A scoping review evaluating physical and cognitive functional outcomes in cancer survivors treated with chemotherapy: charting progress since the 2018 NCI think tank on cancer and aging phenotypes.

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.

Management of Fatigue in Adult Survivors of Cancer: ASCO-Society for Integrative Oncology Guideline Update.

PURPOSE: To update the ASCO guideline on the management of cancer-related fatigue (CRF) in adult survivors of cancer. METHODS: A multidisciplinary panel of medical oncology, geriatric oncology, internal medicine, psychology, psychiatry, exercise oncology, integrative medicine, behavioral oncology, nursing, and advocacy experts was convened. Guideline development involved a systematic literature review of randomized controlled trials (RCTs) published in 2013-2023. RESULTS: The evidence base consisted of 113 RCTs. Exercise, cognitive behavioral therapy (CBT), and mindfulness-based programs led to improvements in CRF both during and after the completion of cancer treatment. Tai chi, qigong, and American ginseng showed benefits during treatment, whereas yoga, acupressure, and moxibustion helped to manage CRF after completion of treatment. Use of other dietary supplements did not improve CRF during or after cancer treatment. In patients at the end of life, CBT and corticosteroids showed benefits. Certainty and quality of evidence were low to moderate for CRF management interventions. RECOMMENDATIONS: Clinicians should recommend exercise, CBT, mindfulness-based programs, and tai chi or qigong to reduce the severity of fatigue during cancer treatment. Psychoeducation and American ginseng may be recommended in adults undergoing cancer treatment. For survivors after completion of treatment, clinicians should recommend exercise, CBT, and mindfulness-based programs; in particular, CBT and mindfulness-based programs have shown efficacy for managing moderate to severe fatigue after treatment. Yoga, acupressure, and moxibustion may also be recommended. Patients at the end of life may be offered CBT and corticosteroids. Clinicians should not recommend L-carnitine, antidepressants, wakefulness agents, or routinely recommend psychostimulants to manage symptoms of CRF. There is insufficient evidence to make recommendations for or against other psychosocial, integrative, or pharmacological interventions for the management of fatigue.Additional information is available at www.asco.org/survivorship-guidelines.

Pilot trial testing the effects of exercise on chemotherapy-induced peripheral neurotoxicity (CIPN) and the interoceptive brain system.

Purpose: Chemotherapy-induced peripheral neurotoxicity (CIPN) is a prevalent, dose-limiting, tough-to-treat toxicity involving numbness, tingling, and pain in the extremities with enigmatic pathophysiology. This randomized controlled pilot study explored the feasibility and preliminary efficacy of exercise during chemotherapy on CIPN and the role of the interoceptive brain system, which processes bodily sensations. Methods: Nineteen patients (65±11 years old, 52% women; cancer type: breast, gastrointestinal, multiple myeloma) starting neurotoxic chemotherapy were randomized to 12 weeks of exercise (home-based, individually tailored, moderate intensity, progressive walking and resistance training) or active control (nutrition education). At pre-, mid-, and post-intervention, we assessed CIPN symptoms (primary clinical outcome: CIPN-20), CIPN signs (tactile sensitivity using monofilaments), and physical function (leg strength). At pre- and post-intervention, we used task-free ("resting") fMRI to assess functional connectivity in the interoceptive brain system, involving the salience and default mode networks. Results: The study was feasible (74-89% complete data across measures) and acceptable (95% retention). We observed moderate/large beneficial effects of exercise on CIPN symptoms (CIPN-20, 0-100 scale: -7.9±5.7, effect size [ES]=-0.9 at mid-intervention; -4.8±7.3, -ES=0.5 at post-intervention), CIPN signs (ES=-1.0 and -0.1), and physical function (ES=0.4 and 0.3). Patients with worse CIPN after neurotoxic chemotherapy had lower functional connectivity within the default mode network (R2=40-60%) and higher functional connectivity within the salience network (R2=20-40%). Exercise tended to increase hypoconnectivity and decrease hyperconnectivity seen in CIPN (R2 = 12%). Conclusion: Exercise during neurotoxic chemotherapy is feasible and may attenuate CIPN symptoms and signs, perhaps via changes in interoceptive brain circuitry. Future work should test for replication with larger samples. ClinicalTrials.gov identifier NCT03021174.

