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Oxana Palesh,1 Luke Peppone,2 Pasquale F Innominato,3–5 Michelle Janelsins,2 Monica Jeong,1 Lisa Sprod,7 Josee Savard,6 Max Rotatori,1 Shelli Kesler,1 Melinda Telli,1 Karen Mustian21Stanford University School of Medicine, Stanford, CA, USA; 2University of Rochester School of Medicine and Dentistry, Rochester, NY, USA; 3INSERM, UMRS 776, Biological Rhythms and Cancers, Villejuif, France; 4Faculty of Medicine, Universite Paris Sud, le Kremlin-Bicêtre, France; 5APHP, Chronotherapy Unit, Department of Oncology, Paul Brousse Hospital, Villejuif, France; 6Laval University, Quebec, Canada; 7University of North Carolina, Wilmington, NC, USAAbstract: Sleep problems are highly prevalent in cancer patients undergoing chemotherapy. This article reviews existing evidence on etiology, associated symptoms, and management of sleep problems associated with chemotherapy treatment during cancer. It also discusses limitations and methodological issues of current research. The existing literature suggests that subjectively and objectively measured sleep problems are the highest during the chemotherapy phase of cancer treatments. A possibly involved mechanism reviewed here includes the rise in the circulating proinflammatory cytokines and the associated disruption in circadian rhythm in the development and maintenance of sleep dysregulation in cancer patients during chemotherapy. Various approaches to the management of sleep problems during chemotherapy are discussed with behavioral intervention showing promise. Exercise, including yoga, also appear to be effective and safe at least for subclinical levels of sleep problems in cancer patients. Numerous challenges are associated with conducting research on sleep in cancer patients during chemotherapy treatments and they are discussed in this review. Dedicated intervention trials, methodologically sound and sufficiently powered, are needed to test current and novel treatments of sleep problems in cancer patients receiving chemotherapy. Optimal management of sleep problems in patients with cancer receiving treatment may improve not only the well-being of patients, but also their prognosis given the emerging experimental and clinical evidence suggesting that sleep disruption might adversely impact treatment and recovery from cancer.Keywords: cancer, sleep, chemotherapy, intervention, circadian rhythm, cognitive behavioral therapy

Background: Cancer-related fatigue is a debilitating symptom affecting psychosocial functioning and quality of life in 70% to 100% of cancer patients during and after treatment. The authors examined the effect of 200 mg of modafinil daily on the severity of cancer-related fatigue.Methods: The authors conducted a multicenter, randomized, double-blind, placebo-controlled, phase 3, clinical trial to examine the effect of modafinil on patient-reported fatigue in cancer patients undergoing chemotherapy. A sample of 877 cancer patients beginning chemotherapy at 23 geographically separate University of Rochester Cancer Center (URCC) Community Clinical Oncology Program (CCOP) affiliates were assessed for fatigue. Patients who reported fatigue (N=867) were randomly assigned to receive either 200 mg of oral modafinil (Provigil) daily or a placebo. Treatment began on Day 5 of Cycle 2 and ended after Day 7 of Cycle 4. Fatigue and depression were assessed during Cycles 2 to 4 by using psychometrically valid measures. Group differences (treatment vs control) in the worst level of fatigue during the previous week at Cycle 4 were examined by using an analysis of covariance (ANCOVA) adjusting for baseline fatigue (Cycle 2).Results: There were 631 patients (315 modafinil, 316 placebo) who provided evaluable data. ANCOVA showed a significant interaction between treatment condition and baseline fatigue (P=.017), where patients with severe baseline fatigue (n=458) benefited from modafinil, whereas patients with mild or moderate fatigue did not. Modafinil had no statistically significant effect on depression (P>.05).Conclusions: Modafinil may be useful in controlling cancer-related fatigue in patients who present with severe fatigue but is not useful in patients with mild or moderate fatigue. [ABSTRACT FROM AUTHOR]

