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.

Barriers and Facilitators to Adherence to a Mediterranean Diet Intervention during Chemotherapy Treatment: A Qualitative Analysis.

Patients undergoing chemotherapy are at risk for malnutrition and a high symptom burden, and nutritional interventions can address clinical and supportive care outcomes. Herein, we identified barriers and facilitators to adhering to a Mediterranean Diet (MedDiet) intervention during chemotherapy. Patients with cancer (any type) who were undergoing chemotherapy were enrolled into a clinical trial testing the effects of an 8-week MedDiet intervention on cancer-related fatigue. Participants were randomized 2:1, MedDiet:control. The intervention entailed food provision, education, a cookbook, a session with a nutritionist, and weekly check-ins. Post-intervention, all participants completed semi-structured exit interviews. The interviews were transcribed and open coding was conducted to describe the facilitators and barriers to MedDiet adherence. Participants (n = 29, n = 21 in the intervention group) were 51.0 ± 15.1 years old and 93.1% had breast cancer. Educational materials and convenient food delivery were the highest reported facilitators. Many patients offered that changing their diet gave a sense of control and empowerment. Barriers to adherence were that the frozen food was unappetizing, participants' (or their spouse/children's) food preferences did not align with the MedDiet, and chemotherapy-induced side effects that prevented food consumption (eg, mouth sores, lack of appetite). This project helps understand the patient experience within nutritional interventions to optimize dietary programs during chemotherapy treatment.

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.

Cardiometabolic health impacts of time-restricted eating: implications for type 2 diabetes, cancer and cardiovascular diseases.

PURPOSE OF REVIEW: Time-restricted eating (TRE) entails consuming energy intake within a 4- to 10-h window, with the remaining time spent fasting. Although studies have reported health benefits from TRE, little is known about the impact of TRE on common chronic diseases such as type 2 diabetes, cancer and cardiovascular disease. This review summarizes and critically evaluates the most recent TRE research findings relevant to managing and treating these chronic diseases. RECENT FINDINGS: Most recent TRE studies have been in populations with overweight/obesity or metabolic syndrome; two have been in populations with diabetes, three in cancer survivors and none in populations with cardiovascular disease. Collectively, these studies showed that participants could adhere to TRE and TRE is well tolerated. These studies also showed preliminary efficacy for improved glucose regulation and insulin sensitivity, a reduction in body fat and blood pressure, reduced cardiovascular risk scores and increased quality of life. More research is required to define the most effective TRE protocol (i.e. length and timing of eating window, intervention duration). SUMMARY: TRE has demonstrated benefits on cardiovascular, metabolic and clinical outcomes relevant to the underlying pathophysiology, but there are limited data on TRE implemented specifically within populations with diabetes, cancer or cardiovascular disease.

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.

Fatigue, anxiety, and quality of life in breast cancer patients compared to non-cancer controls: a nationwide longitudinal analysis.

PURPOSE: Fatigue and anxiety are common and significant symptoms reported by cancer patients. Few studies have examined the trajectory of multidimensional fatigue and anxiety, the relationships between them and with quality of life. METHODS: Breast cancer patients (n = 580) from community oncology clinics and age-matched controls (n = 364) completed fatigue and anxiety questionnaires prior to chemotherapy (A1), at chemotherapy completion (A2), and six months post-chemotherapy (A3). Linear mixed models (LMM) compared trajectories of fatigue /anxiety over time in patients and controls and estimated their relationship with quality of life. Models adjusted for age, education, race, BMI, marital status, menopausal status, and sleep symptoms. RESULTS: Patients reported greater fatigue and anxiety compared to controls at all time points (p's < 0.001, 35% clinically meaningful anxiety at baseline). From A1 to A2 patients experienced a significant increase in fatigue (ß = 8.3 95%CI 6.6,10.0) which returned to A1 values at A3 but remained greater than controls' (p < 0.001). General, mental, and physical fatigue subscales increased from A1 to A2 remaining significantly higher than A1 at A3 (p < 0.001). Anxiety improved over time (A1 to A3 ß = - 4.3 95%CI -2.6,-3.3) but remained higher than controls at A3 (p < 0.001). Among patients, fatigue and anxiety significantly predicted one another and quality of life. Menopausal status, higher BMI, mastectomy, and sleep problems also significantly predicted change in fatigue. CONCLUSION: Breast cancer patients experience significant fatigue and anxiety up to six months post-chemotherapy that is associated with worse quality of life. Future interventions should simultaneously address anxiety and fatigue, focusing on mental and physical fatigue subdomains.

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.

