Multidimensional Fatigue Symptom Inventory Research Articles

Abstract PO4-12-09: National Physical Activity Guidelines and It’s Association with Fatigue in Patients with Breast Cancer Pre- and Post-Chemotherapy in a Prospective, Nationwide Study

Abstract Background: Cancer-related fatigue (CRF) is one of the most pervasive side effects of cancer and its treatment, reported by nearly 90% of patients. Physical activity (PA) during treatment may prevent or lessen CRF burden. Current aerobic PA guidelines for cancer patients recommend at least 150 minutes of moderate PA or 75 minutes of vigorous PA or some equivalent combination of moderate and vigorous PA (MVPA). Many patients have difficulty meeting these guidelines during treatment, however, meeting these guidelines may not be necessary to alleviate CRF. This study evaluated patterns of PA below the recommended guidelines and their association with CRF in cancer patients during treatment. Methods: In a nationwide, prospective cohort study of patients with stage I-IIIC breast cancer (n=580) we assessed the relationship between self-reported PA (Aerobics Center Longitudinal Study PA) and CRF (Multidimensional Fatigue Symptom Inventory, MFSI) pre- and post-chemotherapy. Spearman correlations were utilized to evaluate the association of all PA (MET hr/wk) and MVPA (MET hr/wk) with overall CRF (total MFSI) and 5 CRF subdimensions (general, physical, emotional, mental CRF and vigor) at pre- and post-chemotherapy. ANCOVA estimated mean CRF score according to whether patients weekly MVPA (1) met 100% of the PA guidelines, (2) met 50%-99% of the PA guidelines (75-149 minutes), or (3) did not meet 50% of the PA guidelines (< 75 minutes). Results: Pre-chemotherapy, only 34% of participants met the PA guidelines, post-chemotherapy, only 21% of patients met the PA guidelines. At both time points, we observed small to moderate inverse correlations of MVPA with overall CRF and several subdimensions of CRF (Table 1; r = -0.11, -0.19). Pre-chemotherapy, those who did not meet 50% of the PA guidelines report significantly higher total CRF compared to those who met the PA guidelines (12.5 ± 1.2 vs 5.3 ± 1.5; p< 0.001). However, those who met only 50%-99% of the PA guidelines, had comparable total CRF to those who fully met the PA guidelines (7.2 ± 2.2; p=0.474). A similar pattern was observed for the subdimensions general, mental, and physical CRF. Those who met 50% of the guidelines also had significantly lower vigor compared to those who met the guidelines (11.9 ± 0.3 vs 13.8 ± 0.4; p< 0.001), while those who met 50%-99% of the guidelines had comparable vigor to those who fully met guidelines (13.1 ± 0.6; p=0.278). Post-chemotherapy CRF was higher among all patient’s, again there was no significant difference in total, general, physical CRF and vigor between those who met the PA guidelines and those who met 50%-99% of the PA guidelines. Conclusions: All PA was consistently inversely associated with CRF pre- and post-chemotherapy for patients with breast cancer. Current minimum aerobic PA guidelines for patients with cancer are difficult to achieve during treatment. Lower doses of MVPA than the current PA guidelines suggest may provide equal benefit and represent a more achievable goal for patients with cancer. Table 1: Spearman correlations of CRF and physical activity in patients with breast cancer pre- and post-chemotherapy. Table 2: ANCOVA; Mean CRF score according to the PA guidelines. Citation Format: Lindsey Mattick, Hongying Sun, Karen Mustian, Luke Peppone, AnnaLynn Williams, Po-Ju Lin, Evelyn Arana, Jeremy McGuire, Amarinthia Curtis, Alison Conlin, Lora Weiselberg, Michelle Janelsins. National Physical Activity Guidelines and It’s Association with Fatigue in Patients with Breast Cancer Pre- and Post-Chemotherapy in a Prospective, Nationwide Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-12-09.

Type I interferons, inflammation, and fatigue in a longitudinal RNA study of women with breast cancer

BackgroundFatigue is a common side effect of cancer and its treatment and is thought to be driven in part by activation of the proinflammatory cytokine network. However, the cellular and molecular underpinnings of cancer-related fatigue (CRF) have not been determined, nor have immune pathways beyond inflammation been carefully investigated. The goal of this study was to examine the association between CRF and activation of canonical proinflammatory gene regulation pathways and Type I interferon (IFN) signaling pathways in breast cancer patients during and after treatment. MethodsWomen diagnosed with early-stage breast cancer (n = 181) completed assessments before and after treatment with radiation and/or chemotherapy and at 6, 12, and 18-month post-treatment follow-ups. Assessments included self-reported fatigue (Multidimensional Fatigue Symptom Inventory – Short Form) and expression of pre-specified sets of Type I IFN and pro-inflammatory immune response genes determined from mRNA sequencing of PBMCs. Mixed effect linear models examined changes in fatigue and immune gene expression over time and tested the hypothesis that fatigue would be associated with increased expression of Type I IFN and inflammatory response genes. ResultsThere were significant changes in fatigue and immune gene expression across the assessment period; all measures increased from pre- to post-treatment but showed diverging patterns over the follow-up, with declines in fatigue and persistent elevations in Type I IFN and proinflammatory gene expression. In mixed effect linear models, expression of Type I IFN response genes was elevated in association with fatigue across the assessment period, from pre-treatment to 18-month follow-up. In contrast, pro-inflammatory gene expression was associated with fatigue only at 6, 12, and 18-month follow-ups. Analyses controlling for changes in leukocyte subsets continued to show a significant association between fatigue and Type I IFN gene expression but reduced the time-dependent association with pro-inflammatory gene expression to non-significant. ConclusionsResults revealed unexpected complexity in the immune underpinnings of CRF and identify a novel role for IFN signaling as a robust contributor to this symptom before, during, and after treatment. Pro-inflammatory gene expression emerged as a predictor of fatigue later in the cancer trajectory, and that effect was primarily accounted for by a concurrent increase in monocyte prevalence.

