EORTC Fatigue Research Articles

Effect of physical exercise on cognitive function after chemotherapy in patients with breast cancer: A randomized controlled trial (PAM study).

12015 Background: Chemotherapy is associated with cognitive problems. Physical exercise is a promising intervention. We investigated whether exercise improves cognition in chemotherapy-exposed breast cancer (BC) patients 2-4 years after diagnosis. Methods: In the PAM study, we randomized chemotherapy-exposed BC patients with self-reported and test-confirmed cognitive problems to an exercise or control group. The 6-month exercise intervention consisted of 2 hours of supervised aerobic and resistance training and two hours of Nordic/power walking. Memory function measured with the Hopkins Verbal Learning Test-Revised (HVLT-R) was our primary outcome. Further measurements included online neuropsychological tests (Amsterdam Cognition Scan; ACS), self-reported cognitive complaints (MDASI-MM, EORTC QLQ C-30 cognitive functioning), physical fitness (VO2peak), fatigue (MFI, EORTC fatigue), quality of life (QoL; EORTC), anxiety (HADS) and depression (HADS, PHQ9). HVLT-R total recall was analyzed with a Fisher exact test for clinically relevant improvement of ≥5 words. Other outcomes were analyzed using multiple regression analyses adjusted for baseline and stratification factors. An hypothesis driven but not pre-specified analysis in patients with high baseline EORTC fatigue levels (≥39) was performed. Results: We randomized 181 patients to the exercise (n = 91) or control group (n = 90). Two-third of the patients attended ≥ 80% of the exercise program and physical fitness significantly improved compared to the control patients ( VO2peak1.4 ml/min/kg, 95% CI 0.6; 2.2). No difference in favor of the intervention group was seen on the primary cognitive outcome or other cognitive tests. However, significant beneficial intervention effects were found for self-reported cognition (MDASI-MM Severity (-0.7, -1.2;-0.1)), fatigue (general fatigue (-2.2, -3.3; -1.1), physical fatigue (-3.3, -4.4; -2.2), mental fatigue (-1.0, -2.0; 0.0), reduced motivation (-1.1, -2.0; -0.2) and reduced activity (-2.1, -3.2; -1.1)), QoL (summary score (4.0, 1.2; 6.7), global health status (5.8, 1.1; 10.6), role functioning (7.2, 1.3; 13.1) and social functioning (5.9, 0.2; 11.6)) and depression (PHQ9 (-1.16, -2.19; -0.13)). In high-fatigued patients, exercise did show significant positive effects on objective cognitive function (ACS Reaction Time (-26.8, -52.9; -0.6) and ACS Wordlist Learning (4.4, 0.5; 8.3)). Conclusions: A 6-month exercise intervention did not improve objectively measured cognitive function in chemotherapy-exposed BC patients with cognitive problems. However, self-reported cognitive function, physical fitness, fatigue, QoL and depression did improve. Unplanned analysis indicated a small positive effect of exercise on cognitive functioning in high-fatigued patients. Clinical trial information: NTR6104.

Cross-cultural adaptation, reliability, and validity of the Turkish version of the Cancer Fatigue Scale in patients with breast cancer

Background/aim: The Cancer Fatigue Scale (CFS) was developed to evaluate the severity of fatigue in patients with breast cancer. The aim of this study is to translate and culturally adapt a Turkish version and investigate the validity and reliability of the CFS in Turkish patients with fatigue symptoms. Materials and methods: Eighty participants completed the Turkish version of the CFS for breast cancer and the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire ″Core 30″ (EORTC QLQ-C30). Test-retest reliability was evaluated by repeating the CFS with a 7-day interval. Results: The CFS demonstrated high test-retest reliability (ICC = 0.95) and good internal consistency (Cronbach′s alpha = 0.74) for all domains. The Kaiser-Meyer-Olkin measure of sampling adequacy was found to be 0.819, which is considered to be satisfactory (>0.5). Correlations between domains of CFS physical and EORTC physical (r: 0.77), CFS cognitive and EORTC cognitive (r: 0.70), and CFS physical and EORTC fatigue (r: 0.80) were found to be significant. Conclusion: The Turkish version of the CFS is a reliable and valid instrument to assess physical, effective, and cognitive dimensions of fatigue. The CFS may be used to evaluate the severity of fatigue in Turkish-speaking breast cancer patients.

Could Objective Tests Be Used to Measure Fatigue in Patients With Advanced Cancer?

