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.

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.

Association of polypharmacy and potential drug-drug interactions with adverse treatment outcomes in older adults with advanced cancer.

BACKGROUND: Polypharmacy is common in older adults who are starting cancer treatment and is associated with an increased risk of potentially inappropriate medications (PIMs) and potential drug-drug interactions (PDIs). The authors evaluated the association of medication measures with adverse outcomes in older adults with advanced cancer who were receiving systemic therapy. METHODS: This secondary analysis from GAP 70+ Trial (ClinicalTrials.gov identifier NCT02054741; principal investigator, Supriya G. Mohile) enrolled patients aged 70 years and older with advanced cancer who planned to start a new treatment regimen (n = 718). Polypharmacy was assessed before the initiation of treatment and was defined as the concurrent use of eight or more medications. PIMs were categorized using 2019 Beers Criteria and the Screening Tool of Older Persons' Prescriptions. PDIs were evaluated using Lexi-Interact Online. Study outcomes were assessed within 3 months of treatment and included: (1) the number of grade ≥2 and ≥3 toxicities according to the National Cancer Institute Common Toxicity Criteria, (2) treatment-related unplanned hospitalization, and (3) early treatment discontinuation. Multivariable regression models examined the association of medication measures with outcomes. RESULTS: The mean patient age was 77 years, and 57% had lung or gastrointestinal cancers. The median number of medications was five (range, 0-24 medications), 28% of patients received eight or more medications, 67% received one or more PIM, and 25% had one or more major PDI. The mean number of grade ≥2 toxicities in patients with polypharmacy was 9.8 versus 7.7 in those without polypharmacy (adjusted ß = 1.87; standard error, 0.71; p <.01). The mean number of grade ≥3 toxicities in patients with polypharmacy was 2.9 versus 2.2 in patients without polypharmacy (adjusted ß = 0.59; standard error, 0.29; p = .04). Patients with who had one or more major PDI had 59% higher odds of early treatment discontinuation (odds ratio, 1.59; 95% confidence interval, 1.03-2.46; p = .03). CONCLUSIONS: In a cohort of older adults with advanced cancer, polypharmacy and PDIs were associated with an increased risk of adverse treatment outcomes. Providing meaningful screening and interventional tools to optimize medication use may improve treatment-related outcomes in these patients.

External Validation of Risk Factors for Unplanned Hospitalization in Older Adults With Advanced Cancer Receiving Chemotherapy.

BACKGROUND: Older adults (age ≥65 years) receiving chemotherapy are at risk for hospitalization. Predictors of unplanned hospitalization among older adults receiving chemotherapy for cancer were recently published using data from a study conducted by the Cancer and Aging Research Group (CARG). Our study aimed to externally validate these predictors in an independent cohort including older adults with advanced cancer receiving chemotherapy. METHODS: This validation cohort included patients (n=369) from the GAP70+ trial usual care arm. Enrolled patients were aged ≥70 years with incurable cancer and were starting a new line of chemotherapy. Previously identified risk factors proposed by the CARG study were ≥3 comorbidities, albumin level <3.5 g/dL, creatinine clearance <60 mL/min, gastrointestinal cancer, ≥5 medications, requiring assistance with activities of daily activities (ADLs), and having someone available to take them to the doctor (ie, presence of social support). The primary outcome was unplanned hospitalization within 3 months of treatment initiation. Multivariable logistic regression was applied including the 7 identified risk factors. Discriminative ability of the fitted model was performed by calculating the area under the receiver operating characteristic (AUC) curve. RESULTS: Mean age of the cohort was 77 years, 45% of patients were women, and 29% experienced unplanned hospitalization within the first 3 months of treatment. The proportions of hospitalized patients with 0-3, 4-5, and 6-7 identified risk factors were 24%, 28%, and 47%, respectively (P=.04). Impaired ADLs (odds ratio, 1.76; 95% CI, 1.04-2.99) and albumin level <3.5 g/dL (odds ratio, 2.23; 95% CI, 1.37-3.62) were significantly associated with increased odds of unplanned hospitalization. The AUC of the model, including the 7 identified risk factors, was 0.65 (95% CI, 0.59-0.71). CONCLUSIONS: The presence of a higher number of risk factors was associated with increased odds of unplanned hospitalization. This association was largely driven by impairment in ADLs and low albumin level. Validated predictors of unplanned hospitalization can help with counseling and shared decision-making with patients and their caregivers. CLINICALTRIALS: gov identifier: NCT02054741.