Abstract Background Alzheimer's disease is a complex neurodegenerative disorder characterized pathologically by a temporal and spatial progression of beta-amyloid (Aβ) deposition, neurofibrillary tangle formation, and synaptic degeneration. Inflammatory processes have been implicated in initiating and/or propagating AD-associated pathology within the brain, as inflammatory cytokine expression and other markers of inflammation are pronounced in individuals with AD pathology. The current study examines whether inflammatory processes are evident early in the disease process in the 3xTg-AD mouse model and if regional differences in inflammatory profiles exist. Methods Coronal brain sections were used to identify Aβ in 2, 3, and 6-month 3xTg-AD and non-transgenic control mice. Quantitative real-time RT-PCR was performed on microdissected entorhinal cortex and hippocampus tissue of 2, 3, and 6-month 3xTg-AD and non-transgenic mice. Microglial/macrophage cell numbers were quantified using unbiased stereology in 3xTg-AD and non-transgenic entorhinal cortex and hippocampus containing sections. Results We observed human Aβ deposition at 3 months in 3xTg-AD mice which is enhanced by 6 months of age. Interestingly, we observed a 14.8-fold up-regulation of TNF-α and 10.8-fold up-regulation of MCP-1 in the entorhinal cortex of 3xTg-AD mice but no change was detected over time in the hippocampus or in either region of non-transgenic mice. Additionally, this increase correlated with a specific increase in F4/80-positive microglia and macrophages in 3xTg-AD entorhinal cortex. Conclusion Our data provide evidence for early induction of inflammatory processes in a model that develops amyloid and neurofibrillary tangle pathology. Additionally, our results link inflammatory processes within the entorhinal cortex, which represents one of the earliest AD-affected brain regions.

Purpose: The primary goal of this scoping review was to summarize the literature published after the 2018 National Cancer Institute think tank, "Measuring Aging and Identifying Aging Phenotypes in Cancer Survivors," on physical and cognitive functional outcomes among cancer survivors treated with chemotherapy. We focused on the influence of chemotherapy on aging-related outcomes (i.e., physical functional outcomes, cognitive functional outcomes, and frailty), given the known associations between chemotherapy and biologic mechanisms that affect aging-related physiologic processes., Methods: A search was conducted across electronic databases, including PubMed, Scopus, and Web of Science, for manuscripts published between August 2018 and July 2023. Eligible studies: 1) included physical function, cognitive function, and/or frailty as outcomes; 2) included cancer survivors (as either the whole sample or a subgroup); 3) reported on physical or cognitive functional outcomes and/or frailty related to chemotherapy treatment (as either the whole sample or a subgroup); and 4) were observational in study design., Results: The search yielded 989 potentially relevant articles, of which 65 met the eligibility criteria. Of the 65 studies, 49 were longitudinal, and 16 were cross-sectional; 30 studies (46%) focused on breast cancer, 20 studies (31%) focused on the age group 60 + years, and 17 (26%) focused on childhood cancer survivors. With regards to outcomes, 82% of 23 studies reporting on physical function showed reduced physical function, 74% of 39 studies reporting on cognitive functional outcomes found reduced cognitive function, and 80% of 15 studies reporting on frailty found increasing frailty among cancer survivors treated with chemotherapy over time and/or compared to individuals not treated with chemotherapy. Fourteen studies (22%) evaluated biologic mechanisms and their relationship to aging-related outcomes. Inflammation was consistently associated with worsening physical and cognitive functional outcomes and epigenetic age increases. Further, DNA damage was consistently associated with worse aging-related outcomes., Conclusion: Chemotherapy is associated with reduced physical function, reduced cognitive function, and an increase in frailty in cancer survivors; these associations were demonstrated in longitudinal and cross-sectional studies. Inflammation and epigenetic age acceleration are associated with worse physical and cognitive function; prospective observational studies with multiple time points are needed to confirm these findings., Implications for Cancer Survivors: This scoping review highlights the need for interventions to prevent declines in physical and cognitive function in cancer survivors who have received chemotherapy., (© 2024. The Author(s).)