A whole-food, plant-based randomized controlled trial in metastatic breast cancer: weight, cardiometabolic, and hormonal outcomes.

PURPOSE: Breast cancer treatment is associated with weight gain, and obesity and its related cardiometabolic and hormonal risk factors have been associated with poorer outcomes. Dietary intervention may address these risk factors, but limited research has been done in the setting of metastatic breast cancer requiring systemic therapy. METHODS: Women with metastatic breast cancer on stable treatment were randomized 2:1 to an 8-week intervention (n = 21) or control (n = 11). The intervention included weekly assessment visits and an ad libitum whole-food, plant-based (WFPB) diet with provided meals. Cardiometabolic, hormonal, and cancer markers were assessed at baseline, 4 weeks, and 8 weeks. RESULTS: Within the intervention group, mean weight decreased by 6.6% (p < 0.01) after 8 weeks. Fasting insulin decreased from 16.8 uIU/L to 11.2 uIU/L (p < 0.01), concurrent with significantly reduced insulin resistance. Total cholesterol decreased from 193.6 mg/dL to 159 mg/dL (p < 0.01), and low-density lipoprotein (LDL) cholesterol decreased from 104.6 mg/dL to 82.2 mg/dL (p < 0.01). Total testosterone was unchanged, but free testosterone trended lower within the intervention group (p = 0.08) as sex hormone binding globulin increased from 74.3 nmol/L to 98.2 nmol/L (p < 0.01). There were no significant differences in cancer progression markers at week 8, although mean CA 15-3, CA 27.29, and CEA were lower in the intervention group (p = 0.53, p = 0.23, and p = 0.54, respectively) compared to control, when adjusted for baseline. CONCLUSION: WFPB dietary changes during treatment for metastatic breast cancer are well tolerated and significantly improve weight, cardiometabolic and hormonal parameters. Longer studies are warranted to assess the durability of changes. Trial registration First registered at Clinicaltrials.gov (NCT03045289) on February 7, 2017.

High-dose vitamin D to attenuate bone loss in patients with prostate cancer on androgen deprivation therapy: A phase 2 RCT.

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.

A whole food, plant-based randomized controlled trial in metastatic breast cancer: feasibility, nutrient, and patient-reported outcomes.

PURPOSE: Quality of life (QOL) is among the most important outcomes for women with metastatic breast cancer (MBC), and it predicts survival. QOL is negatively impacted by cognitive impairment, fatigue, and weight gain. We assessed whether a whole food, plant-based (WFPB) diet-promoting weight loss is feasible and might improve QOL. METHODS: Women with MBC on stable systemic treatments were randomized 2:1 to 1) WFPB dietary intervention (n = 21) or 2) usual care (n = 11) for 8 weeks. Participants attended weekly education visits and consumed an ad libitum WFPB diet (3 prepared meals/day provided). Patient-reported outcomes and 3-day food records were assessed at baseline and 8 weeks. The effects of WFPB diet on changes in outcomes were assessed by analysis of covariance model controlling for baseline. RESULTS: 20 intervention and 10 control participants completed the trial. Intervention participants were highly adherent to the WFPB diet (94.3 % total calories on-plan). Intervention group nutrient intakes changed significantly including dietary fat (35.8 % to 20.4 % percent calories from fat, p < 0.001) and fiber content (12.7 to 30.8 g fiber/1000 kcal, p < 0.001). Perceived cognitive function (FACT-Cog total + 16.1; 95 % confidence interval [CI] = 0.8-31.7; p = 0.040) and emotional well-being (FACT-B emotional well-being subscale + 2.3; CI = 0.5-4.1; p = 0.016) improved in the WFPB versus the control group. Fatigue, measured by the BFI, improved within the WFPB group for fatigue severity (M = 4.7 ± 2.5[SD] to 3.7 ± 2.3, p = 0.047) and fatigue at its worst (5.8 ± 2.8 to 4.4 ± 2.4, p = 0.011). CONCLUSIONS: Significant dietary changes in this population are feasible and may improve QOL by improving treatment-related symptoms. Additional study is warranted. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03045289. Registered 7 February 2017.

Exercise and inflammatory cytokine regulation among older adults with myeloid malignancies.