Evaluating the association of frailty with communication about aging-related concerns between older patients with advanced cancer and their oncologists.

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.

Evaluation of geriatric assessment and management on the toxic effects of cancer treatment (GAP70+): a cluster-randomised study.

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.

The shared uncertainty experience of older adults with advanced cancer and their caregivers.

OBJECTIVE: One primary source of psychological distress in patients with cancer and their caregivers is uncertainty. However, the uncertainty trajectory and its relationship between older adults with advanced cancer and their caregivers have rarely been examined. This study describes the uncertainty trajectory in patient-caregiver dyads, explores the effect of geriatric assessment (GA) intervention on trajectory, and examines the interdependent relationship of uncertainty. METHODS: This secondary analysis used longitudinal data from a national cluster-randomized controlled trial examining a GA intervention compared to usual care. Participants completed the modified 9-item Mishel Uncertainty in Illness Scale at enrollment, 4-6 weeks, 3 months, and 6 months. The dyadic growth model and cross-lagged actor-partner interdependence model were used. RESULTS: A total of 397 dyads (patient age M = 76.81 ± SD5.43; caregiver age M = 66.69 ± SD12.52) were included. Both had a trend of decreased uncertainty over time (b = -0.16, p < 0.01). There was a greater decrease in uncertainty among caregivers in the GA group than those in the usual care group (b = -0.46, p = 0.02). For both patients and caregivers, their past uncertainty was a significant predictor of their own current uncertainty (i.e., actor effect, p < 0.01). The individual's past uncertainty was a significant predictor of the other dyad member's current uncertainty (i.e., partner effect, p < 0.05), indicating an interdependent relationship between patient and caregiver uncertainty over time. CONCLUSIONS: Findings suggest patient and caregiver function as a unit with uncertainty levels affecting each other. Future interventions could build on GA to address uncertainty for older patients with advanced cancer and caregivers.

The association between cancer-related fatigue and diabetes from pre-chemotherapy to 6 months post-chemotherapy.

PURPOSE: To quantify the relationship between diabetes and fatigue from pre-chemotherapy to 6 months post-chemotherapy for women with breast cancer compared to women without a history of cancer (controls). METHODS: This was a secondary analysis from a nationwide prospective longitudinal study of female patients with breast cancer undergoing chemotherapy and controls. Diabetes diagnosis (yes/no) was obtained at baseline, and cancer-related fatigue was measured using the Multidimensional Fatigue Symptom Inventory (MFSI) pre-, post-, and 6 months post-chemotherapy in patients; controls were assessed at equivalent time points. Repeated measures mixed effects models estimated the association between fatigue and diabetes controlling for cancer (yes/no), body mass index, exercise and smoking habits, baseline anxiety and depressive symptoms, menopausal status, marital status, race, and education. RESULTS: Among 439 patients and 235 controls (52.8 ± 10.5 years old), diabetes was twice as prevalent among patients as controls (11.6% vs. 6.8%). At baseline, diabetes was associated with worse fatigue (4.1 ± 1.7 points, p = 0.017). Also, diabetes was associated with clinically meaningful worse fatigue throughout the study period among all participants (5.2 ± 1.9 points, p = 0.008) and patients alone (4.5 ± 2.0, p = 0.023). For the MFSI subdomains among patients, diabetes was associated with worse general (p = 0.005) and mental fatigue (p = 0.026). CONCLUSIONS: Diabetes was twice as prevalent in women with breast cancer compared to controls, and diabetes was associated with more severe cancer-related fatigue in patients before and after chemotherapy and at 6 months post-chemotherapy. Interventions that address diabetes management may also help address cancer-related fatigue during chemotherapy treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01382082, first posted June 27, 2011.

