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Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is common and disabling among cancer survivors. Little is known about the association of CIPN with other measures of the nervous system's integrity, such as executive dysfunction. We compared measures of executive function in older chemotherapy-treated cancer survivors with and without CIPN., Materials and Methods: This cross-sectional study enrolled 50 chemotherapy-treated cancer survivors (65.6 ± 11.5 years, 88% female) post-chemotherapy treatment who were previously referred for outpatient rehabilitation at the request of the cancer survivor or a medical provider. Twenty-two participants (44%) had CIPN defined by patient-reported distal paresthesia or numbness, which began with chemotherapy and continued to the time of cognitive testing. Measures of executive function included Trails-B, Stroop, and rapid reaction accuracy (RRA) and were evaluated between cancer survivors with and without CIPN using t-tests. Multivariable models were then used to determine whether CIPN was an independent determinant of the measures of executive function (Trails-B, Stroop Incongruent, and RRA). Models were adjusted for age, sex, history of anxiety, and benzodiazepine use due to their known associations with CIPN and executive function., Results: Cancer survivors with CIPN (CIPN+) had reduced executive function compared to survivors without CIPN (CIPN-) on Trails-B (CIPN+: 84.9 s ± 44.1 s, CIPN-: 59.1 s ± 22.5 s, p = 0.01), Stroop (CIPN+: 100.6 s ± 38.2 s, CIPN-: 82.1 s ± 17.3 s, p = 0.03), and RRA (CIPN+: 60.3% ± 12.9%, CIPN-: 70.6% ± 15.7%, p = 0.01). There were no differences in cancer stage severity or functional status by patient report or sit-to-stand function. The association between CIPN and reduced executive function was found in multivariable models after adjusting for age, sex, anxiety, and benzodiazepine use for Trails-B (ß:17.9, p = 0.046), Stroop (ß:16.9, p = 0.02), and RRA (ß:-0.072, p = 0.03)., Discussion: In this population, CIPN is associated with reduced executive function in older cancer survivors treated with chemotherapy. Future research is required to further understand this preliminary association, the causality, and the potential risk factors., Competing Interests: Declaration of Competing Interest MKH reports receiving consulting fees from Argenx, Alexion, UCB Pharma, Janssen, and Immunovant; honoraria from Medscape, Springer Health, AANEM, Medlink Neurology, and Continuum Lifelong Learning in Neurology; grants from University of Vermont Medical Center and Myasthenia Gravis Foundation of America; and leadership roles in the Neuromuscular Study Group and AANEM Neuromuscular Fellowship Committee. NK reports funding from the National Cancer Institute; receiving consulting fees from the Eisana Corporation; and receiving honoraria from AANEM. JKR reports funding from the Newman Family Foundation; payment for expert testimony; sharing a patent for the ReacStick with colleagues James Ashton-Miller, James T. Eckner, and Hogene Kim., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: The study aimed to determine the feasibility of remotely delivered exercise (tele-exercise) for older, rural cancer survivors and to explore the effects of tele-exercise on physical function, physical activity, and patient-reported outcomes., Methods: Participants were rural cancer survivors age ≥ 60 years (79% female; mean age 70.4 ± 5.7) randomly assigned to the remotely delivered EnhanceFitness (tele-EF) exercise program, inclusive of aerobic, strength, and balance training and led by American Council on Exercise certified instructors for 1 h, 3 days/week for 16 weeks (n = 20) or to a waitlist control group (n = 19). We assessed feasibility, physical function, accelerometer-measured physical activity, and patient-reported outcomes at baseline and post intervention., Results: Among those screened as eligible, 44 (64%) consented to participate with 39 randomized after completing baseline measures. Attrition was equivalent between groups (n = 1, each) with 95% completing the study. The median class attendance rate was 86.9% (interquartile range: 79-94%). Compared to controls, tele-EF participants had statistically significant improvement in the five-time sit-to-stand test (- 3.4 vs. - 1.1 s, p = 0.03, effect size = 0.44), mean daily light physical activity (+ 38.5 vs 0.5 min, p = 0.03, effect size = 0.72) and step counts (+ 1977 vs. 33, p = 0.01, effect size = 0.96). There were no changes in self-efficacy for exercise, fatigue, or sleep disturbance between groups., Conclusions: Findings indicate that tele-EF is feasible in older, rural cancer survivors and results in positive changes in physical function and physical activity., Implications for Cancer Survivors: Tele-EF addresses common barriers to exercise for older, rural cancer survivors, including limited accessible opportunities for professional instruction and supervision., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: Declaration of Competing Interest BLM, KM, JM, NK, JAS, HC, MKH, RR, SGB, MR, CR, JKR, NK report no conflicts of interest with the current manuscript. NK reports receiving consulting fees from Eisana Corporation as a medical consultant and honoraria for lectures from AANEM. MKH reports receiving consulting fees from Argenx, Alexion, UCB Pharma, Janssen, and Immunovant and honoraria from Medscape, Springer Health, AANEM, Medlink Neurology, and Continuum Lifelong Learning in Neurology.