17 Comparing Cognitive Patient-Reported Outcomes with Neuropsychological Impairment in Patients with Diffuse Glioma.

Objective:Cognitive difficulties among diffuse glioma survivors are common in survivorship due to cancer treatment effects (i.e., surgery, chemotherapy, and/or radiation therapy), which can diminish quality of life. Routine monitoring of cognitive symptoms in survivorship is recommended and can help address patient needs and inform clinical interventions (e.g., cognitive rehabilitation). While several patient-reported outcome (PRO) measures have been used in brain tumor populations, there has been few studies comparing the performance of these PROs in patients with diffuse glioma. In order to better understand the value of different PROs, we conducted preliminary analyses associating cognitive PROs with neuropsychological impairment in a well-characterized sample of patients with diffuse glioma.Participants and Methods:23 glioma patients (mean aged 44.26 ± 12.24), six or more months after completing cancer treatment, underwent comprehensive psychosocial and neuropsychological assessments. The neuropsychological battery included the Hopkins Verbal Learning Test - Revised, Brief Visuospatial Memory Test - Revised, Wechsler Adult Intelligence Scale-IV tests of Coding and Digit Span, Trail-Making Test, Stroop Test, FAS, Animals, Boston Naming Test, and Rey-Osterrieth Complex Figure (copy). Completed cognitive PROs included the Functional Assessment of Cancer - Cognitive Function and Brain questionnaires (FACT-Cog; FACT-Br), the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire for Brain Neoplasms (EORTC QLQ-BN20), and the Multidimensional Fatigue Symptom Inventory, short form (MFSI-SF) Mental subscale. Based on published norms, we divided the sample into cognitively impaired and non-impaired groups (two or more primary neuropsychological test scores <= -2 z-score). We compared PRO scores between impaired and non-impaired groups using Mann-Whitney U tests. Higher medians equate to better cognitive functioning for all PROs, except for the MSFI-SF.Results:We found significantly worse scores in the impaired group compared to non-impaired group on the FACT-Cog subscales of perceived cognitive ability (PCA), [Non-Impaired (Mdn = 21, n = 11), Impaired (Mdn = 10, n = 12), U = 22.5, z = -2.68, = 0.007], perceived cognitive impairment (PCI), [Non-Impaired (Mdn = 59, n = 11), Impaired (Mdn = 44, n = 12), U = 32.5, z = -2.06, p=0.039]. The impaired group also trended towards worse scores on the FACT-Br additional concerns subscale [Non-Impaired (Mdn = 79.5, n = 10), Impaired (Mdn = 61, n = 12), U = 32.5, z = -1.81, p=0.07]. Group differences were not observed on the MSFI-SF [Non-Impaired (Mdn = 5, n = 11), Impaired (Mdn = 7, n = 12), U = 40.5, z = -1.57, p=0.12], or EORTC Cognitive Functioning subscale [Non-Impaired (Mdn = 83.33, n = 10), Impaired (Mdn = 75, n = 12), U = 42, z = -1.23, p=0.218].Conclusions:The preliminary findings suggest that the FACT-Cog, especially the PCA and PCI correspond with neuropsychological impairment among diffuse glioma survivors better than other cognitive PROs. The FACT-Br subscale was somewhat effective. The MFSI-SF Mental and EORTC Cognitive Functioning subscales did not correspond to impairment status. The FACT-Cog is a promising instrument and future work is needed to better determine relative utility of cognitive PROs in this population.

Effects Of Yoga Vs. A Behavioral Placebo On Cancer-related Fatigue Among Cancer Survivors