Exploratory Analysis of Associations Between Whole Blood Mitochondrial Gene Expression and Cancer-Related Fatigue Among Breast Cancer Survivors.

BACKGROUND: Cancer-related fatigue is a prevalent, debilitating, and persistent condition. Mitochondrial dysfunction is a putative contributor to cancer-related fatigue, but relationships between mitochondrial function and cancer-related fatigue are not well understood. OBJECTIVES: We investigated the relationships between mitochondrial DNA (mtDNA) gene expression and cancer-related fatigue, as well as the effects of fish and soybean oil supplementation on these relationships. METHODS: A secondary analysis was performed on data from a randomized controlled trial of breast cancer survivors 4-36 months posttreatment with moderate-severe cancer-related fatigue. Participants were randomized to take 6 g fish oil, 6 g soybean oil, or 3 g each daily for 6 weeks. At pre- and postintervention, participants completed the Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire and provided whole blood for assessment of mtDNA gene expression. The expression of 12 protein-encoding genes was reduced to a single dimension using principal component analysis for use in regression analysis. Relationships between mtDNA expression and cancer-related fatigue were assessed using linear regression. RESULTS: Among 68 participants, cancer-related fatigue improved and expression of all mtDNA genes decreased over 6 weeks with no effect of treatment group on either outcome. Participants with lower baseline mtDNA gene expression had greater improvements in cancer-related fatigue. No significant associations were observed between mtDNA gene expression and cancer-related fatigue at baseline or changes in mtDNA gene expression and changes in cancer-related fatigue. DISCUSSION: Data from this exploratory study add to the growing literature that mitochondrial dysfunction may contribute to the etiology and pathophysiology of cancer-related fatigue.

The longitudinal relationship between immune cell profiles and frailty in patients with breast cancer receiving chemotherapy.

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 (ß = 0.04; p < 0.05), neutrophils (ß = 0.04; p < 0.05), and NLR (ß = 0.04; p < 0.01). From T1 to T2, a greater increase in cellular markers of inflammation was associated with frailty at T2 (WBC: ß = 0.02, p < 0.05; neutrophils: ß = 0.03, p < 0.05; NLR: ß = 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.

Patient and caregiver agreement on prognosis estimates for older adults with advanced cancer.

BACKGROUND: Disagreements between patients and caregivers about treatment benefits, care decisions, and patients' health are associated with increased patient depression as well as increased caregiver anxiety, distress, depression, and burden. Understanding the factors associated with disagreement may inform interventions to improve the aforementioned outcomes. METHODS: For this analysis, baseline data were obtained from a cluster-randomized geriatric assessment trial that recruited patients aged ≥70 years who had incurable cancer from community oncology practices (University of Rochester Cancer Center 13070; Supriya G. Mohile, principal investigator). Patient and caregiver dyads were asked to estimate the patient's prognosis. Response options were 0 to 6 months, 7 to 12 months, 1 to 2 years, 2 to 5 years, and >5 years. The dependent variable was categorized as exact agreement (reference), patient-reported longer estimate, or caregiver-reported longer estimate. The authors used generalized estimating equations with multinomial distribution to examine the factors associated with patient-caregiver prognostic estimates. Independent variables were selected using the purposeful selection method. RESULTS: Among 354 dyads (89% of screened patients were enrolled), 26% and 22% of patients and caregivers, respectively, reported a longer estimate. Compared with dyads that were in agreement, patients were more likely to report a longer estimate when they screened positive for polypharmacy (ß = 0.81; P = .001), and caregivers reported greater distress (ß = 0.12; P = .03). Compared with dyads that were in agreement, caregivers were more likely to report a longer estimate when patients screened positive for polypharmacy (ß = 0.82; P = .005) and had lower perceived self-efficacy in interacting with physicians (ß = -0.10; P = .008). CONCLUSIONS: Several patient and caregiver factors were associated with patient-caregiver disagreement about prognostic estimates. Future studies should examine the effects of prognostic disagreement on patient and caregiver outcomes.