ContextAssessment of cancer-related fatigue is currently based on patient-reported outcomes. We asked whether objective assessments, such as muscle strength and nutritional markers, can be used as surrogate measures of cancer-related fatigue. ObjectiveWe examined the association among three fatigue scales, muscle strength, and nutritional markers in patients with advanced cancer. MethodsIn this prospective study, we enrolled hospitalized cancer patients who had been seen in palliative care consultation at MD Anderson Cancer Center. We assessed fatigue using three fatigue scales—the Brief Fatigue Inventory (BFI), the Edmonton Symptom Assessment System (ESAS), and the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30)—and determined their association with objective assessments, including handgrip strength, maximal inspiratory pressure, lean body mass, phase angle, and albumin. Spearman's correlation test was used to assess associations. ResultsAmong 222 patients, the mean age was 55 years; 59% were women. The median overall survival was 106 days. The total BFI score had weak association with handgrip strength (ρ = −0.18, P = 0.007) and no association with the remaining objective measures. ESAS fatigue and EORTC fatigue showed similar findings. Total BFI had moderate-to-strong association with ESAS (ρ = 0.54, P < 0.0001) and EORTC (ρ = 0.60, P < 0.0001) fatigue. ConclusionOur study showed that subjective assessment of fatigue based on patient-reported outcomes correlates only weakly with muscle strength and nutritional markers; thus, patient-reported outcomes remain the gold standard for fatigue assessment.

Patient Related Factors Have an Indepedent Impact on Overall Survival in Myelodysplastic Syndrome Patients: A Report of the MDS-Can Registry

Introduction: MDS is a disease of the elderly; yet, the impact of clinical frailty (an age-related vulnerability state created by a multidimensional loss of reserves) and patient-reported outcomes on overall survival (OS) are unknown. Rockwood et al. have developed a simple 9-point clinical frailty scale (CFS) that correlated highly with the risk of death, institutionalization, worsening health and hospital use (Rockwood K., CMAJ 2005). In a prospective, national MDS registry, participants have undergone annual evaluations with the following: (a) 3 geriatric physical performance tests, (b) Charlson (CCI) and Della Porta comorbidity index (DP-CCI) scores, (c) graded frailty using the Rockwood CFS, (d) disability assessments with the Lawton Brody SIADL, and (e) QOL using the EORTC QLQ C-30 and the EQ-5D. The results of these frailty assessments and the effects of these patient-related factors and reported outcomes on OS, in addition to the IPSS/revised IPSS, will be presented. Methods: Overall survival was measured from time to enrollment. Results from physical performance tests were divided into quintiles with higher scores indicating better performance. We used univariate and multivariable Cox proportional hazard model to determine significant predictive factors of overall survival (OS). The variables considered included age, IPSS, R-IPSS, ferritin, LDH, transfusion dependence, hemoglobin (hgb), ECOG, frailty, CCI and DP-CCI, grip strength, 4 M walk test, stand-sit test, modified short physical performance battery (SPPB), Lawton Brody SIADL, time from diagnosis and selected QOL domains including the EQ-5D summary score, EORTC physical functioning, dyspnea and fatigue scores. Results: 453 MDS patients (pts) have been consented and enrolled locally since January 2008 (n=231) and nationally since January 2012 (n=222). Median time from diagnosis was 5.8 mos (IQR 1.4-21). Median age was 73 y (range, 26-95 y), 65% were male and the R-IPSS scores were very low (14%), low (46%), intermediate (24%), high (10%) and very high (6%). Thirty-three % of pts were transfusion dependent at enrollment. Median CCI and DP-CCI scores were 1 (0-12) and 0 (0-6) respectively with 18% and 24% falling into the highest category scores. Median frailty scale score (n=346) was 3 (1-9) with 25% having scores indicating moderate (4-5) or severe (6-9) frailty. The CCI and DP-CCI strongly correlated (r=0.6; p< .0001) with each other, while frailty significantly but modestly correlated with them (r=0.3-0.35, p<.0001). With a median follow up (from enrollment) of 15 mos (95% CI: 13-16), 159 (35%) pts have died and 28 pts lost to follow up. Actuarial survival was 41.0 mos (range, 33.6 - 48.5 mos). When considering patient related factors - age, frailty, comorbidity (both indices), sex, ECOG, the 10 x stand sit test, the SPPB, Lawton Brody SIADL, and all QOL domains considered above were significantly predictive of OS. The multivariable model with the highest R2 included R-IPSS (p=.0004), frailty (1-3 vs 4-9, p= .004), CCI (0-1 vs >2, p=.03) and EORTC fatigue (p=.01) as summarized in Table 1 below. A frailty score > 3 predicted for worse survival (figure 1: 2 year OS 68.5% vs. 83.8%) and further refined survival within the R-IPSS categories (Figure 2). Frailty was also the single most predictive factor for OS from the start of azacitidine therapy (not shown). Conclusions: Patient-related factors such as frailty and comorbidity (that evaluate physiologic reserve and global fitness) should be considered in addition to traditional MDS prognostic indices.Abstract 165. TableIndependent CovariatePredictive factors at baselineCoefficientSEp-valueHR95% CI of HRR2 (%)Time from diagnosis (months) *0.03350.10760.75571.0340.8371.27717.29%R-IPSS (5 categories)<.0001Very high vs. very low2.57010.72890.000413.0663.13154.524High vs. very low2.11560.64370.00108.2942.34929.285Intermediate vs. very low1.04660.64300.10362.8480.80810.043Low vs. very low0.63460.61810.30451.8860.5626.334Frailty (1-3 vs. 4-9)-0.83230.29050.00420.4350.2460.769Comorbidity Charlson (0-1 vs. ³2)-0.59150.27490.03140.5530.3230.949EORTC fatigue *0.36710.15460.01761.4431.0661.954natural log-transformation was applied for normalizing distribution [Display omitted] [Display omitted] DisclosuresBuckstein:Celgene Canada: Research Funding. Wells:Celgene: Honoraria, Other, Research Funding; Novartis: Honoraria, Research Funding; Alexion: Honoraria, Research Funding. Leitch:Alexion: Honoraria, Research Funding; Novartis: Honoraria, Research Funding, Speakers Bureau; Celgene: Educational Grant Other, Honoraria, Research Funding. Shamy:Celgene: Honoraria, Other.

