, Inc.: Consultancy. Kirtane: Oncternal Therapeutics: Current holder of individual stocks in a privately-held company; Seattle Genetics: Current holder of individual stocks in a privately-held company; Myovant Sciences: Current holder of individual stocks in a privately-held company; Veru: Current holder of individual stocks in a privately-held company. Jain: Kite/Gilead: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; BMS/Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Mokhtari: Kite: Consultancy. Chavez: ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Speakers Bureau; AstraZeneca: Research Funding; Merck: Research Funding; Novartis: Consultancy; Epizyme: Speakers Bureau; BeiGene: Speakers Bureau; Kite/Gilead: Consultancy; Adaptive: Research Funding; Karyopharm Therapeutics: Consultancy; MorphoSys: Speakers Bureau; Abbvie: Consultancy. Lazaryan: Kadmon: Consultancy; Avrobio: Membership on an entity's Board of Directors or advisory committees; Humanigen: Membership on an entity's Board of Directors or advisory committees. Shah: Novartis: Consultancy, Other: Expenses; Pfizer: Consultancy, Other: Expenses; Amgen: Consultancy; Precision Biosciences: Consultancy; Kite, a Gilead Company: Consultancy, Honoraria, Other: Expenses, Research Funding; Pharmacyclics/Janssen: Honoraria, Other: Expenses; Acrotech/Spectrum: Honoraria; BeiGene: Consultancy, Honoraria; Incyte: Research Funding; Jazz Pharmaceuticals: Research Funding; Servier Genetics: Other; Bristol-Myers Squibb/Celgene: Consultancy, Other: Expenses; Adaptive Biotechnologies: Consultancy. Locke: Gerson Lehrman Group: Consultancy; Emerging Therapy Solutions: Consultancy; EcoR1: Consultancy; Cowen: Consultancy; Umoja: Consultancy, Other; Wugen: Consultancy, Other; Takeda: Consultancy, Other; Novartis: Consultancy, Other, Research Funding; Legend Biotech: Consultancy, Other; Janssen: Consultancy, Other: Scientific Advisory Role; Kite, a Gilead Company: Consultancy, Other: Scientific Advisory Role, Research Funding; Iovance Biotherapeutics: Consultancy, Other: Scientific Advisory Role; GammaDelta Therapeutics: Consultancy, Other: Scientific Advisory Role; Cellular Biomedicine Group: Consultancy, Other: Scientific Advisory Role; Calibr: Consultancy, Other: Scientific Advisory Role; BMS/Celgene: Consultancy, Other: Scientific Advisory Role; Bluebird Bio: Consultancy, Other: Scientific Advisory Role; Amgen: Consultancy, Other: Scientific Advisory Role; Allogene Therapeutics: Consultancy, Other: Scientific Advisory Role, Research Funding; Moffitt Cancer Center: Patents & Royalties: field of cellular immunotherapy. Jim: Kite pharma: Research Funding; Merck: Consultancy; Janssen Scientific Affairs: Consultancy; RedHill Biopharma: Consultancy.

Background: Hematopoietic cell transplantation (HCT) survivors have a complex and multiphase recovery period. Health care delivery and psychosocial interventions for HCT survivors are challenging as many HCT recipients live great distances from the facility where they had their HCT. Therefore, identifying factors associated with a patient's capability to self-manage symptoms is an important focus of survivorship research. A patient's self-efficacy may be important for the successful management of major stressors associated with treatments and recovery. Here, we aimed to evaluate the impact of perceived self-efficacy on distress, quality of life (QoL), depression, and fatigue, and identify the factors associated with lower self-efficacy. Methods: This cross-sectional study analyzed baseline data from a randomized controlled internet based self-management intervention trial (INSPIRE, NCT01602211) in adult (age 18 and older) survivors 2-10 years post HCT. Patients with recurrence or subsequent malignancy requiring cancer treatment during the two years prior to enrollment, inability to read and understand English and lack of access to email and the Internet were excluded. Data included medical records and patient-reported outcomes (PROs) including Cancer and Treatment Distress (CTXD) with 6 subscales, Patient Health Questionnaire depression scale (PHQ-8), Short Form 12 Health Survey (SF-12) physical function (PCS) and mental function (MCS) scores, Brief Fatigue Inventory (BFI) and Health Self-Efficacy. Pearson correlations were used to test bivariate associations for self-efficacy with CTXD, SF-12, BFI, and PHQ8. General linear models were used to test the independent association for CTXD and SF-12 outcomes with self-efficacy, controlling for selected sociodemographic and treatment covariates. Tenability of statistical model assumptions were examined, and no remediation was necessary. Results: Total of 1078 HCT survivors were included in the analysis. Participants were 18 to 76 years (mean age 51), 53% male, and over 90% white and non-Hispanic. Only 16% reported living in a rural area. A majority received an autologous HCT (55%) and were less than 5 years from their first HCT (54%). Among the allogeneic HCT recipients, more than half (60%) had active chronic Graft-versus-Host (cGVHD) and nearly 40% were on active systemic treatment. The mean self-efficacy score was 3.01 (SD 0.49). Female gender (p=0.014), younger age at HCT, younger age at cGVHD presentation, moderate to severe currently active cGVHD (p=0.003) and household income less than $40,000 (p < 0.001) were associated with lower self-efficacy. In bivariate analyses, self-efficacy was negatively correlated with mean total CTXD (r -0.5, p In a regression model investigating the impact of self-efficacy on CTXD controlled for demographics and disease characteristics , lower self-efficacy was independently associated with higher CTXD (beta -0.232; 95% CI (-0.294, -0.169), p< 0.001) (Table 1). Moreover, there was a significant positive relationship between self-efficacy and both mental (beta 4.68; 95% CI (3.82, 5.54); p Conclusion: Our study demonstrates that lower levels of self-efficacy reported by HCT survivors was independently associated with higher levels of symptoms such as fatigue and depression, lower QoL, and more cancer -related distress. Furthermore, self-efficacy is more likely to be impaired in females, younger adults, those with lower incomes, and survivors with active cGVHD. These findings support the value of self-management interventions focused on improving self-efficacy as having the potential to improve multiple symptoms and QoL in HCT survivors. Figure 1 Figure 1. Disclosures Farhadfar: Incyte: Consultancy. Jim: RedHill Biopharma: Consultancy; Janssen Scientific Affairs: Consultancy; Merck: Consultancy; Kite pharma: Research Funding. Majhail: Anthem, Inc: Consultancy; Incyte Corporation: Consultancy. Wingard: Merck: Consultancy; AlloVir: Consultancy; Celgene: Consultancy; Shire: Consultancy; Janssen: Consultancy; Cidara Therapeutics: Consultancy.