Association Between Caregiver-Oncologist Discordance in Patient's Life Expectancy Estimates and Caregiver Perceived Autonomy Support by the Oncologist.

BACKGROUND: Caregiver perceived autonomy support by the oncologist is important for caregiver well-being and may be affected by the patient's survival. We determined the association of caregiver-oncologist discordance in patient's life expectancy estimates with perceived autonomy support over time and whether the association differed by patient survival status. MATERIALS AND METHODS: We used data from a geriatric assessment cluster-randomized trial (URCC 13070) that recruited patients aged at least 70 years with incurable cancer considering or receiving treatment, their caregivers, and their oncologists. At baseline, caregivers and oncologists were asked to estimate patient's life expectancy (0-6 months, 7-12 months, 1-2 years, 2-5 years, and >5 years; any difference in response was considered discordant). At 4-6 weeks, 3 months, and 6 months, caregivers completed the Health Care Climate Questionnaire (HCCQ), which measured perceived autonomy support by the oncologist. Generalized estimating equation modeling was conducted to assess the association of baseline caregiver-oncologist discordance with longitudinal HCCQ scores, stratified by patient 6-month survival status. RESULTS: Discordant life expectancy estimates were present in 72.0% of dyads. In multivariate analyses, caregiver-oncologist discordance in patient's life expectancy estimates was associated with higher caregiver HCCQ scores. In stratified analysis, caregiver-oncologist discordance was associated with lower caregiver HCCQ scores (ß = -3.46; 95% CI, -4.64 to -2.29) among patients who died within 6 months but with higher caregiver HCCQ scores (ß = 1.33; 95% CI, 0.63-2.04) among patients who survived beyond 6 months. CONCLUSION: Interventions aimed at mitigating discordance need to consider its association with caregiver perceived autonomy support and patient's survival in order to better inform caregiver expectations. IMPLICATIONS FOR PRACTICE: Among patients who died within the first 6 months, caregivers who estimated a different length of life for the patient compared with oncologists were more likely to report lower support from the oncologist, whereas the opposite relationship was seen within patients who survived beyond the first 6 months. When designing interventions to improve caregiver understanding of the patient's prognosis, its relationship with caregiver-perceived support and patient's survival needs to be considered.

The Relationship Between Frailty and Emotional Health in Older Patients with Advanced Cancer.

BACKGROUND: Aging-related deficits that eventually manifest as frailty may be associated with poor emotional health in older patients with advanced cancer. This study aimed to examine the relationship between frailty and emotional health in this population. METHODS: This was a secondary analysis of baseline data from a nationwide cluster randomized trial. Patients were aged ≥70 years with incurable stage III/IV solid tumors or lymphomas, had ≥1 geriatric assessment (GA) domain impairment, and had completed the Geriatric Depression Scale, Generalized Anxiety Disorder-7, and Distress Thermometer. Frailty was assessed using a Deficit Accumulation Index (DAI; range 0-1) based on GA, which did not include emotional health variables (depression and anxiety), and participants were stratified into robust, prefrail, and frail categories. Multivariate logistic regression models examined the association of frailty with emotional health outcomes. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were reported. RESULTS: Five hundred forty-one patients were included (mean age: 77 years; 70-96). DAI ranged from 0.04 to 0.94; 27% of patients were classified as robust, 42% prefrail, and 31% frail. Compared with robust patients, frail patients had an increased risk of screening positive for depression (aOR = 12.8; 95% CI = 6.1-27.0), anxiety (aOR = 6.6; 95% CI = 2.2-19.7), and emotional distress (aOR = 4.62; 95% CI = 2.9-8.3). Prefrail compared with robust patients also had an increased risk of screening positive for depression (aOR = 2.22; 95% CI = 1.0-4.8) and distress (aOR = 1.71; 95% CI = 1.0-2.8). CONCLUSION: In older patients with advanced cancer, frailty is associated with poorer emotional health, which indicates a need for an integrated care approach to treating these patients. IMPLICATIONS FOR PRACTICE: A relationship exists between frailty and poor emotional health in older adults with advanced cancer. Identifying areas of frailty can prompt screening for emotional health and guide delivery of appropriate interventions. Alternatively, attention to emotional health may also improve frailty.