Chemotherapy-induced peripheral neuropathy (CIPN) and its treatment: an NIH Collaboratory study of claims data.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a disabling complication of many chemotherapies. We investigated the feasibility of using health plan claims and administrative data to identify CIPN occurrence by comparing patients who received neurotoxic and non-neurotoxic chemotherapies. METHODS: The sample included over 53,000,000 patients from two regional and one national insurer in the USA (> 400,000 exposed to chemotherapy). Peripheral neuropathy was identified using a broad definition (definition 1) and a specific definition (i.e., drug-induced polyneuropathy code) (definition 2). RESULTS: CIPN incidence as measured by definition 1 within 6 months of chemotherapy initiation was 18.1% and 6.2% for patients who received neurotoxic and non-neurotoxic chemotherapy, respectively (relative risk neurotoxic vs. non-neurotoxic (RR), 2.93 (95% CI, 2.87-2.98)). For definition 2, these incidences were 3.6% and 0.1% (RR, 25.2 (95% CI, 22.8-27.8)). The incidences of new analgesic prescriptions for neurotoxic and non-neurotoxic groups were as follows: gabapentin, 7.1%/1.7%; pregabalin, 0.69%/0.31%; and duloxetine, 0.78%/0.76%. The incidence of CIPN as defined by definitions 1 and 2 was low compared with that of published research studies, but the relative risk of CIPN among patients who received neurotoxic chemotherapies compared with those who received non-neurotoxic chemotherapies was high using definition 2. CONCLUSIONS: These data suggest that as used currently by clinicians, administrative codes likely underestimate CIPN incidence. Thus, studies using administrative data to estimate CIPN incidence are not currently feasible. However, the drug-induced polyneuropathy code is a specific indicator of CIPN in administrative data and may be useful for investigating predictors or potentially preventive therapies of CIPN.

The Patient-Provider Relationship: Predictors of black/African American Cancer Patients' Perceived Quality of Care and Health Outcomes.

We examined whether the patient-provider relationship (PPR) is associated with Black survivors' health outcomes and whether this association was mediated by the quality of care. The outcome variables were survivors' quality of care and health outcome, and the predictor variable was PPR (communication, emotional support, time spent, and survivors' shared-decision making). A sample of 223 Black cancer survivors (age 63.0 ± 14.0 years) provided evaluable data. The most common cancer types reported by the participants were: gynecologic (32.7%), genitourinary (21.5%), and gastrointestinal cancers (11.2%). After controlling for covariates. A Structural Equation Model (SEM) showed that PPR was significantly associated with both health outcome (p = .015) and quality of care (p = .002). When PPR and quality of care were tested in the mediation model, the direct association between PPR and health outcome was attenuated, and it was no longer significant (b = -0.05, SE = 0.11, p = .65). However, indirectly, there was a strong association between PPR and health outcome through the quality of care (b = 0.22, SE = 0.08, p = .003), indicating full mediation. Providers' interpersonal relationships had a significant influence on the health of Black survivors, and this influence may be due to the increased positive perception of the quality of care. The implications of these findings for further research are discussed.

Racial/Ethnic Differences in Comprehension of Biospecimen Collection: a Nationwide University of Rochester Cancer Center NCI Community Oncology Research Program Study.

To examine whether (a) non-minority participants differed from racial minority participants in the understanding of biospecimens collected for research purposes, (b) patients differed from comparison group in their understanding of the ways their biospecimens could be used by researchers, and (c) participants received adequate information before consenting to donate blood for research studies. We analyzed cross-sectional data from female breast cancer patients scheduled to receive chemotherapy at the National Cancer Institute (NCI) Community Oncology Research Program (NCORP) clinical sites and a healthy comparison group. After reading a consent form related to biospecimens and consenting to participate in a clinical trial, participants' understanding of biospecimen collection was evaluated. Linear models were used to compare scores between non-minority and racial minority participants as well as cancer and non-cancer comparisons adjusting for possible confounding factors. A total of 650 participants provided evaluable data; 592 were non-minority (Caucasian) and 58 participants were a racial minority (71% Black and 29% other). There were 427 cancer patients and 223 comparisons. Non-minority participants scored higher than racial minorities on relevance-to-care items (diff. = 0.48, CI 0.13-0.80, p = 0.001). Comparison group scored higher than cancer patients on relevance-to-care items (diff. = 0.58, CI 0.37-0.78). A moderate number of the participants exhibited a poor understanding of biospecimen collection across all racial/ethnic backgrounds, but racial minority participants' scores remained lower in the relevance-to-care subscale even after adjusting for education and reading level. Differences were also noted among the patients and comparison group. Researchers should facilitate comprehension of biospecimen collection for all study participants, especially racial minority participants.