Cancer-related fatigue (CRF) is a multidimensional treatment-related toxicity that is commonly experienced by patients with cancer. We have previously shown that yoga (i.e., Yoga for Cancer Survivors, YOCAS©®), compared to usual care, significantly reduced CRF in cancer survivors at post-intervention. Whether yoga is more effective than a rigorous behavioral placebo (i.e., Survivorship Health Education, SHE) for treating CRF and whether those improvements are sustained 3 and 6 months after the completion of the intervention are unknown. PURPOSE: We conducted a nationwide, multicenter, blinded, phase III RCT comparing the effects of yoga with a behavioral placebo on CRF at post-intervention, and 3 and 6 months later in cancer survivors. METHODS: Cancer survivors 2-60 months post-treatment with insomnia, no distant metastatic disease, and no yoga participation within 3 months prior were randomized to receive eight 75-minute YOCAS©® or SHE sessions (2x/wk. for 4 wks.). CRF was assessed by the Multidimensional Fatigue Symptom Inventory, which generates an overall CRF score and 5 CRF subdomain scores (i.e., general, physical, emotional, and mental fatigue and vigor), at baseline, post-intervention, and 3 and 6 months after completing the interventions. Mixed linear models were used to assess intervention effects on CRF. RESULTS: 502 eligible cancer survivors (94% women, mean age 56 yrs., 74% breast cancer) were randomized to YOCAS©® (n = 251) or SHE placebo (n = 251). YOCAS©® participants demonstrated significantly greater improvements in overall CRF (-3.7 ± 1.4), general (-1.8 ± 0.5), and mental (-0.7 ± 0.4) CRF subdomains, compared to SHE placebo participants, at post-intervention (all p ≤ 0.05). YOCAS©® participants also showed greater improvements, compared to SHE placebo participants, in overall (-2.4 ± 1.5, p ≤ 0.10), general (-1.1 ± 0.5, p ≤ 0.05), and mental (-0.6 ± 0.4, p ≤ 0.10) CRF 3 months later, with no group differences in overall CRF or subdomains of CRF at the 6-month follow-up. CONCLUSIONS: YOCAS©® is effective for treating overall CRF, as well as, general and mental subdomains of CRF, among cancer survivors immediately post-intervention with improvements in CRF sustained 3 months later. YOCAS©® should be recommended for treating CRF in survivors. Funding: NCI UG1CA189961, R01CA181064, T32CA102618

Aromatherapy blend of thyme, orange, clove bud, and frankincense boosts energy levels in post-COVID-19 female patients: A randomized, double-blinded, placebo controlled clinical trial

BackgroundA large proportion of individuals who have recovered from an acute COVID-19 infection continue to experience symptoms months later. Post-acute COVID-19 (long-haul COVID-19) can range from serious complications to quality of life symptoms such as fatigue or insomnia. The purpose of this study was to evaluate the potential for inhalation of essential oils to improve energy levels among otherwise healthy female survivors of acute COVID-19 who experience a lack of energy more than five months after recovery. This study was conducted in the United States in late 2021. MethodThis was a randomized double blind, placebo controlled trial to evaluate the potential for inhalation of Longevity™, a proprietary essential oil blend manufactured by Young Living Essential Oils (Lehi, Utah, USA), on energy levels among female survivors of COVID-19 who continue to experience fatigue more than 5 months recovery from the acute infection. Forty women were randomized to two groups: intervention and placebo. Both groups inhaled the assigned product twice daily for fourteen consecutive days. Fatigue scores were measured using the Multidimensional Fatigue Symptom Inventory (MFSI). Secondary outcomes included scores on each of the MFSI’s ten subscales. ResultsIndividuals who inhaled the essential oil blend for 2 weeks had significantly lower fatigue scores after controlling for baseline scores, employment status, BMI, olfactory function, and time since diagnosis, with a large effect size (F (1,39) = 6.15, p = .020, partial eta squared = 0.198). Subscale analysis identified subscales of vigor, as well as global, behavioral, general, and mental fatigue as benefiting from the intervention. This study provides evidence that a proprietary aromatherapy blend can significantly improve energy levels among women who are experiencing fatigue after recovering from COVID-19.

Multisensory mental imagery of fatigue: Evidence from an fMRI study.

Functional imaging experimental designs measuring fatigue, defined as a subjective lack of physical and/or mental energy characterizing a wide range of neurologic conditions, are still under development. Nineteen right‐handed healthy subjects (9 M and 10 F, mean age 43.15 ± 8.34 years) were evaluated by means of functional magnetic resonance imaging (fMRI), asking them to perform explicit, first‐person, mental imagery of fatigue‐related multisensory sensations. Short sentences designed to assess the principal manifestations of fatigue from the Multidimensional Fatigue Symptom Inventory were presented. Participants were asked to imagine the corresponding sensations (Sensory Imagery, SI). As a control, they had to imagine the visual scenes (Visual Imagery, VI) described in short phrases. The SI task (vs. VI task) differentially activated three areas: (i) the precuneus, which is involved in first‐person perspective taking; (ii) the left superior temporal sulcus, which is a multisensory integration area; and (iii) the left inferior frontal gyrus, known to be involved in mental imagery network. The SI fMRI task can be used to measure processing involved in mental imagery of fatigue‐related multisensory sensations.

Abstract P3-19-29: Polygenic risk scores predict toxicities in racially diverse breast cancer patients following radiotherapy