Caregiver-Oncologist Prognostic Concordance, Caregiver Mastery, and Caregiver Psychological Health and Quality of Life.

BACKGROUND: Caregivers of adults with cancer often report a different understanding of the patient's prognosis than the oncologist. We examine the associations of caregiver-oncologist prognostic concordance with caregiver depressive symptoms, distress, and quality of life (QoL). We also explore whether these relationships differed by caregiver environment mastery, an individual's sense of control, and effectiveness in managing life situations. MATERIALS AND METHODS: We used data from a national geriatric assessment cluster-randomized trial (URCC 13070) that recruited patients aged 70 years and older with incurable cancer considering any line of cancer treatment at community oncology practices, their caregivers, and their oncologists. At enrollment, caregivers and oncologists estimated the patient's prognosis (0-6 months, 7-12 months, 1-2 years, 2-5 years, and >5 years; identical responses were concordant). Caregivers completed the Ryff's environmental mastery at enrollment. At 4-6 weeks, caregivers completed the Patient Health Questionnaire-2 (depressive symptoms), distress thermometer, and 12-Item Short-Form Health Survey (quality of life [QoL]). We used generalized estimating equations in models adjusted for covariates. We then assessed the moderation effect of caregiver mastery. RESULTS: Of 411 caregiver-oncologist dyads (mean age = 66.5 years), 369 provided responses and 28% were concordant. Prognostic concordance was associated with greater caregiver depressive symptoms (ß = 0.30; p = .04) but not distress or QoL. A significant moderation effect for caregiver depressive symptoms was found between concordance and mastery (p = .01). Specifically, among caregivers with low mastery (below median), concordance was associated with greater depressive symptoms (ß = 0.68; p = .003). CONCLUSIONS: Caregiver-oncologist prognostic concordance was associated with caregiver depressive symptoms. We found a novel moderating effect of caregiver mastery on the relationship between concordance and caregiver depressive symptoms. IMPLICATIONS FOR PRACTICE: Caregiver-oncologist prognostic concordance is associated with greater caregiver depressive symptoms, particularly in those with low caregiver mastery. When discussing prognosis with caregivers, physicians should be aware that prognostic understanding may affect caregiver psychological health and should assess their depressive symptoms. In addition, while promoting accurate prognostic understanding, physicians should also identify strengths and build resilience among caregivers.