Background: Androgen deprivation therapy (ADT) inhibits prostate cancer growth. However, ADT causes loss of bone mineral density (BMD) and an increase in fracture risk; effective interventions for ADT-induced bone loss are limited., Methods: A phase 2 randomized controlled trial investigated the feasibility, safety, and preliminary efficacy of high-dose weekly vitamin D (HDVD, 50,000 IU/week) versus placebo for 24 weeks in patients with prostate cancer receiving ADT, with all subjects receiving 600 IU/day vitamin D and 1000 mg/day calcium. Participants were ≥60 years (mean years, 67.7), had a serum 25-hydroxyvitamin D level <32 ng/mL, and initiated ADT within the previous 6 months. At baseline and after intervention, dual-energy x-ray absorptiometry was used to assess BMD, and levels of bone cell, bone formation, and resorption were measured., Results: The HDVD group (N = 29) lost 1.5% BMD at the total hip vs. 4.1% for the low-dose group (N = 30; p = .03) and 1.7% BMD at the femoral neck vs. 4.4% in the low-dose group (p = .06). Stratified analyses showed that, for those with baseline 25-hydroxyvitamin D level <27 ng/mL, the HDVD group lost 2.3% BMD at the total hip vs 7.1% for the low-dose group (p < .01). Those in the HDVD arm showed significant changes in parathyroid hormone (p < .01), osteoprotegerin (p < 0.01), N-terminal telopeptide of type 1 collagen (p < 0.01) and C-terminal telopeptide of type 1 collagen (p < 0.01). No difference in adverse events or toxicity was noted between the groups., Conclusions: HDVD supplementation significantly reduced hip and femoral neck BMD loss, especially for patients with low baseline serum 25-hydroxyvitamin D levels, although demonstrating safety and feasibility in prostate cancer patients on ADT., (© 2024 American Cancer Society.)

Cancer remains a formidable global health challenge, with metastasis being a key contributor to its lethality. Abundant high molecular mass hyaluronic acid, a major non-protein component of extracellular matrix, protects naked mole rats from cancer and reduces cancer incidence in mice. Hyaluronidase plays a critical role in degrading hyaluronic acid and is frequently overexpressed in metastatic cancer. Here we investigated the potential of targeting hyaluronidases to reduce metastasis. A high throughput screen identified delphinidin, a natural plant compound found in fruits and vegetables, as a potent hyaluronidase inhibitor. Delphinidin-mediated inhibition of hyaluronidase activity led to an increase in high molecular weight hyaluronic acid in cell culture and in mouse tissues, and reduced migration and invasion behavior of breast, prostate, and melanoma cancer cells. Moreover, delphinidin treatment suppressed melanoma metastasis in mice. Our study provides a proof of principle that inhibition of hyaluronidase activity suppresses cancer cell migration, invasion and metastasis. Furthermore, we identified a natural compound delphinidin as a potential anticancer therapeutic. Thus, we have identified a path for clinical translation of the cancer resistance mechanism identified in the naked mole rat., (© 2024. The Author(s).)

The number of adults aged ≥ 65 years with cancer is rapidly increasing. Older adults with cancer are susceptible to treatment-related acute and chronic adverse events, resulting in loss of independence, reduction in physical function, and decreased quality of life. Nevertheless, evidence-based interventions to prevent or treat acute and chronic adverse events in older adults with cancer are limited. Several promising blood-based biomarkers related to inflammation and epigenetic modifications are available to identify older adults with cancer who are at increased risk of accelerated aging and physical, functional, and cognitive impairments caused by the cancer and its treatment. Inflammatory changes and epigenetic modifications can be reversible and targeted by lifestyle changes and interventions. Here we discuss ways in which changes in inflammatory and epigenetic pathways influence the aging process and how these pathways can be targeted by interventions aimed at reducing inflammation and aging-associated biological markers. As the number of older adults with cancer entering survivorship continues to increase, it is becoming progressively more important to understand ways in which the benefit from treatment can be enhanced while reducing the effects of accelerated aging., Competing Interests: Declaration of Competing Interest KPL reports receiving consulting fees from Pfizer and Seattle Genetics and an honorarium from Pfizer. GL reports receiving honoraria from Nutricia As and Servier and travel support from Servier. SPA reports receiving honoraria from Exelixis, QED Therapeutics, AstraZeneca, and Seagen and travel support from DAVA Oncology., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Although data are limited, difficulty in social cognition occurs in up to 83% of patients with brain tumors. It is unknown whether cranial radiation therapy (RT) dose to the amygdala-orbitofrontal network can impact social cognition., Methods: We prospectively enrolled 51 patients with low-grade and benign brain tumors planned for cranial RT. We assessed longitudinal changes on an emotion recognition task (ERT) that measures the ability to recognize emotional states by displaying faces expressing six basic emotions and their association with the RT dose to the amygdala-orbitofrontal network. ERT outcomes included the median time to choose a response (ERTOMDRT) or correct response (ERTOMDCRT) and total correct responses (ERTHH)., Results: The RT dose to the amygdala-orbitofrontal network was significantly associated with longer median response times on the ERT. Increases in median response times occurred at lower doses than decreases in total correct responses. The medial orbitofrontal cortex was the most important variable on regression trees predicting change in the ERTOMDCRT., Discussion: This is, to our knowledge, the first study to show that off-target RT dose to the amygdala-orbitofrontal network is associated with performance on a social cognition task, a facet of cognition that has previously not been mechanistically studied after cranial RT.