Abstract Purpose: Fatigue, fibrosis, and breast asymmetry are the most common side effects of radiotherapy, experienced in up to 40% of survivors long term. Due to the prevalence of these toxicities, a number of patient, tumor, and treatment-related characteristics have been studied in an attempt to identify at risk individuals. Additionally, several single nucleotide polymorphisms (SNPs) such as those that reside in gene TGFB1 have been associated with long-term breast fibrosis following radiotherapy by genome-wide association studies (GWAS). However, these findings are often not consistently replicated in various cohorts, particularly those with racially diverse patients, indicating that these significant SNPs (with p < 5e-8) or clinical factors alone may not provide enough information to determine individual risk for radiation-related toxicities. We hypothesized that the Polygenic Risk Scores (PRS) derived from the GWAS summary statistics of a larger number of potentially significant SNPs (e.g. with p-values < 0.05) have the potential to improve risk prediction, especially by using GWAS data of a racially diverse cohort. Methods: We conducted three prospective, longitudinal studies of breast cancer patients treated with whole breast radiotherapy with or without regional nodal irradiation. In all studies, fatigue, skin thickening, and breast asymmetry were assessed before and 12-18 months post radiotherapy using the following identical measures: percentage breast retraction assessment (pBRA) calculated from digital photographs, skin thickening objectively measured on ultrasound images (STRA), and fatigue assessed by the Multidimensional Fatigue Symptom Inventory (MFI) 20-item scale. We profiled genome-wide SNP data from peripheral blood samples of enrolled patients (n=176; 44% African Ancestry; 56% European Ancestry) by Affymetrix arrays and then imputed these genotyped SNPs to 1000 Genome Phase III reference panel. Genotyped or imputed SNPs with imputation R2>0.3 with minor allele frequency (MAF) > 5% (~10M) were analyzed in our GWAS with baseline, post radiotherapy, and changes in pBRA, STRA, and MFI. GWAS was first conducted separately in African and European ancestry samples, and then combined by meta-analysis for baseline and post radiotherapy measurements. Joint GWAS was conducted on all samples for the change phenotypes as we observed no heterogeneous phenotype distribution for samples of different ancestries. PRS was derived using the GWAS summary statistics for each phenotype. Results: Twelve independent significant SNPs were identified for baseline and post radiotherapy measurements in pBRA, STRA, and MFI, all of which were identified only in patients of African and not European ancestry due to low MAF < 5%. All post radiotherapy PRS were significantly correlated with the corresponding baseline (r>0.29, p < 0.05) and change PRS (r>0.19, p <0.05). Importantly, PRS accounted for 76%, 73%, and 79% of the variance of changes in pBRA, STRA, and MFI after radiation. When clinical (e.g. breast volume and age) and treatment-related factors (e.g. radiation dose, chemotherapy treatment) were added as additional covariates to the respective PRS, the prediction R2 increased to 92%, 96%, and 96% for changes in pBRA, STRA, and MFI, respectively. Conclusions: Our findings indicate that over 70% of the variation in fatigue, skin thickening and breast asymmetry changes experienced by breast cancer patients after radiotherapy may be explained by PRS, which can be derived from our GWAS summary statistics and SNP data profiled from blood samples prior to radiotherapy. Genome-wide significant risk SNPs of baseline and post radiotherapy measurements of pBRA, STRA, and MFI were found only in samples of patients of African ancestry. Future studies aimed at replicating our findings in larger cohorts are needed. Citation Format: Mylin Ann Torres, Tian Liu, Boran Zhou, Xiaofeng Yang, Gabrielle Brown, India Green, Jolinta Lin, Andrew H Miller, Jingjing Yang. Polygenic risk scores predict toxicities in racially diverse breast cancer patients following radiotherapy [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-29.

Acute and chronic fatigue in nurses providing direct patient care and in non-direct care roles: A cross-sectional analysis.

Nurses are at risk for work-related fatigue, which can impact their health, well-being, and job readiness. The purpose of this study was to examine the levels, types, and factors associated with fatigue in registered nurses (RNs) in direct patient care (DCRNs) and in non-direct patient care (non-DCRNs) roles. A cross-sectional survey was administered to 313 RNs. Measures included: Multidimensional Fatigue Symptom Inventory, Occupational Fatigue Exhaustion Recovery, Brief COPE, PROMIS® Global Sleep Disturbance, and Job Content Questionnaire. Acute fatigue levels in RNs were similar to those in diseased populations, and nearly 50% reported moderate/high levels of chronic fatigue. DCRNs reported higher levels of acute and chronic fatigue than non-DCRNs, but the differences were small and disappeared when accounting for other factors associated with fatigue including sleep disturbance, job strain, workplace support, maladaptive coping, and especially intershift recovery, which accounted for 20%-41% of fatigue variability. This study suggests that it may not be only nurses providing direct patient care who are at risk for acute and chronic fatigue. Intershift recovery may be particularly important in alleviating acute and chronic fatigue in nurses.

Development of a patient reported outcome questionnaire to measure the impact of postpartum blood loss in women with moderate and severe anaemia: A study using a multi-faceted approach

Background: Globally, over one-third of pregnant women are anaemic and are at increased risk of postpartum haemorrhage (PPH). Tranexamic acid (TXA) given within 3 hours of birth significantly reduces death due to bleeding in women with PPH. However, for many, treatment is too late to prevent death from PPH. The WOMAN-2 trial aims to see if giving TXA can prevent PPH and other outcomes in women with moderate and severe anaemia. Assessing the impact of postpartum blood loss on women’s own perceptions of their health and well-being is an important outcome for the WOMAN-2 trial. This study aimed to develop a conceptual framework and questionnaire to measure the impact of postpartum blood loss on participant-reported outcomes (PRO) in women with moderate and severe anaemia. Methods: A conceptual framework and PRO questionnaire were developed using a multifaceted, iterative process. Factors influencing anaemic women’s postpartum experience were identified from review of the literature and through group discussion with them. De novo items were combined with those from an existing instrument (Multi-dimensional Fatigue Symptom Inventory, Short Form (MFSI-SF)). Content validity was tested among a group of obstetricians and anaemic postpartum women, revised and then pilot tested among 124 women with moderate and severe anaemia following vaginal birth. Results: Women with moderate and severe anaemia who experienced PPH reported more fatigue on the MFSI-SF (p=0.001); reported feeling more ill (p=0.004); and had greater difficulty breastfeeding (p=0.039), compared to those who did not experience PPH. Compared to women with moderate anaemia, women with severe anaemia reported experiencing worse symptoms of anaemia (p=0.001) and scored worse on the MFSI-SF (p=0.007). Conclusions: Significant differences between the scores of women who developed PPH and those who did not and the scores between women with moderate and severe anaemia indicate that the questionnaire had satisfactory construct validity.