Background: Previous studies identified physical function limitations in older cancer survivors, but few have included objective measures and most focused on breast and prostate cancer survivors. The current study compared patient-reported and objective physical function measures between older adults with and without a cancer history., Methods: Our cross-sectional study used a nationally representative sample of community-dwelling, Medicare beneficiaries from the 2015 National Health and Aging Trends Study (n = 7495). Data collected included patient-reported physical function, including a composite physical capacity score and limitations in strength, mobility, and balance, and objectively measured physical performance metrics, including gait speed, five time sit-to-stand, tandem stand, and grip strength. All analyses were weighted to account for the complex sampling design., Results: Thirteen percent of participants (n = 829) reported a history of cancer, of which more than half (51%) reported a diagnosis other than breast or prostate cancer. In models adjusted for demographics and health history, older cancer survivors had lower Short Physical Performance Battery scores (unstandardized beta [B] = -0.36; 95% CI: -0.64, -0.08), slower gait speed (B = -0.03; 95% CI: -0.05, -0.01), reduced grip strength (B = -0.86; 95% CI: -1.44, -0.27), worse patient-reported composite physical capacity (B = -0.43; 95% CI: -0.67, -0.18) and patient-reported upper extremity strength (B = 1.27; 95% CI: 1.07, 1.50) compared to older adults without cancer. Additionally, the burden of physical function limitations was greater in women than in men, which may be explained by cancer type., Conclusions: Our results extend studies in breast and prostate cancer to show worse objective and patient-reported physical function outcomes in older adults with a range of cancer types compared to those without a cancer history. Moreover, these burdens seem to disproportionately affect older adult women, underscoring the need for interventions to address functional limitations and prevent further health consequences of cancer and its treatment., (© 2023 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

Introduction: Balance decrements and increased fall risk in older cancer survivors have been attributed to chemotherapy-induced peripheral neuropathy (CIPN). Cognition is also affected by chemotherapy and may be an additional contributing factor to poor balance through changes in executive functioning. We examined the association of executive function with balance and falls in older cancer survivors who had been treated with chemotherapy., Materials and Methods: Fifty cancer survivors (aged 65.6 ± 11.5 years; 88% female) who were all treated with chemotherapy were included in this cross-sectional study at a tertiary medical center. Executive function was measured by Trails-B, Stroop, and rapid reaction accuracy, a measure emphasizing rapid inhibitory function. Balance was measured by five sit-to-stand time (5STS), repetitions of sit-to-stand in thirty seconds (STS30), and unipedal stance time (UST), which was the primary balance outcome measure. Self-reported falls in the past year were also recorded and was a secondary outcome. Bivariate analyses were conducted between executive function measures and balance variables. Multivariable models were constructed for UST and falls outcomes and included covariates of age and chemotherapy induced peripheral neuropathy status., Results: Pearson correlations demonstrated significant relationships between two executive function measures (rapid reaction accuracy, Trails-B) and all the balance measures assessed (UST, STS30, and 5STS). Rapid reaction accuracy correlations were stronger than Trails-B. The Stroop measure correlated solely with UST. In multivariable models, rapid reaction accuracy was associated with better UST (standardized regression coefficient: 64.1, p < 0.01), decreased any fall (odds ratio = 0.000901, p = 0.04), and decreased recurrent falls (odds ratio = 0.0000044, p = 0.01). The interaction of CIPN with the inhibitory measures in the prediction of balance was not significant., Discussion: Measures of executive function were associated with balance, but among the executive function tests, rapid reaction accuracy had the strongest correlations to balance and was independently associated with falls. The findings suggest that executive function should be considered when assessing fall risk and developing interventions intended to reduce fall risk in older chemotherapy-treated cancer survivors., Competing Interests: Declaration of Competing Interest BLM, KM, JM, NK, JAS, HC, MKH, RR, MR, CR, JKR, NK