Treatment modalities for breast cancer, including cyclophosphamide chemotherapy, have been associated with the development of cognitive decline (CRCD), which is characterized by impairments in memory, concentration, attention, and executive functions. We and others have identified a link between inflammation and decreased cognitive performance in patients with breast cancer receiving chemotherapy. In order to better understand the inflammation-associated molecular changes within the brain related to tumor alone or in combination with chemotherapy, we orthotopically implanted mouse mammary tumors (E0771) into female C57BL/6 mice and administered clinically relevant doses of cyclophosphamide and doxorubicin intravenously at weekly intervals for four weeks. We measured serum cytokines and markers of neuroinflammation at 48 h and up to one month post-treatment and tested memory using a reward-based delayed spatial alternation paradigm. We found that breast tumors and chemotherapy altered systemic inflammation and neuroinflammation. We further found that the presence of tumor and chemotherapy led to a decline in memory over time at the longest delay, when memory was the most taxed, compared to shorter delay times. These findings in a clinically relevant mouse model shed light on possible biomarkers for CRCD and add to the growing evidence that anti-inflammatory strategies have the potential to mitigate cancer- or treatment-related side effects., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Cancer survivors over the age of 65 have unique needs due to the higher prevalence of functional and cognitive impairment, comorbidities, geriatric syndromes, and greater need for social support after chemotherapy. In this study, we will evaluate whether a Geriatric Evaluation and Management-Survivorship (GEMS) intervention improves functional outcomes important to older cancer survivors following chemotherapy., Methods: A cluster-randomized trial will be conducted in approximately 30 community oncology practices affiliated with the University of Rochester Cancer Center (URCC) National Cancer Institute Community Oncology Research Program (NCORP) Research Base. Participating sites will be randomized to the GEMS intervention, which includes Advanced Practice Practitioner (APP)-directed geriatric evaluation and management (GEM), and Survivorship Health Education (SHE) that is combined with Exercise for Cancer Patients (EXCAP©®), or usual care. Cancer survivors will be recruited from community oncology practices (of participating oncology physicians and APPs) after the enrolled clinicians have consented and completed a baseline survey. We will enroll 780 cancer survivors aged 65 years and older who have completed curative-intent chemotherapy for a solid tumor malignancy within four weeks of study enrollment. Cancer survivors will be asked to choose one caregiver to also participate for a total up to 780 caregivers. The primary aim is to compare the effectiveness of GEMS for improving patient-reported physical function at six months. The secondary aim is to compare effectiveness of GEMS for improving patient-reported cognitive function at six months. Tertiary aims include comparing the effectiveness of GEMS for improving: 1) Patient-reported physical function at twelve months; 2) objectively assessed physical function at six and twelve months; and 3) patient-reported cognitive function at twelve months and objectively assessed cognitive function at six and twelve months. Exploratory health care aims include: 1) Survivor satisfaction with care, 2) APP communication with primary care physicians (PCPs), 3) completion of referral appointments, and 4) hospitalizations at six and twelve months. Exploratory caregiver aims include: 1) Caregiver distress; 2) caregiver quality of life; 3) caregiver burden; and 4) satisfaction with patient care at six and twelve months., Discussion: If successful, GEMS would be an option for a standardized APP-led survivorship care intervention., Trial Registration: ClinicalTrials.govNCT05006482, registered on August 9, 2021., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: We have shown the Exercise for Cancer Patients (EXCAP ©® ) exercise program improved physical function and symptoms and reduced inflammatory markers in patients with cancer. However, adherence to exercise was lower in older adults compared to their younger counterparts. We then leveraged a mobile app to deliver EXCAP ©® and adapted the intervention [Geriatric-Oncology (GO)-EXCAP] for older patients with myeloid neoplasms. In this pilot randomized trial, the primary goal is to determine effect sizes. We propose to assess the preliminary efficacy of GO-EXCAP compared to a behavioral placebo control on physical function, patient-reported