Assessment of fatigue among aviation personnel involved in military flying in India employing Multidimensional Fatigue Symptom Inventory – Short Form (MFSI-SF)

Introduction: Fatigue has been recognized as a major safety hazard in modern aviation. There are numerous studies which have addressed various aspects such as the subjective symptoms, objective measures to diagnose fatigue, and its link with operator’s performance. This study was a novice attempt to assess the chronic fatigue among the aviation personnel employing “Multidimensional Fatigue Symptom Inventory – Short Form (MFSI-SF),” which is a well validated fatigue questionnaire. Material and Methods: A total of 93 aircrew and 30 ground crew of either sex from three military air bases were randomly selected for this cross-sectional observational study. The selected participants were requested to respond to 30 items listed in the survey form based on various types of symptoms along with severity that they experienced in the preceding 1 week. Results: The total fatigue score in case of the studied ground crew was higher than the studied aircrew group and this was statistically significant (P = 0.00001). The fighter, transport, and helicopter groups were not different from each other as far as their total fatigue score is concerned. However, ground crew group had significantly higher score in comparison to the score of the fighter, transport, and helicopter groups. In this study, 43.33% of ground crew participants and 11.82% of aircrew participants were observed to have fatigue. On stream-wise analysis, 2.94% of transport aircrew, 14.28% of fighter aircrew, 20.83% of helicopter aircrew, 52.17% Air Traffic Control (ATC) ground crew, and 14.28% of other ground crew who had participated in this study were fatigued. Conclusion: Fatigue in either form, i.e., acute or chronic, could affect both aircrew and ground crew. The present study had revealed that the proportion of ground crew suffering from chronic fatigue was more than the aircrew. The aircrew who were found to have such type of fatigue were younger in age and experience in comparison to their counterpart ground crew. Among the ground crew, a large percentage of ATC crew had this form of fatigue.

Association of mitochondrial DNA content and displacement loop region sequence variations with cancer-related fatigue in breast cancer survivors receiving chemotherapy

Cancer-related fatigue (CRF) is characterized by a lack of energy, and mitochondrial dysfunction is postulated to contribute to its etiology. This prospective cohort study assesses the self-reported fatigue levels of early-stage breast cancer patients using the validated Multi-Dimensional Fatigue Symptom Inventory–Short Form (MFSI-SF) and blood samples drawn at three time points: before treatment, approximately 6 weeks, and 12 weeks after the initiation of chemotherapy. The aim of this study is to evaluate mitochondrial measures with CRF, over the course of chemotherapy using mitochondrial DNA (mtDNA content) and displacement loop (D-loop) region sequence variations at nucleotide positions 303, 489 and 514. The relative mtDNA copy number was determined via real-time quantitative polymerase chain reaction and compared between study time points and D-loop sequence variants. The association of mtDNA content with MFSI-SF total and sub-domain scores was analyzed in a sample of 155 patients (mean age ± SD: 51.7 ± 8.8 years). The median mtDNA content decreased over 12 weeks after the initiation of chemotherapy (p < 0.001). Baseline mtDNA content was lower for nucleotide position 303 in sequence variations than for the reference sequence (67.2 copies vs 79.1 copies, p = 0.03). Physical fatigue negatively correlated with mtDNA content in both unadjusted (β = −0.0075, p = 0.048) and adjusted models (β = −0.0062, p = 0.042), accounting for age, anxiety, insomnia, haemoglobin levels and body mass index. Our findings add to the literature indicating that mitochondrial function serves as an important target for mitigating CRF.

Novel Biomarkers Of Treatment-Induced Muscle Damage, Exercise And Fatigue: An RCT In Breast Cancer Patients