Tumor necrosis factor (TNF)α is a major regulator of inflammation. However, the epigenetic regulation of TNFα in the context of an exercise intervention among older adults with cancer is understudied. In this exploratory analysis, we used data from a single-arm mobile health (mHealth) exercise intervention among older adults with myeloid malignancies to 1) assess changes in TNFα promoter methylation, TNFα mRNA expression, serum TNFα and other related-cytokine levels after intervention; and 2) assess correlations between blood markers and exercise levels. Twenty patients were included. From baseline to post-intervention, there was no statistical changes in TNFα promoter methylation status at seven CpG sites, TNFα mRNA expression, and serum TNFα levels. Effect sizes, however, were moderate to large for several CpG sites (-120, -147, -162, and -164; Cohen's d = 0.44-0.75). Median serum TNFα sR1 levels increased (83.63, IQR 130.58, p = 0.06; Cohen's d = 0.18) but not the other cytokines. Increases in average daily steps were correlated with increases in TNFα promoter methylation at CpG sites -147 (r = 0.48; p = 0.06) and -164 (r = 0.51; p = 0.04). Resistance training minutes were negatively correlated with TNFα promoter methylation at CpG site -120 (r = -0.62; p = 0.02). All effect sizes were moderate to large. In conclusion, after a mHealth exercise intervention, we demonstrated changes with moderate to large effect sizes in several CpG sites in the TNFα promoter region. Exercise levels were correlated with increases in TNFα promoter methylation. Larger exercise trials are needed to better evaluate TNFα regulation to inform interventions to augment TNFα regulation in order to improve outcomes in older adults with cancer.

A Whole Food, Plant-Based Randomized Controlled Trial in Metastatic Breast Cancer: Feasibility, Nutrient, and Patient-Reported Outcomes.

Purpose: Quality of life (QOL) is among the most important outcomes for women with metastatic breast cancer (MBC) and it predicts survival. QOL is negatively impacted by cognitive impairment, fatigue, and weight gain. We assessed whether a whole food, plant-based (WFPB) diet promoting weight loss is feasible and might improve QOL. Methods: Women with MBC on stable systemic treatments were randomized 2:1 to 1) WFPB dietary intervention (n = 21) or 2) usual care (n = 11) for 8 weeks. Participants attended weekly education visits and consumed an ad libitum WFPB diet (3 prepared meals/day provided). Patient-reported outcomes and 3-day food records were assessed at baseline and 8 weeks. The effects of WFPB diet on changes in outcomes were assessed by analysis of covariance model controlling for baseline. Results: 20 intervention and 10 control participants completed the trial. Intervention participants were highly adherent to the WFPB diet (94.3% total calories on-plan). Intervention group nutrient intakes changed significantly including dietary fat (35.8-20.4% percent calories from fat, p < 0.001) and fiber content (22.1 to 40.8 grams fiber/1000 kcal, p < 0.001). Perceived cognitive function (FACT-Cog total + 16.1; 95% confidence interval [CI] = 0.8-31.7; p = 0.040) and emotional well-being (FACT-B emotional well-being subscale + 2.3; CI = 0.5-4.1; p = 0.016) improved in the WFPB versus the control group. Fatigue, measured by the BFI, improved within the WFPB group for fatigue severity (M = 4.7 ± 2.5[SD] to 3.7 ± 2.3, p = 0.047) and fatigue at its worst (5.8 ± 2.8 to 4.4 ± 2.4, p = 0.011). Conclusions: Significant dietary changes in this population are feasible and may improve QOL by improving treatment-related symptoms. Additional study is warranted. Trial registration: ClinicalTrials.gov identifier: NCT03045289. Registered 7 February 2017.

Wireless Transcutaneous Electrical Nerve Stimulation (TENS) for Chronic Chemotherapy-Induced Peripheral Neuropathy (CIPN): A Proof-of-Concept Randomized Clinical Trial.