outcomes (fatigue, mood, and quality of life), and inflammatory markers in 100 patients aged ≥60 years with myeloid neoplasms receiving outpatient chemotherapy., Methods: GO-EXCAP consists of the EXCAP ©® exercise prescription (daily home-based progressive aerobic walking and resistance exercises with rated perceived exercise of 5-8), EXCAP ©® kit (i.e., activity tracker, resistance bands, print manual, bag), a mobile app, and an in-person or virtual session with the exercise physiologist to deliver exercise prescription. The intervention will last for three cycles of chemotherapy (approximately 12 weeks). The primary outcome measure will be physical function (Short Physical Performance Battery). Secondary outcome measures include fatigue (Brief Fatigue Inventory), mood (Center for Epidemiologic Studies Depression Scale), and quality of life (Functional Assessment of Cancer Therapy-Leukemia). Exploratory outcome measures include inflammatory markers., Discussion: Older adults with myeloid neoplasms receiving outpatient chemotherapy serve as an ideal model for studying an individually tailored mobile health exercise intervention in vulnerable older patients receiving cancer treatments to prevent physical function decline and improve symptoms., Competing Interests: Declaration of Competing Interest Dr. Loh has served as a consultant to Pfizer and Seattle Genetics, and has received honoraria from Pfizer. All other authors have no relevant conflicts of interest to report., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background and Purpose: Genome-wide association studies (GWAS) of late hematuria following prostate cancer radiotherapy identified single nucleotide polymorphisms (SNPs) near AGT, encoding angiotensinogen. We tested the hypothesis that patients taking angiotensin converting enzyme inhibitors (ACEi) have a reduced risk of late hematuria. We additionally tested genetically-defined hypertension., Materials and Methods: Prostate cancer patients undergoing potentially-curative radiotherapy were enrolled onto two multi-center observational studies, URWCI (N = 256) and REQUITE (N = 1,437). Patients were assessed pre-radiotherapy and followed prospectively for development of toxicity for up to four years. The cumulative probability of hematuria was estimated by the Kaplan-Meier method. Multivariable grouped relative risk models assessed the effect of ACEi on time to hematuria adjusting for clinical factors and stratified by enrollment site. A polygenic risk score (PRS) for blood pressure was tested for association with hematuria in REQUITE and our Radiogenomics Consortium GWAS., Results: Patients taking ACEi during radiotherapy had a reduced risk of hematuria (HR 0.51, 95%CI 0.28 to 0.94, p = 0.030) after adjusting for prior transurethral prostate and/or bladder resection, heart disease, pelvic node radiotherapy, and bladder volume receiving 70 Gy, which are associated with hematuria. A blood pressure PRS was associated with hypertension (odds ratio per standard deviation 1.38, 95%CI 1.31 to 1.46, n = 5,288, p < 0.001) but not hematuria (HR per standard deviation 0.96, 95%CI 0.87 to 1.06, n = 5,126, p = 0.41)., Conclusions: Our study is the first to show a radioprotective effect of ACEi on bladder in an international, multi-site study of patients receiving pelvic radiotherapy. Mechanistic studies are needed to understand how targeting the angiotensin pathway protects the bladder., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: A geriatric assessment (GA) intervention improves communication about aging-related concerns, but its effect on communication in patients with various levels of frailty is unknown., Methods: This was a secondary analysis of a nationwide trial of patients aged ≥70 years with incurable cancer and impairment on 1 or more GA domains (ClinicalTrials.gov Identifier NCT02107443; principal investigator Supriya G. Mohile). Practice sites were randomized to either the GA-intervention or usual care. Frailty was assessed with a deficit accumulation index (range, 0-1), and patients were stratified as robust (0 to <0.2), prefrail (0.2 to <0.35), or frail (≥0.35). The clinic visit after the GA-intervention was audio-recorded, transcribed, and coded to evaluate the number and quality of conversations about aging-related concerns. Linear mixed models examined differences in the number and quality of conversations within and between arms. All P values were 2-sided., Results: Patients (n = 541) were classified as robust (27%), prefrail (42%), or frail (31%). In the usual care arm, frail patients (vs robust ones) engaged in more aging-related conversations (adjusted mean difference, 1.73; 95% confidence interval [CI], 0.59-2.87), conversations of higher quality (difference, 