Radiation and hormone therapy may damage skeletal muscle and lead to cancer-related fatigue (CRF). Developmental myosin light chain 5 (MYL5) and myosin heavy chain 8 (MYH8) are required for normal muscle regeneration. Up-regulated serum levels of MYL5 and MYH8 resulting from radiation and hormone therapy may increase muscle degradation and lead to CRF, especially physical CRF—one of the multidimensional subcomponents of overall CRF. PURPOSE: To investigate the effect of a 6-week aerobic and anaerobic exercise intervention, called Exercise for Cancer Patients (EXCAP), on (1) CRF (overall and physical), (2) serum protein levels of MYL5 and MYH8, and (3) the association of CRF (overall and physical) with these novel biomarkers. METHODS: Ninety sedentary breast cancer patients (55.5±9.6 years, 79% white, 52% receiving radiation therapy, 48% receiving hormone therapy) were consented and participated in this phase II RCT. Patients were randomized into two arms: (1) standard cancer treatment (Control) or (2) standard cancer treatment plus EXCAP. Serum levels of MYL5 and MYH8 by ELISA assays and CRF (total and physical) by patient-report via the Multidimensional Fatigue Symptom Inventory were assessed pre- and post-intervention. RESULTS: T-tests showed significant reductions in overall CRF and physical CRF among exercisers (overall CRF: -4.9±2.6, p=0.07, physical CRF: -1.0±0.5, p=0.05) but not in controls, with significant group differences (overall CRF: -7.9±3.4, p=0.02; physical CRF: -1.9±0.7, p<0.01). T-tests also revealed statistical trends for down-regulation of MYL5 (-0.5±0.3, p=0.17) and MYH8 (-0.4±0.3, p=0.17) serum protein levels from pre- to post-intervention in exercisers, but not in controls. Spearman correlations also reveal statistical trends, in exercisers, where decreases in MYL5 and MYH8 serum protein levels are directly associated with decreases in total CRF (MYL5 r=0.23, p=0.17; MYH8 r=0.30, p=0.07) and physical CRF (MYL5 r=0.29, p=0.08; MYH8 r=0.39, p=0.02). CONCLUSIONS: EXCAP improves overall and physical CRF. EXCAP may also protect against cancer treatment-induced skeletal muscle damage via its effects on MYL5 and MYH8. Changes in these novel biomarkers may mediate changes in overall and physical CRF. Further phase III RCTs are needed to confirm these findings.

438P - Evaluating mitochondrial biomarkers between fatigue subclasses identified using latent class analysis in early-stage breast cancer patients

BackgroundGiven that CRF is characterized by a lack of energy, it is postulated that mitochondrial dysfunction may contribute to its etiology. Using mitochondrial DNA (mtDNA) copy number and displacement-loop (D-loop) mutation status, this study aims to evaluate mtDNA content between fatigue subclasses, over the course of chemotherapy. MethodsIn a prospective cohort study, early-stage breast patients’ fatigue levels were assessed using the validated Multi-Dimensional Fatigue Symptom Inventory–Short Form (MFSI-SF) and their blood was drawn before, during and after treatment. Relative mtDNA copy number was determined via real-time quantitative polymerase chain reaction while mitochondrial genome was sequenced directly for D-loop mutations at nucleotide positions 303, 489 and 514. Subclasses of extent of fatigue was derived using latent class analysis, based on magnitude of change in sub-domain scores after treatment, with respect to baseline. Clinically relevant factors that differentiate the identified subclasses were then compared between the fatigued groups. ResultsA total of 133 patients (mean age ± SD: 51.2±8.8 years, median mtDNA: 71.0) were classified into two fatigue subclasses: mild fatigue (75.2%) and fatigued group (24.8%) respectively. Based on mtDNA trajectory, patients who are predisposed to CRF started off with lower baseline values and experienced slower recovery. Median mtDNA content was reduced over 12 weeks after initiation of chemotherapy (p < 0.001) and was reported to be consistently lower in fatigued group (T2: 48.0 vs 56.0; T3: 61.4 vs 66.0) although the difference was not found to be statistically significant. The proportion of patients with D-loop mutation status was comparable between fatigued group and mild fatigue (303: 81.8% vs 73.0%, 489: 45.5% vs 47.0% and 514: 45.5% vs 53.0%). However, no association was reported between mtDNA levels over time or D-loop mutation with CRF status. ConclusionsmtDNA content and D-loop mutation status do not sufficiently differentiate fatigue subclasses, suggesting that future research may be needed to study the differential expression of mitochondrial dysfunction-related genes and the pathways they may perturb. Legal entity responsible for the studyNational University of Singapore. FundingNational Medical Research Council. DisclosureAll authors have declared no conflicts of interest.

Aromatherapy reduces fatigue among women with hypothyroidism: A randomized placebo-controlled clinical trial.

Background This randomized, blinded, placebo-controlled clinical trial identifies the effect of an aromatherapy blend of essential oils on fatigue, which is one of the most commonly unaddressed symptoms of hypothyroidism, by evaluating the effects of daily aromatherapy inhalation. Methods Participants included women aged 18-55 with a diagnosis of hypothyroidism. Women who had a history of thyroid cancer were excluded, due to the confounding effects of cancer on fatigue as the outcome of interest. Participants were randomized into two groups: the aromatherapy group, treated with inhalation of the essential oil blend, and the control group, treated with an odorless vegetable oil blend. The primary outcome was change from baseline in fatigue scores as measured by the Multidimensional Fatigue Symptom Inventory (MFSI), a validated instrument which measures multiple patterns of fatigue. Results After adjusting for baseline scores, no significant difference was found between the aromatherapy group and the control group at midpoint. Both groups experienced a reduction in symptoms during the first week of the intervention. At the endpoint, participants in the aromatherapy group had improved fatigue scores across all ten subscales, as compared to the control group. Not all improvements achieved statistical significance, indicating that the aromatherapy treatment has a greater effect on the subscales of global, affective, and general fatigue. Conclusions This is the first study to evaluate the effects of aromatherapy on fatigue among women with hypothyroidism. These findings provide evidence that regular inhalation of an aromatherapy blend may reduce fatigue among women with hypothyroidism, particularly in the areas of global, affective, and general fatigue.