Nutritional Interventions for Treating Cancer-Related Fatigue: A Qualitative Review.

Cancer-related fatigue (CRF) is a debilitating syndrome that persists for many cancer survivors for years after treatment. Symptoms include early and persistent fatigue, functional decline, depression, and cognitive difficulties. Inflammation, assessed using pro-inflammatory biomarkers, is increased in cancer survivors with fatigue and treatments for fatigue are often aimed at reducing inflammation. Additionally, cancer and its treatment lead to nutritional complications, changes in body composition, and nutritional deficiencies that potentially weaken the cancer survivor and impact CRF. We conducted a qualitative review of clinical trials that assessed nutritional interventions for preventing and treating CRF. Further studies were examined that used nutritional interventions to address inflammation and fatigue, due to the dearth of nutrition research directly related to CRF. Dietary intake prior to, during, and after cancer treatment appears to affect fatigue levels. Increased protein intake may help preserve lean mass and body composition. Dietary patterns that reduce inflammation, such as the Mediterranean diet and other plant-based diets, appear tolerable to cancer survivors and may reduce fatigue. Supplementation with ginseng, ginger, or probiotics may improve cancer survivors' energy levels. Nutritional interventions, alone or in combination with other interventions should be considered as therapy for fatigue in cancer survivors.

Preliminary evaluation of novel Bodily Attention Task to assess the role of the brain in chemotherapy-induced peripheral neurotoxicity (CIPN).

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a common, sometimes dose-limiting side effect of neurotoxic chemotherapy. Treatment is limited because its pathophysiology is poorly understood. Compared to research on peripheral mechanisms, the role of the brain in CIPN is understudied and it may be important to develop better treatments. We propose a novel task that assesses brain activation associated with attention to bodily sensations (interoception), without the use of painful stimulation, to understand how CIPN symptoms may be processed in the brain. The goals of this preliminary study were to assess, 1) feasibility of the task, 2) sensitivity to changes in brain activity, and 3) suitability for assessing relationships between brain activation and CIPN severity. Eleven participants with varying types of cancer completed a brain fMRI scan and rated CIPN severity (CIPN-20) before and/or 12 weeks after starting neurotoxic chemotherapy. The Bodily Attention Task is a 7.5-min long fMRI task involving attentional focus on the left fingertips, the heart, or a flashing word "target" for visual attention (reference condition). Feasibility was confirmed, as 73% of all data collected were usable and participants reported feeling or focus during 75% of the trials. Regarding brain activity, finger attention increased activation in somatosensory regions (primary sensory cortex, insula) and sensory integration regions (precuneus, dorsolateral prefrontal cortex). Exploratory analyses suggested that brain activation may be associated with CIPN severity. A larger sample size and accounting of confounding factors is needed to test for replication and to identify brain and interoceptive biomarkers to help improve the prediction, prevention, and treatment of CIPN.

Mediterranean-style dietary interventions in adults with cancer: a systematic review of the methodological approaches, feasibility, and preliminary efficacy.

BACKGROUND: Cancer and its treatments can lead to excess body fat, decreases in lean mass, cardiotoxicity, and other side effects. The Mediterranean diet (MED-diet) has the potential to improve clinical and supportive care outcomes. The aim of this systematic review was to evaluate the feasibility, safety, and efficacy of the MED-diet on health outcomes in adults with cancer. METHODS: Three databases were searched from inception to February 2023. Eligible studies included randomised controlled trials testing a MED-diet intervention among adults with cancer. Within- and between-group differences for adherence, dietary intake and health outcomes were extracted. RESULTS: Fifteen studies describing fourteen interventions were included, and there were considerable differences in study design and implementation of the MED-diet. Studies were predominately in women with a history of breast cancer. The MED-diet was safe with no adverse events reported, and feasible with high adherence and/or increases in MED-diet-compliant foods. The MED-diet when applied with an energy restriction below estimated requirements for weight loss demonstrated reductions in body weight (range: -3.9 kg to -0.7 kg). Interventions that showed significant reductions in body weight also improved quality of life. There is limited evidence to evaluating the MED-diet on cardiovascular and inflammatory markers, and heterogenous MED-diet prescriptions impede definitive conclusions on these health outcomes. CONCLUSION: The MED-diet was feasible and safe for adults with cancer. There were reported benefits for weight loss following a MED-diet when an energy restriction was applied, however further evaluation to determine the effects on cardiometabolic biomarkers and other outcomes are required.

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.