Chemotherapy-induced peripheral neuropathy (CIPN) affects approximately 30 to 60% of people who receive neurotoxic chemotherapy. CIPN is associated with impaired quality of life and function and has few effective treatments. This 6-site, subject and assessor-blinded randomized clinical trial (RCT) was designed to assess 1) preliminary efficacy (ie, alpha pre-specified at .2) of a wearable, app-controlled, transcutaneous electrical nerve stimulation (TENS) device for chronic CIPN and 2) feasibility of conducting a confirmatory trial within the National Cancer Institute Community Oncology Research Program (NCORP) (NCT04367480). The primary outcome was the EORTC-CIPN20. The main secondary outcomes were individual symptoms assessed daily (via 0-10 numeric rating scales). The primary analysis was an analysis of covariance (outcome: EORTC-CIPN20, fixed effect: arm, covariates: baseline EORTC-CIPN20 and site). Secondary analyses used a similar analysis of covariance models (excluding site) for each symptom on subgroups of subjects with ≥4 out of 10 for that symptom at baseline. 142 eligible subjects were randomized and received a device; 130 (91%) completed the study. The difference between groups in the EORCT-CIPN20 at the endpoint (placebo-active) was 1.05 (95% Confidence Interval: -.56, 2.67; P = .199). The difference between groups for the individual symptoms was as follows: hot/burning pain: 1.37 (-.33, 3.08; P = .112), sharp/shooting pain: 1.21 (-.37, 2.79; P = .128), cramping: 1.35 (-.32, 3.02; P = .110), tingling: .23 (-.61, 1.08; P = .587), numbness: .27 (-.51, 1.05; P = .492). An RCT of an app-controlled TENS device for chronic CIPN with excellent retention is feasible in the NCORP. Preliminary efficacy evidence suggests that TENS is promising for pain and cramping from CIPN. A confirmatory RCT of TENS for painful CIPN is highly warranted. PERSPECTIVE: Daily, home-based TENS therapy demonstrates promising efficacy for painful CIPN symptoms in this proof-of-concept randomized clinical trial. Future confirmatory trial is warranted.

A Whole-Food, Plant-Based Randomized Controlled Trial in Metastatic Breast Cancer: Weight, Cardiometabolic, and Hormonal Outcome.

Purpose: Breast cancer treatment is associated with weight gain, and obesity and its related cardiometabolic and hormonal risk factors have been associated with poorer outcomes. Dietary intervention may address these risk factors, but limited research has been done in the setting of metastatic breast cancer requiring systemic therapy. Methods: Women with metastatic breast cancer on stable treatment were randomized 2:1 to an 8-week intervention (n = 21) or control (n = 11). The intervention included weekly assessment visits and an ad libitum whole food, plant-based (WFPB) diet with provided meals. Cardiometabolic, hormonal, and cancer markers were assessed at baseline, 4 weeks, and 8 weeks. Results: Within the intervention group, mean weight decreased by 6.6% (p < 0.01) after 8 weeks. Fasting insulin decreased from 16.8 uIU/L to 11.2 uIU/L (p < 0.01), concurrent with significantly reduced insulin resistance. Total cholesterol decreased from 193.6 mg/dL to 159 mg/dL (p < 0.01) and low-density lipoprotein (LDL) cholesterol decreased from 104.6 mg/dL to 82.2 mg/dL (p < 0.01). Total testosterone was unchanged, but free testosterone trended lower within the intervention group (p = 0.08) as sex hormone binding globulin increased from 74.3 nmol/L to 98.2 nmol/L (p < 0.01). There were no significant differences in cancer progression markers at week 8, although mean CA 15 - 3, CA 27.29, and CEA were lower in the intervention group (p = 0.53, p = 0.23, and p = 0.54, respectively) compared to control, when adjusted for baseline. Conclusion: WFPB dietary changes during treatment for metastatic breast cancer are well tolerated and significantly improve weight and cardiometabolic and hormonal parameters. Longer studies are warranted to assess the durability of changes. Trial registration: First registered at Clinicaltrials.gov (NCT03045289) on February 7, 2017.

Cancer survivorship challenges of rural older adults: a qualitative study.