Longitudinal study of inflammatory, behavioral, clinical, and psychosocial risk factors for chemotherapy-induced peripheral neuropathy.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect of taxane and platinum chemotherapy for breast cancer. Clinicians cannot accurately predict CIPN severity partly because its pathophysiology is poorly understood. Although inflammation may play a role in CIPN, there are limited human studies. Here, we identified the strongest predictors of CIPN using variables measured before taxane- or platinum-based chemotherapy, including serum inflammatory markers. METHODS: 116 sedentary women with breast cancer (mean age 55 years) rated (1) numbness and tingling and (2) hot/coldness in hands/feet on 0-10 scales before and after 6 weeks of taxane- or platinum-based chemotherapy. A sub-study was added to collect cytokine data in the final 55 patients. We examined all linear models to predict CIPN severity at 6 weeks using pre-chemotherapy assessments of inflammatory, behavioral, clinical, and psychosocial factors. The final model was selected via goodness of fit. RESULTS: The strongest pre-chemotherapy predictors of numbness and tingling were worse fatigue/anxiety/depression (explaining 27% of variance), older age (9%), and baseline neuropathy (5%). The strongest predictors of hot/coldness in hands/feet were worse baseline neuropathy (11%) and fatigue/anxiety/depression (6%). Inflammation was a risk for CIPN, per more pro-inflammatory IFN-γ (12%) and IL-1ß (6%) and less anti-inflammatory IL-10 (6%) predicting numbness/tingling and more IFN-γ (17%) and less IL-10 (9%) predicting hot/coldness in hands/feet. CONCLUSIONS: The strongest pre-chemotherapy predictors of CIPN included worse fatigue/anxiety/depression and baseline neuropathy. A pro-inflammatory state also predicted CIPN. Because this is an exploratory study, these results suggest specific outcomes (e.g., IL-1ß) and effect size estimates for designing replication and extension studies. CLINICAL TRIAL REGISTRATION: NCT00924651.

Effects of High-Dose Vitamin D Supplementation on Phase Angle and Physical Function in Patients with Prostate Cancer on ADT.

PURPOSE: Androgen deprivation therapy (ADT) is commonly used to treat patients with advanced prostate cancer but is associated with functional decline. Bioelectrical impedance analysis (BIA)-derived phase angle may reflect frailty and functional decline in cancer patients. High-dose vitamin D supplementation may improve phase angle values and physical function. METHODS: We conducted an exploratory analysis from a phase II randomized controlled trial investigating the efficacy of high-dose vitamin D supplementation in prostate cancer patients (age ≥ 60 yrs). Fifty-nine patients were randomized to high-dose vitamin D (600 IU/day plus 50,000 IU/week) or low-dose: RDA for vitamin D (600 IU/day plus placebo weekly) for 24 weeks. Phase angle was measured by BIA. Physical function measures included handgrip strength, 6-minute walk test, Short Performance Physical Battery and leg extension. All testing was completed at baseline, week 12 and week 24. RESULTS: Phase angle values were wider over the entire study in the high-dose vitamin D arm indicating healthier muscle cells. The low-dose vitamin D arm had phase angle values consistent with frailty cutoffs in older men (<5.7°). CONCLUSION: Patients in the high-dose vitamin D arm experienced wider phase angle values over the course of the study which may indicate less frailty. ClinicalTrials.gov ID: NCT02064946.

Excess Body Weight and Cancer-Related Fatigue, Systemic Inflammation, and Serum Lipids in Breast Cancer Survivors.

BACKGROUND: Cancer-related fatigue (CRF) is a common side effect impacting breast cancer survivors. Research points to a relationship between obesity and CRF in breast cancer survivors related to elevated systemic inflammation and metabolic alterations. METHODS: This cross-sectional study examined the relationship of obesity to CRF, inflammatory markers and serum lipids through a secondary analysis of a nationwide randomized controlled trial. Breast cancer survivors with CRF were categorized based on BMI category. Symptoms of CRF, inflammatory markers and serum fatty acids were assessed among groups. RESULTS: There were 105 breast cancer survivors in the analysis. BMI was positively associated with CRF based on MFSI General (p = 0.020; 95% C.I. 0.024, 0.273) and MFSI Physical (p = 0.013; 95% C.I. 0.035, 0.298) subscales. TNF-α (p = 0.007; 95% C.I. 0.007, 0.044), and IL-6 (p = 0.020; 95% C.I. 0.006, 0.073) were elevated in the obese. Monounsaturated fatty acid levels (p = 0.047; 95% C.I. 0.000, 0.053) and the omega-6 to omega-3 fatty acid ratio were associated with obesity (p = 0.047; 95% C.I. 0.002, 0.322). CONCLUSIONS: Obese breast cancer survivors had greater levels of CRF, inflammatory markers and certain fatty acids. Inflammatory markers and fatty acids were not found to have any mediating or positive association with CRF variables in this analysis. NCT02352779.