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

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. 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 6months post-chemotherapy. Height and weight at baseline were used to categorize subjects based on body mass index (BMI): obese (≥ 30.0kg/m2; n = 294), overweight (25.0-29.9kg/m2; n = 146), and normal weight (18.5-24.9kg/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. 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 6months post-chemotherapy, the obese patients still had significantly higher SI fatigue scores (obese = 3.5 vs normal weight = 3.0; p = 0.05). Obese patients suffered greater CRF from pre-chemotherapy through 6months post-chemotherapy. Recommendations for weight loss or weight maintenance may impact CRF levels in obese breast cancer patients before and after chemotherapy.

SLEEP DISTURBANCES AND FATIGUE AMONG WOMEN IN POSTNATAL PERIOD

Background: Sleep in the postpartum period is a concern due to robust associations with wake disturbance, fatigue, and depression. Objectives: The aim of this study was to assess sleep disturbances and fatigue among women in postnatal period. Subject and Methods: Design a descriptive study design was utilized in this study. Settings the study was carried out in six health centers in Port-Said city namely (El-Manakh, Bank El-Escan, El-Arab, El-Kuwait, Port-Fouad (2), and Omar Ebn-ElKhatab). Sample a Purposive sample was followed in the present study. The study subjects consisted of 322 postpartum women recruited from postpartum outpatient clinics in the above mentioned settings. A Structured interviewed schedule sheet, the Global Sleep Assessment Questionnaire (GSAQ), and the Multidimensional Fatigue Symptom Inventory Short (MFSI_SF). Results: The study’s results indicated that (69.6%) had high sleep disturbance, and (93.8%) had high fatigue. There was statistical significant relation between sleep disturbance and women's residence (p=0.007), women's mode of delivery (p=0.015), and women with problems after delivery (p=0.019). There were statistically significant relationship between fatigue and crowding index (p=0.009), women's residence (p=0.021), complication after delivery (p=0.009), hospital's stay after delivery (p= 0.018), and receiving help for caring the baby from their sisters (p=0.042). Conclusion: It was concluded that, the great majority of the studied women had postnatal fatigue, and about more than two-thirds of them had sleep disturbance. Factors that were increased these problems including living with extended family and high crowding index. Receiving postnatal instructions seems to decrease both sleep and fatigue problems; both sleep and fatigue were decreased with staying one day only at the hospital. While help giving at home from women's sisters was decreasing women’s sleep disturbances and fatigue compared with help from husband. There was a highly statistically significant positive correlation between sleep disturbance and fatigue. Recommendations: It was recommended that awareness program for women and nurses about caring for postnatal period and who are at risk of developing postnatal fatigue and sleep disturbances, and help them to cope with the difficulties encountered

Development of a patient reported outcome questionnaire to measure the impact of postpartum blood loss in women with moderate and severe anaemia: A study using a multi-faceted approach

Background: Globally, over one-third of pregnant women are anaemic and are at increased risk of postpartum haemorrhage (PPH). Tranexamic acid (TXA) given within 3 hours of birth significantly reduces death due to bleeding in women with PPH. However, for many, treatment is too late to prevent death from PPH. The WOMAN-2 trial aims to see if giving TXA can prevent PPH and other outcomes in women with moderate and severe anaemia. Assessing the impact of postpartum blood loss on women’s own perceptions of their health and well-being is an important outcome for the WOMAN-2 trial. This study aimed to develop a conceptual framework and questionnaire to measure the impact of postpartum blood loss on participant-reported outcomes (PRO) in women with moderate and severe anaemia. Methods: A conceptual framework and PRO questionnaire were developed using a multifaceted, iterative process. Factors influencing anaemic women’s postpartum experience were identified from review of the literature and through group discussion with them. De novo items were combined with those from an existing instrument (Multi-dimensional Fatigue Symptom Inventory, Short Form (MFSI-SF)). Content validity was tested among a group of obstetricians and anaemic postpartum women, revised and then pilot tested among 124 women with moderate and severe anaemia following vaginal birth. Results: Women with moderate and severe anaemia who experienced PPH reported more fatigue on the MFSI-SF (p=0.001); reported feeling more ill (p=0.004); and had greater difficulty breastfeeding (p=0.039), compared to those who did not experience PPH. Compared to women with moderate anaemia, women with severe anaemia reported experiencing worse symptoms of anaemia (p=0.001) and scored worse on the MFSI-SF (p=0.007). Conclusions: Significant differences between the scores of women who developed PPH and those who did not and the scores between women with moderate and severe anaemia indicate that the questionnaire had satisfactory construct validity.