1.12; 95% CI, 0.24-2.0), and more discussions about evidence-based recommendations (difference, 0.71; 95% CI, 0.04-1.38; all P values ≤ .01). Similarly, in the GA intervention arm, frail patients (vs robust ones) engaged in more aging-related conversations (difference, 2.49; 95% CI, 1.51-3.47), conversations of higher quality (difference, 1.31; 95% CI, 0.56-2.06), and more discussions about evidence-based recommendations (difference, 0.87; 95% CI, 0.32-1.42; all P values ≤ .01). Furthermore, the GA-intervention significantly improved the number and quality of conversations in all patients: robust, prefrail, and frail (all P values ≤ .01)., Conclusions: Patients with higher degrees of frailty and those exposed to the GA-intervention had more and higher quality conversations about aging-related concerns with oncologists., Lay Summary: A geriatric assessment (GA) intervention improves communication about aging-related concerns, but its effect on communication in patients with various levels of frailty is unknown. This study conducted a secondary analysis of a nationwide trial of patients aged ≥70 years with incurable cancer and 1 or more GA domain impairments. Patients were stratified as robust, prefrail, or frail. The number and quality of conversations about aging-related concerns that occurred during the clinic visit after the GA-intervention were determined. Patients with higher degrees of frailty and those in the GA intervention arm had more and higher quality conversations about aging-related concerns with oncologists., (© 2021 American Cancer Society.)

Background: Older adults with advanced cancer are at a high risk for treatment toxic effects. Geriatric assessment evaluates ageing-related domains and guides management. We examined whether a geriatric assessment intervention can reduce serious toxic effects in older patients with advanced cancer who are receiving high risk treatment (eg, chemotherapy)., Methods: In this cluster-randomised trial, we enrolled patients aged 70 years and older with incurable solid tumours or lymphoma and at least one impaired geriatric assessment domain who were starting a new treatment regimen. 40 community oncology practice clusters across the USA were randomly assigned (1:1) to the intervention (oncologists received a tailored geriatric assessment summary and management recommendations) or usual care (no geriatric assessment summary or management recommendations were provided to oncologists) by means of a computer-generated randomisation table. The primary outcome was the proportion of patients who had any grade 3-5 toxic effect (based on National Cancer Institute Common Terminology Criteria for Adverse Events version 4) over 3 months. Practice staff prospectively captured toxic effects. Masked oncology clinicians reviewed medical records to verify. The study was registered with ClinicalTrials.gov, NCT02054741., Findings: Between July 29, 2014, and March 13, 2019, we enrolled 718 patients. Patients had a mean age of 77·2 years (SD 5·4) and 311 (43%) of 718 participants were female. The mean number of geriatric assessment domain impairments was 4·5 (SD 1·6) and was not significantly different between the study groups. More patients in intervention group compared with the usual care group were Black versus other races (40 [11%] of 349 patients vs 12 [3%] of 369 patients; p<0·0001) and had previous chemotherapy (104 [30%] of 349 patients vs 81 [22%] of 369 patients; p=0·016). A lower proportion of patients in the intervention group had grade 3-5 toxic effects (177 [51%] of 349 patients) compared with the usual care group (263 [71%] of 369 patients; relative risk [RR] 0·74 (95% CI 0·64-0·86; p=0·0001). Patients in the intervention group had fewer falls over 3 months (35 [12%] of 298 patients vs 68 [21%] of 329 patients; adjusted RR 0·58, 95% CI 0·40-0·84; p=0·0035) and had more medications discontinued (mean adjusted difference 0·14, 95% CI 0·03-0·25; p=0·015)., Interpretation: A geriatric assessment intervention for older patients with advanced cancer reduced serious toxic effects from cancer treatment. Geriatric assessment with management should be integrated into the clinical care of older patients with advanced cancer and ageing-related conditions., Funding: National Cancer Institute., Competing Interests: Declaration of interests KPL reports consultant fees from Pfizer and Seattle Genetics and honoraria from Pfizer. RFD received honoraria for consulting from Exelixis. TW reports research funding from Janssen and consultant fees from Seattle Genetics and Carevive. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Older patients with myeloid neoplasms (MN) receiving outpatient chemotherapy are at risk of experiencing treatment-related toxicities such as functional decline. A mobile health (mHealth) exercise intervention may ameliorate these toxicities. This qualitative study aimed to inform the design of a mHealth exercise intervention for this population., Methods: This was a qualitative study of thirteen patients aged ≥60 years receiving hypomethylating agents for MN. EXCAP©® is a home-based walking and progressive resistance exercise program. We combined EXCAP©® with a mobile app; the combination (GO-EXCAP Mobile App) has not been previously tested. A brief verbal description about the intervention was provided to the participants but they did not perform it. Participants were interviewed and inductive thematic analysis was used to analyze the data., Results: Mean age was 71.6 (SD 8.5). Three themes were identified: 1) Perceptions of the intervention feasibility, 2) Ways to leverage the app to deliver the exercise intervention, and 3) Personalized exercise goals. Walking and resistance exercises were perceived to be feasible. Patients were comfortable initiating the intervention in cycle 2 of chemotherapy, with exercise increments occurring from week 2-4 of the cycle. Ways to leverage the app to deliver EXCAP©® include 1) Video feature for exercise demonstration and interactions, and 2) Exercise data and symptom surveys to be communicated to the exercise physiologist and primary oncology team. Preservation of existing function and activity was an important goal to participants., Conclusions: Our findings provide insights about the preferences of older adults with MN for a mHealth exercise intervention., Competing Interests: Declaration of Competing Interest Dr. Loh serves as a consultant to Pfizer and Seattle Genetics. Dr. Mohile received research funding from Carevive for other projects. All other authors have no relevant conflicts of interest to report., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Cancer-related cognitive impairment (CRCI) is commonly experienced by individuals with non-central nervous system cancers throughout the disease and treatment trajectory. CRCI can have a substantial impact on the functional ability and quality of life of patients and their families. To mitigate the impact, oncology providers must know how to identify, assess, and educate patients and caregivers. The objective of this review is to provide oncology clinicians with an overview of CRCI in the context of adults with non-central nervous system cancers, with a particular focus on current approaches in its identification, assessment, and management.

Background: Frailty is associated with an increased risk of chemotherapy toxicity. Cellular markers of inflammation can help identify patients with frailty characteristics. However, the role of cellular markers of inflammation in identifying patients at risk of developing chemotherapy-induced frailty and their clinical utility are not fully understood., Methods: This study was a secondary analysis of a large nationwide cohort study of women with stage I-IIIC breast cancer (n = 581, mean age 53.4; range 22-81). Measures were completed pre-chemotherapy (T1), post-chemotherapy (T2), and 6 months post-chemotherapy (T3). Frailty was assessed at all three time points using a modified Fried score consisting of four self-reported measures (weakness, exhaustion, physical activity, and walking speed; 0-4, 1 point for each). Immune cell counts as well as neutrophil to lymphocyte ratio (NLR) and lymphocyte to monocyte ratio (LMR) were obtained at T1 and T2 time points. Separate linear regressions were used to evaluate the associations of (1) cell counts at T1 with frailty at T1, T2, and T3 and (2) change in cell counts (T2-T1) with frailty at T2 and T3. We controlled for relevant covariates and frailty at the T1 time point., Results: From T1 to T2, the mean frailty score increased (1.3 vs 2.0; p < 0.01) and returned to T1 levels by the T3 time point (1.3 vs 1.3; p = 0.85). At the T1 time point, there was a positive association between cellular markers of inflammation and frailty: WBC (β = 0.04; p < 0.05), neutrophils (β = 0.04; p < 0.05), and NLR (β = 0.04; p < 0.01). From T1 to T2, a greater increase in cellular markers of inflammation was associated with frailty at T2 (WBC: β = 0.02, p < 0.05; neutrophils: β = 0.03, p < 0.05; NLR: β = 0.03; p < 0.01). These associations remained significant after controlling for the receipt of growth factors with chemotherapy and the time between when laboratory data was provided and the start or end of chemotherapy., Conclusions: In patients with breast cancer undergoing chemotherapy, cellular markers of inflammation are associated with frailty. Immune cell counts may help clinicians identify patients at risk of frailty during chemotherapy., Trial Registration: ClinicalTrials.gov , NCT01382082.