BACKGROUND: Although research has advanced the field of oncologic geriatrics with survivors to assess their cancer-related needs and devise patient-centered interventions, most of that research has excluded rural populations. This study aimed to understand the survivorship challenges and recommendations in the perspective of rural older adults. METHODS: This was a qualitative study that explored the survivorship challenges and recommendations of rural older adults who have completed curative intent chemotherapy for a solid tumor malignancy in the 12 months prior to enrollment in the present study. RESULTS: Twenty-seven older adult survivors from rural areas completed open-ended semi-structured interviews. The mean age was 73.4 (SD = 5.0). Most participants were non-Hispanic White (96.3%), female (59.3%), married (63.0%), and had up to a high school education (51.9%). Rural older survivors reported a general lack of awareness of survivorship care plans, communication challenges with healthcare team, transportation challenges, financial toxicity, psychological challenges, and diet and physical challenges. Rural older survivors recommend the provision of nutritional advice referral to exercise programs, and social support groups and for their healthcare providers to discuss their survivorship plan with them. CONCLUSIONS: Although study participants reported similar survivorship challenges as urban older adult survivors, additional challenges reported regarding transportation and consideration of farm animals have not been previously reported. Heightened awareness of the survivorship needs of rural older adults may result in better survivorship care for this population.

Information Technology and Telemedicine Services in Community Oncology Practices.

PURPOSE: We described information technology support and use of telemedicine for cancer care and research purposes at community oncology practices within the National Cancer Institute Community Oncology Research Program (NCORP). METHODS: We used data from the NCORP 2017 and 2022 Landscape Assessments. Separate logistic regression models were used to assess factors associated with the use of telemedicine for delivery of cancer care in 2017 and for research purposes in 2022 (cancer care delivery not assessed in 2022). RESULTS: Information was available from 210 and 259 practice groups excluding pediatric-only groups in 2017 and 2022, respectively. In 2017, 30% of practice groups used telemedicine for delivery of cancer care; half of these (15% overall) could use telemedicine for research purposes. In 2022, telemedicine was used for research purposes in 73% of practice groups. In multivariable models, self-identifying as a safety-net hospital was associated with a lower odd of telemedicine use for delivery of cancer care (adjusted odds ratio [AOR], 0.39; 95% CI, 0.17 to 0.93), whereas affiliation with a designated critical access hospital was associated with a higher odd of telemedicine use for delivery of cancer care (AOR, 2.29; 95% CI, 1.10 to 4.76). Having a general survivorship clinic (AOR, 1.92; 95% CI, 1.04 to 3.54) and number of oncology providers (increase per 10 providers; AOR, 1.32; 95% CI, 1.05 to 1.65) were associated with telemedicine use for research purposes. CONCLUSION: Almost one third of NCORP practice groups used telemedicine for cancer care delivery in 2017. In 2022, there is high capacity among NCORP practices (almost three-quarters) to use telemedicine for research purposes, especially among practices with a general survivorship clinic and a greater provider number.

Exercise and epigenetic ages in older adults with myeloid malignancies.

BACKGROUND: Older adults with myeloid malignancies are susceptible to treatment-related toxicities. Accelerated DNAm age, or the difference between DNA methylation (DNAm) age and chronological age, may be used as a biomarker of biological age to predict individuals at risk. In addition, cancer treatment can also lead to accelerated DNAm age. Exercise is a promising intervention to reduce or prevent functional, psychological, and cognitive impairments in older patients with myeloid malignancies, yet there is little evidence of the effects of exercise on DNAm age. We explored (1) the associations of accelerated DNAm age with physical, psychological, and cognitive functions at baseline; (2) changes in DNAm age from baseline to post-intervention; and (3) the associations of changes in accelerated DNAm age with changes in functions from baseline to post-intervention. METHODS: We enrolled older patients with myeloid malignancies to a single-arm pilot study testing a mobile health (mHealth) exercise intervention that combines an exercise program (EXCAP©®) with a mobile application over 2 cycles of chemotherapy (8-12 weeks). Patients completed measures of physical, psychological, and cognitive functions and provided blood samples for analyses of DNAm age at baseline and post-intervention. Paired t-tests or Wilcoxon signed rank tests assessed changes in DNAm ages, and Spearman's correlation assessed the relationships between accelerated ages and functions. RESULTS: We included 20 patients (mean age: 72 years, range 62-80). Accelerated GrimAge, accelerated PhenoAge, and DunedinPACE were stable from baseline to post-intervention. At baseline, DunedinPACE was correlated with worse grip strength (r = -0.41, p = 0.08). From baseline to post-intervention, decreases in accelerated GrimAge (r = -0.50, p = 0.02), accelerated PhenoAge (r = - 0.39, p = 0.09), and DunedinPace (r = - 0.43, p = 0.06) were correlated with increases in distance walked on 6-min walk test. Decreases in accelerated GrimAge (r = - 0.49, p = 0.03), accelerated PhenoAge (r = - 0.40, p = 0.08), and DunedinPace (r = - 0.41, p = 0.07) were correlated with increases in in grip strength. CONCLUSIONS: Among older adults with myeloid malignancies receiving chemotherapy, GrimAge and PhenoAge on average are stable after a mHealth exercise intervention. Decreases in accelerated GrimAge, accelerated PhenoAge, and DunedinPACE over 8-12 weeks of exercise were correlated with increased physical performance. Future trials assessing the effects of exercise on treatment-related toxicities should evaluate DNAm age. Trial registration Clinicaltrials.gov identifier: NCT04981821.