Association of Polypharmacy and Potentially Inappropriate Medications With Physical Functional Impairments in Older Adults With Cancer.

BACKGROUND: Polypharmacy and potentially inappropriate medications (PIMs) are prevalent in older adults with cancer, but their associations with physical function are not often studied. This study examined the associations of polypharmacy and PIMs with physical function in older adults with cancer, and determined the optimal cutoff value for the number of medications most strongly associated with physical functional impairment. METHODS: This cross-sectional analysis used baseline data from a randomized study enrolling patients aged ≥70 years with advanced cancer starting a new systemic cancer treatment. We categorized PIM using 2015 American Geriatrics Society Beers Criteria. Three validated physical function measures were used to assess patient-reported impairments: activities of daily living (ADL) scale, instrumental activities of daily living (IADL) scale, and the Older Americans Resources and Services Physical Health (OARS PH) survey. Optimal cutoff value for number of medications was determined by the Youden index. Separate multivariate logistic regressions were then performed to examine associations of polypharmacy and PIMs with physical function measures. RESULTS: Among 439 patients (mean age, 76.9 years), the Youden index identified ≥8 medications as the optimal cutoff value for polypharmacy; 43% were taking ≥8 medications and 62% were taking ≥1 PIMs. On multivariate analysis, taking ≥8 medications was associated with impairment in ADL (adjusted odds ratio [aOR], 1.64; 95% CI, 1.01-2.58) and OARS PH (aOR, 1.73; 95% CI, 1.01-2.98). PIMs were associated with impairments in IADL (aOR, 1.72; 95% CI, 1.09-2.73) and OARS PH (aOR, 1.97; 95% CI, 1.15-3.37). A cutoff of 5 medications was not associated with any of the physical function measures. CONCLUSIONS: Physical function, an important component of outcomes for older adults with cancer, is cross-sectionally associated with polypharmacy (defined as ≥8 medications) and with PIMs. Future studies should evaluate the association of polypharmacy with functional outcomes in this population in a longitudinal fashion.

Longitudinal assessment of the impact of higher body mass index on cancer-related fatigue in patients with breast cancer receiving chemotherapy.

PURPOSE: To assess the impact of obesity on cancer-related fatigue (CRF) in patients with breast cancer, through a secondary analysis of a large, longitudinal, nationwide study of breast cancer patients beginning chemotherapy. METHODS: All patients (N = 565; aged 53 ± 10.6) with breast cancer completed the multidimensional fatigue symptom inventory and the symptom inventory to measure CRF symptoms at baseline, post-chemotherapy, and 6 months post-chemotherapy. Height and weight at baseline were used to categorize subjects based on body mass index (BMI): obese (≥ 30.0 kg/m2; n = 294), overweight (25.0-29.9 kg/m2; n = 146), and normal weight (18.5-24.9 kg/m2; n = 125). Multivariate regression models evaluated the relationship of obesity level to CRF over time, controlling for age, menopausal status, race, Karnofsky Performance Status, cancer stage, radiation, and exercise status. RESULTS: At baseline, the obese had significantly higher CRF symptoms than the normal weight subjects for both the Multidimensional fatigue symptom inventory (MFSI) total (obese = 11.2 vs normal weight = 6.3; p = 0.03) and Symptom Inventory (SI) (obese = 3.5 vs normal weight = 2.9; p = 0.03). Significantly higher SI fatigue scores persisted at post-chemotherapy for the obese (obese = 5.0 vs normal weight = 4.4; p = 0.02). At 6 months post-chemotherapy, the obese patients still had significantly higher SI fatigue scores (obese = 3.5 vs normal weight = 3.0; p = 0.05). CONCLUSION: Obese patients suffered greater CRF from pre-chemotherapy through 6 months post-chemotherapy. Recommendations for weight loss or weight maintenance may impact CRF levels in obese breast cancer patients before and after chemotherapy.