report no conflicts of interest with the current manuscript., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Brain gray matter (GM) reductions have been reported after breast cancer chemotherapy, typically in small and/or cross-sectional cohorts, most commonly using voxel-based morphometry (VBM). There has been little examination of approaches such as deformation-based morphometry (DBM), machine-learning-based brain aging metrics, or the relationship of clinical and demographic risk factors to GM reduction. This international data pooling study begins to address these questions. Participants included breast cancer patients treated with (CT+, n = 183) and without (CT-, n = 155) chemotherapy and noncancer controls (NC, n = 145), scanned pre- and post-chemotherapy or comparable intervals. VBM and DBM examined GM volume. Estimated brain aging was compared to chronological aging. Correlation analyses examined associations between VBM, DBM, and brain age, and between neuroimaging outcomes, baseline age, and time since chemotherapy completion. CT+ showed longitudinal GM volume reductions, primarily in frontal regions, with a broader spatial extent on DBM than VBM. CT- showed smaller clusters of GM reduction using both methods. Predicted brain aging was significantly greater in CT+ than NC, and older baseline age correlated with greater brain aging. Time since chemotherapy negatively correlated with brain aging and annual GM loss. This large-scale data pooling analysis confirmed findings of frontal lobe GM reduction after breast cancer chemotherapy. Milder changes were evident in patients not receiving chemotherapy. CT+ also demonstrated premature brain aging relative to NC, particularly at older age, but showed evidence for at least partial GM recovery over time. When validated in future studies, such knowledge could assist in weighing the risks and benefits of treatment strategies., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We aimed to examine exercise intensity among older adults participating from home in remotely delivered EnhanceFitness (Tele-EF). Exercise intensity was assessed through Fitbit-measured heart rate and the Borg 10-point rating of perceived exertion over 1 week of a 16-week exercise program. Outcomes included mean minutes spent at or above the heart rate reserve calculated threshold for moderate intensity and mean rating of perceived exertion. Pearson and Spearman rank correlations were used to examine associations between baseline characteristics with exercise intensity. During the 60-min classes, the 55 participants achieved moderate intensity for a mean of 21.0 min (SD = 13.5) and had a mean rating of perceived exertion of 4.9 (SD = 1.2). There were no significant associations between baseline characteristics and exercise intensity. Older adults can achieve sustained moderate-intensity exercise during Tele-EF supervised classes. Baseline physical function, physical activity, and other health characteristics did not limit ability to exercise at a moderate intensity, though further investigation is warranted.

Virotherapy is a promising, novel form of cancer immunotherapy currently being investigated in pre-clinical and clinical settings. While generally well-tolerated, the anti-tumor potency of oncolytic virus-based monotherapies needs to be improved further. One of the major factors limiting the replication efficiency of oncolytic viruses are the antiviral defense pathways activated by tumor cells. In this study, we have designed and validated a universal expression cassette for artificial microRNAs that can now be adapted to suppress genes of interest, including potential resistance factors. Transcripts are encoded as a primary microRNA for processing via the predominantly nuclear RNase III Drosha. We have engineered an oncolytic measles virus encoding this universal expression cassette for artificial microRNAs. Virally encoded microRNA was expressed in the range of endogenous microRNA transcripts and successfully mediated target protein suppression. However, absolute expression levels of mature microRNAs were limited when delivered by an oncolytic measles virus. We demonstrate that measles virus, in contrast to other cytosolic viruses, does not induce translocation of Drosha from the nucleus into the cytoplasm, potentially resulting in a limited processing efficiency of virus-derived, cytosolically delivered artificial microRNAs. To our knowledge, this is the first report demonstrating functional expression of microRNA from oncolytic measles viruses potentially enabling future targeted knockdown, for instance of antiviral factors specifically in tumor cells.