A scalable approach to determine cervical cancer screening needs among emergency department patients in the United States.

The emergency department patient population is disproportionately under-screened for cancer, making it an optimal environment to promote cancer screening among hard-to-reach populations and those without routine access to primary care. The first step in a cancer screening process is identifying screening eligibility (e.g. age, sex) and need (i.e. due or past due). In an effort to support the scalability of an emergency department (ED)-based cervical cancer screening intervention, we examined the performance of a low-resource approach of determining cervical cancer screening needs among ED patients. A convenience sample of ED patients (N = 2807) was randomized to (a) an in-person interview with human subjects research staff or, (b) a self-administered, tablet computer-based survey for determining cervical cancer eligibility and need. Patients were recruited from a high-volume urban ED in Rochester, NY and a low-volume rural ED in Dansville, NY between December 2020 and December 2022. Results of these approaches were compared for equivalence of method for determining adherence status with screening guidelines and under/over-reporting of screening activity. Nearly identical reported rates of non-adherence with screening were identified across conditions (1.7% absolute difference; Χ21 = 0.96, p = 0.33). Our results demonstrate that a low-resource approach of using a tablet-based self-administered survey to determine cervical cancer screening needs is equivalent to a labor intensive in-person interview approach conducted by trained research staff among ED patients.

Cachexia: A systemic consequence of progressive, unresolved disease.

Cachexia, a systemic wasting condition, is considered a late consequence of diseases, including cancer, organ failure, or infections, and contributes to significant morbidity and mortality. The induction process and mechanistic progression of cachexia are incompletely understood. Refocusing academic efforts away from advanced cachexia to the etiology of cachexia may enable discoveries of new therapeutic approaches. Here, we review drivers, mechanisms, organismal predispositions, evidence for multi-organ interaction, model systems, clinical research, trials, and care provision from early onset to late cachexia. Evidence is emerging that distinct inflammatory, metabolic, and neuro-modulatory drivers can initiate processes that ultimately converge on advanced cachexia.

An Unsupervised Machine Learning Approach to Evaluating the Association of Symptom Clusters With Adverse Outcomes Among Older Adults With Advanced Cancer: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Older adults with advanced cancer who have high pretreatment symptom severity often experience adverse events during cancer treatments. Unsupervised machine learning may help stratify patients into different risk groups. Objective: To evaluate whether clusters identified from baseline patient-reported symptom severity were associated with adverse outcomes. Design, Setting, and Participants: This secondary analysis of the Geriatric Assessment Intervention for Reducing Toxicity in Older Patients With Advanced Cancer (GAP70+) Trial (2014-2019) included patients who completed the National Cancer Institute Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) before starting a new cancer treatment regimen and received care at community oncology sites across the United States. An unsupervised machine learning algorithm (k-means with Euclidean distance) clustered patients based on similarities of baseline symptom severities. Clustering variables included severity items of 24 PRO-CTCAE symptoms (range, 0-4; corresponding to none, mild, moderate, severe, and very severe). Total severity score was calculated as the sum of 24 items (range, 0-96). Whether the clusters were associated with unplanned hospitalization, death, and toxic effects was then examined. Analyses were conducted in January and February 2022. Exposures: Symptom severity. Main Outcomes and Measures: Unplanned hospitalization over 3 months (primary), all-cause mortality over 1 year, and any clinician-rated grade 3 to 5 toxic effect over 3 months. Results: Of 718 enrolled patients, 706 completed baseline PRO-CTCAE and were included (mean [SD] age, 77.2 [5.5] years, 401 [56.8%] male patients; 51 [7.2%] Black and 619 [87.8%] non-Hispanic White patients; 245 [34.7%] with gastrointestinal cancer; 175 [24.8%] with lung cancer; mean [SD] impaired Geriatric Assessment domains, 4.5 [1.6]). The algorithm classified 310 (43.9%), 295 (41.8%), and 101 (14.3%) into low-, medium-, and high-severity clusters (within-cluster mean [SD] severity scores: low, 6.3 [3.4]; moderate, 16.6 [4.3]; high, 29.8 [7.8]; P < .001). Controlling for sociodemographic variables, clinical factors, study group, and practice site, compared with patients in the low-severity cluster, those in the moderate-severity cluster were more likely to experience hospitalization (risk ratio, 1.36; 95% CI, 1.01-1.84; P = .046). Moderate- and high-severity clusters were associated with a higher risk of death (moderate: hazard ratio, 1.31; 95% CI, 1.01-1.69; P = .04; high: hazard ratio, 2.00; 95% CI, 1.43-2.78; P < .001), but not toxic effects. Conclusions and Relevance: In this study, unsupervised machine learning partitioned patients into distinct symptom severity clusters; patients with higher pretreatment severity were more likely to experience hospitalization and death. Trial Registration: ClinicalTrials.gov Identifier: NCT02054741.