Abstract P1-11-12: Effect of wearable wellness brain sensing mindfulness-based technology in newly diagnosed surgical breast cancer patients: A randomized intervention

Abstract Introduction: There is insufficient knowledge about the feasibility and effect of mind-body intervention on QOL and stress at initial diagnosis and shortly after undergoing breast cancer surgical treatment. The pre-operative and post-operative period can be stressful, distressing and anxiety provoking for many women. Mind-body interventions such as meditation, relaxation and mindfulness can offset distress and is an option to cope with the stresses of treatment. We investigated the role of wearable mindfulness based technology in patients newly diagnosed breast cancer patients. Methods: This randomized study compared the Muse EEG mindfulness sensing headset device (n=16) to a stress reduction education control group (n=13). Primary outcomes included quality of life (QOL), stress, and fatigue via validated, standardized scales/subscales: Functional Assessment of Cancer Therapies – General (FACT-G), Multidimensional Fatigue Symptom Inventory – Short Form (MFSI-SI), and the Perceived Stress Scale (PSS). Participants from an academic cancer center were randomized to the wearable device or stress education material prior to surgery. Participants completed questionnaires at initial diagnosis and at specific time points during the breast cancer surgical journey: pre-surgery, post-surgery (2 weeks), and at 3 months. Usage was directly from Muse and via written log. Was It Worth It (WIWI) survey was conducted at 3 months. Results: Mindfulness via the headset devise was feasible and worthwhile (71.4% intervention group). The scales of QOL, fatigue, and stress improved in both groups at 3 months compared to baseline (MFSI-E, MFSI-M, MFSI-V, FACT-EWB, and PSS). Participants randomized to the mindfulness headset device had improved fatigue and QOL at 2 weeks post-operatively (MFSI-E, MFSI-V, MFSI-T, FACT-PWB, FACT-EWB) and in total MFSI at 3 months. The results were not significantly different between groups. High mindfulness headset utilizers (&amp;gt;30 sessions) compared to below average utilizers differed at the 3 month visit in fatigue and QOL (MFSI-G, MFSI-P, FACT-PWB, and FACT-Total). Conclusion: Our study demonstrated that the use of wearable mindfulness sensing headset device was feasible, simple to use, low cost, and integrated into the surgical breast cancer journey. Overall, among breast cancer patients undergoing surgery there was improvement in QOL, fatigue, and stress with mind-body interventions around surgery compared to baseline. Participants randomized to the wearable mindfulness headset device trended toward outcomes sooner (2 week follow-up) and with high utilization. Further research is needed to determine significance of these outcomes and long term impact in care of cancer survivors. Citation Format: Pruthi S, Millstine DM, Bhagra A, Nguyen M-D. Effect of wearable wellness brain sensing mindfulness-based technology in newly diagnosed surgical breast cancer patients: A randomized intervention [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-11-12.

Assessing Treatment Effects Using Quality of Life Questionnaires in Pregnant Women with Iron Deficiency Anaemia [26H

INTRODUCTION: There is considerable overlap between symptoms related to iron deficiency anaemia (IDA) and a normally advancing gestation, posing challenges to the use of quality of life (QoL) tools to measure treatment effects. Our aim was to determine how best to use two existing QoL tools; short-form 36 (SF36) – a general questionnaire covering eight domains and the multidimensional fatigue symptom inventory: short form (MFSI-SF) – a fatigue-specific questionnaire to assess treatment effect in pregnant women with IDA. METHODS: We recruited consecutive women with IDA attending the Obstetric Day Unit at Mount Sinai Hospital, Toronto, for intravenous iron infusions over six months. Consenting participants completed SF36 and MFSI-SF questionnaires at each visit and upon completion of treatment. Scores for the entire questionnaire and individual domains were summed and plotted graphically over time. RESULTS: 29 women consented and completed at least one SF36 and MFSI-SF questionnaire, while 24 completed two, 12 completed three and four women completed four. The mean maternal age was 34 (24-46) years and the mean gestational age 29 (25-38) weeks. These women represented different ethnic groups and socio-economic strata. Although there was no consistent pattern in scores for 6/8 SF36 domains, there was a significant improvement between visits in the energy/fatigue (37.6 vs 42.8, p=0.044), and emotional wellness (62.7 vs 77.3, p&lt;0.001) domains and in MFSI-SF scores (17.1 vs 12.2, p=0.025). CONCLUSION: When assessing treatment effects in pregnant women with IDA, consideration should be given to using QoL tools specifically designed to measure fatigue, such as MFSI-SF or the energy/fatigue domain in SF36.

Oncology Section EDGE Task Force on Cancer: Measures of Cancer-Related Fatigue—A Systematic Review

Background: Cancer-related fatigue (CRF) is one of the most common side effects of cancer and cancer treatment. Being able to accurately screen for and assess CRF will improve access to and prescriptions for interventions. Valid and reliable measures to screen for and assess CRF need to be identified. Purpose: To identify and recommend reliable, valid, and clinically useful tools to screen for and assess CRF among those treated for cancer. Methods: A systematic review of the literature was conducted to assess the published psychometric properties and clinical feasibility of each method identified. Task force members independently reviewed each measure using the Cancer EDGE Rating Form. Results: Review of 136 studies resulted in recommendations for 14 questionnaires. Five unidimensional and 9 multidimensional questionnaires are recommended by the Oncology EDGE Task Force. Conclusion: The 10-point Numeric Rating Scale for Fatigue is best as a screening tool, whereas the Multidimensional Fatigue Symptom Inventory is a highly recommended multidimensional tool. Ease of screening can promote referral for interventions, whereas thorough assessment drives appropriate interventions.