Executive function (EF) impacts behavior associated with health outcomes. EF can be measured using self-report and/or performance measures, but the correlations between these types of measures are mixed in the extant literature. This study examined self-report and performance-based measures of EF using data from 6 studies, including community and clinical populations (410 participants, ages 19-80, 71% female). Partial correlations revealed significant relationships between performance on the Trail making, Delay Discounting, and Stop Signal tasks with self-reported EF ( p < .006 after controlling for age). Mood scores were significantly related to all self-reported domains of EF ( p < .0001), and mood and EF scores were correlated over time. When also controlling for mood, correlations between delay discounting and stop signal tasks with self-reported EF remained significant ( p < .006). Finally, examining EF scores in participants with and without clinically elevated mood scores showed a wider distribution of self-reported EF scores among those with clinically elevated mood symptoms than among those without. We conclude that self-reported EF is associated with tasks measuring delay discounting and response inhibition in our large, heterogenous population and that assessing EF may be particularly important for those with high levels of mood symptoms.

Purpose: Cyberattacks targeting health care organizations are becoming more frequent and affect all aspects of care delivery. Cancer care is particularly susceptible to major disruptions because of the potential of immediate and long-term consequences for patients who often rely on timely diagnostic testing and regular administration of systemic therapy in addition to other local treatment modalities to cure or control their diseases. On October 28, 2020, a cyberattack was launched on the University of Vermont Health Network with wide-ranging consequences for oncology, including loss of access to all network intranet servers, e-mail communications, and the electronic medical record (EMR)., Methods: This review details the immediate challenges faced by hematology and oncology during the cyberattack. The impact and response on inpatient, outpatient, and special patient populations are described. Steps that other academic- and community-based oncology practices can take to lessen the brunt of such an assault are suggested., Results: The two areas of immediate impact after the cyberattack were communications and lack of EMR access. The oncology-specific impact included loss of the individualized EMR chemotherapy plan templates and electronic safeguards built into multistep treatment preparation and delivery. With loss of access to schedules, basic patient information, encrypted communications platforms and radiology, and laboratory and pharmacy services, clinical outpatient care delivery was reduced by 40%. The infusion visit volume dropped by 52% in the first week and new patients could not access necessary services for timely diagnostic evaluation, requiring the creation of command centers to oversee ethical and transparent triage and allocation of systemic therapies and address new patient referrals. This included appropriate transfer of patients to alternate sites to minimize delays. Inpatient care including transitions of care was particularly challenging and addressing patient populations whose survival might be affected by delays in care., Conclusion: Oncology health care leaders and providers should be aware of the potential impact of a cyberattack on cancer care delivery and preventively develop processes to mitigate the impact., Competing Interests: Steven AdesResearch Funding: Lilly, EMD Serono Alissa A. ThomasResearch Funding: Novocure, Spectrum Pharmaceuticals, Spectrum Pharmaceuticals Julian SpragueStock and Other Ownership Interests: Gilead Sciences, Johnson and Johnson, Merk and Company, Roche/Genentech, Pfizer Peter A. KaufmanStock and Other Ownership Interests: AmgenHonoraria: Lilly, Polyphor, Macrogenics, EisaiConsulting or Advisory Role: Polyphor, Roche/Genentech, Lilly, Eisai, Macrogenics, Pfizer, Merck, AstraZenecaSpeakers' Bureau: LillyResearch Funding: Eisai, Polyphor, Roche/Genentech, Lilly, Novartis, Macrogenics, Pfizer, SanofiTravel, Accommodations, Expenses: Lilly, Polyphor, MacrogenicsNo other potential conflicts of interest were reported.