Effect of Yoga and Mediational Influence of Fatigue on Walking, Physical Activity, and Quality of Life Among Cancer Survivors.

BACKGROUND: Cancer-related fatigue (CRF) negatively affects survivors' walking, engagement in physical activity (PA), and quality of life (QoL). Yoga is an effective therapy for treating CRF; however, evidence from large clinical trials regarding how reducing CRF through yoga influences CRF's interference with survivors' walking, engagement in PA, and QoL is not available. We examined the effects of yoga and the mediational influence of CRF on CRF's interference with walking, PA, and QoL among cancer survivors in a multicenter phase III randomized controlled trial. PATIENTS AND METHODS: Cancer survivors (n=410) with insomnia 2 to 24 months posttreatment were randomized to a 4-week yoga intervention-Yoga for Cancer Survivors (YOCAS)-or standard care. A symptom inventory was used to assess how much CRF interfered with survivors' walking, PA, and QoL. The Multidimensional Fatigue Symptom Inventory-Short Form was used to assess CRF. Two-tailed t tests and analyses of covariance were used to examine within-group and between-group differences. Path analysis was used to evaluate mediational relationships between CRF and changes in CRF's interference with walking, PA, and QoL among survivors. RESULTS: Compared with standard care controls, YOCAS participants reported significant improvements in CRF's interference with walking, PA, and QoL at postintervention (all effect size = -0.33; all P≤.05). Improvements in CRF resulting from yoga accounted for significant proportions of the improvements in walking (44%), PA (53%), and QoL (45%; all P≤.05). CONCLUSIONS: A significant proportion (44%-53%) of the YOCAS effect on CRF's interference with walking, PA, and QoL was due to improvements in CRF among cancer survivors. Yoga should be introduced and included as a treatment option for survivors experiencing fatigue. By reducing fatigue, survivors further improve their walking, engagement in PA, and QoL.

A Novel Use for Pelvic MRI Scans to Estimate Lean Body Mass and Screen for Sarcopenia in Patients With Rectal Cancer.

BACKGROUND: Sarcopenia, the combination of low lean body mass and decreased muscle strength, is associated with significant morbidity and mortality among patients with colorectal cancer. Standard methods for assessing lean body mass and muscle strength, such as bioelectric impedance analysis and handgrip dynamometry, are rarely obtained clinically. Per National Cancer Center Network recommendations, pelvic MRI is routinely collected for staging and surveillance among patients with rectal cancer. However, there are no data assessing the relationship of pelvic MRI lean body mass measurements at the fifth lumbar vertebrae with bioelectric impedance analysis, handgrip strength, or abdominal CT in patients with rectal cancer. Therefore, we aimed to assess whether pelvic MRI lean body mass correlates with a standard for lean body mass measurement (bioelectric impedance analysis), muscle function (handgrip strength), and an imaging modality frequently used in the literature to identify sarcopenia (abdominal CT at the third lumbar vertebrae). IMPACT OF INNOVATION: Lean body mass measurements from routinely collected pelvic MRI at the fifth lumbar vertebrae accurately and reproducibly estimate lean body mass and modestly correlate with handgrip strength. Rectal cancer pelvic MRI may be repurposed for identifying sarcopenia without increasing inconvenience, ionizing radiation exposure, or expenditure to patients with rectal cancer. TECHNOLOGY, MATERIALS, AND METHODS: Patients with locally advanced rectal cancer with pretreatment bioelectric impedance analysis and handgrip strength measurements within 3 months of their staging pelvic MRI were eligible. Axial skeletal muscle areas were segmented using T1-weighted series pelvic MRI at the fifth lumbar vertebrae and abdominal CT at the third lumbar vertebrae using Slice-O-Matic (Tomovision, Montreal, Canada). Lean body mass (kilograms) was derived from skeletal muscle area with standard equations. Handgrip strength (kilograms) was the maximum of 3 dominant hand attempts in the standing anatomical position. The primary outcome was the agreement between lean body mass measured by pelvic MRI (at the fifth lumbar vertebrae) and bioelectric impedance analysis. Secondary outcomes included the concordance of pelvic MRI lean body mass (at the fifth lumbar vertebrae) with abdominal CT (at the third lumbar vertebrae) and handgrip strength. Additionally, the intra- and interobserver validity, internal consistency, and the mean difference (bias) between lean body mass measurements by pelvic MRI and bioelectric impedance analysis were evaluated. PRELIMINARY RESULTS: Sixteen patients were eligible. The average lean body mass was similar and consistent across 2 observers between bioelectric impedance analysis and pelvic MRI. There was a strong correlation between lean body mass measured on pelvic MRI, bioelectric impedance analysis, and abdominal CT. The reliability of 2 pelvic MRI lean body mass measurements (2 weeks apart by blinded observers) and the correlation of lean body mass between pelvic MRI and bioelectric impedance analysis was strong. Inter- and intraobserver correlation, reliability, and internal consistency were strong for the entire cohort. There was a moderate correlation between pelvic MRI lean body mass and handgrip strength. CONCLUSIONS: Lean body mass measured at the fifth lumbar vertebrae on pelvic MRI is reproducible and correlates strongly with measurements from bioelectric impedance analysis (standard) and abdominal CT at the third lumbar vertebrae and modestly with handgrip strength. These data suggest that MRI lean body mass measurements may be a method to screen patients with rectal cancer for sarcopenia. FUTURE DIRECTIONS: Future studies may evaluate changes in lean body mass on serial pelvic MRI studies among patients with rectal cancer.

Low Preoperative Serum Creatinine is Common and Associated With Poor Outcomes After Nonemergent Inpatient Surgery.

OBJECTIVE: To assess the association between low preoperative serum creatinine and postoperative outcomes. BACKGROUND: The association between low creatinine and poor surgical outcomes is not well understood. METHODS: We identified patients with creatinine in the 7 days preceding nonemergent inpatient surgery in the American College of Surgeons National Surgical Quality Improvement Program database from 2005 to 2020. Multivariable logistic regression was used to examine the association between creatinine and 30-day mortality and major complications. RESULTS: Of 1,809,576 patients, 27.8% of males and 23.5% of females had low preoperative serum creatinine, 14.6% experienced complications, and 1.2% died. For males, compared with the reference creatinine of 0.85 to 1.04, those with serum creatinine ≤0.44 had 55% increased odds of mortality [ adjusted odds ratio (aOR), 1.55; 95% CI, 1.29-1.86] and 82% increased odds of major complications (aOR, 1.82; 95% CI, 1.69-1.97). Similarly, for females, compared with the reference range of 0.65 to 0.84, those with serum creatinine ≤0.44 had 49% increased odds of mortality (aOR, 1.49; 95% CI, 1.32-1.67) and 76% increased odds of major complications (aOR, 1.76; 95% CI, 1.70-1.83). These associations persisted for the total cohort, among those with mildly low albumin, and for those with creatinine values measured 8 to 30 days preoperatively. CONCLUSIONS: A low preoperative creatinine is common and associated with poor outcomes after nonemergent inpatient surgery. A low creatinine may help identify high-risk patients who may benefit from further evaluation and optimization.