Post-surgical highly sensitive C-reactive protein (hsCRP) and prognosis in early stage in breast cancer (BC).

550 Background: Obesity, commonly associated with inflammation, is associated with poor prognosis in BC. Previous research suggests CRP, an obesity-associated marker of systemic inflammation, may mediate the adverse prognostic effects of obesity and be associated with fatigue. We examined the association of hsCRP with obesity-related factors, fatigue and distant disease-free and overall survival (DDFS, OS) in an early BC cohort. Methods: 501 non-diabetic women with T1-3, N0-1, M0 BC diagnosed 1989-96 provided fasting blood (mean 7.7 ± 4.3 weeks after surgery, prior to systemic therapy, stored at -80°C) which was analyzed for hsCRP (Roche Elecsys immunochemistry). 359 women also completed the EORTC QLQ-C30 (mean 8 ± 3.9 weeks post-surgery). Women were followed prospectively to 2007. Data were analyzed using Spearman's rank correlation coefficients (r) and Cox models. Results: Mean age was 50.5 ± 9.7 years; 282/159/24/36 subjects had T1/T2/T3/TX cancers; 350 were N0; 306 had ER+ and 278 PgR+ cancers (HER2 was not performed); 76/208/142 cancers were grade 1/2/3; adjuvant treatment involved radiation (369 subjects), chemotherapy (196), tamoxifen (107). Median hsCRP was 0.9 mg/L (25th/75th percentiles: 0.4/2.4 mg/L). hsCRP was correlated (all p &lt; 0.0001) with age (r = 0.25), Body Mass Index (BMI, r = 0.6), insulin (r = 0.44), Homeostasis Model Assessment (r = 0.45) and leptin (r = 0.54), but not with EORTC fatigue (r = 0.02), T or N stage, grade or ER/PgR status (any + vs. both -). Median follow-up was 12 years. hsCRP was not associated with DDFS or OS in univariate analyses (Q4 vs. Q1 HR 1.03, 95% CI 0.69-1.52, p = 0.9 and HR 1.27, 95% CI 0.86-1.86, p = 0.24 respectively) or multivariate analyses adjusting for age, T, N, grade, ER/PgR status, treatment (HR 1.02, 95% CI 0.66-1.59, p = 0.93 and HR 1.17, 95% CI 0.76-1.81, p = 0.48 respectively). Conclusions: hsCRP (measured post-op, prior to systemic therapy) was associated with age, BMI and obesity associated physiologic factors; it was not associated with fatigue, DDFS or OS. Funded by The Breast Cancer Research Foundation (New York), The Canadian Cancer Society Research Institute (formerly The Canadian Breast Cancer Research Initiative).

PD04-09: Self-Reported Cognitive Attributes and Fatigue Improve over Long-Term Follow-Up in Breast Cancer Survivors; Some Cognitive Attributes Are Worse in Breast Cancer Survivors Than in Non-Cancer Controls.

Abstract Background: Cognitive deficits and fatigue have been reported in breast cancer (BC) patients undergoing a variety of treatments, including chemotherapy; in some studies these concerns persist after completion of treatment. We examined these factors over time (median 11 yrs) in a longitudinal study of BC patients and compared the status of long-term BC survivors to non-BC controls. Methods: 535 T1-3, N0-1, M0 BC patients were enrolled 1989–96; 260 women survived without metastases to participate in long-term follow-up (LTFU) measurements in 2006–8. 161 controls without BC were enrolled 2007–8. Questionnaires examined a range of QOL attributes; here we focus on items related to cognition and fatigue including: EORTC QLQ C30 (cognitive functioning, fatigue), Profile of Mood States (POMS — confusion/bewilderment, fatigue/inertia, vigor/activity), Fatigue Symptom Inventory (FSI — average fatigue past week, total disruption index), Everyday Problems (EDP — forgetfulness, difficulty concentrating, easily distracted). 166 of the BC patients had also completed EORTC and POMS at diagnosis and 1 year, and change in items on these questionnaires was calculated. Age and income adjusted differences between BC (LTFU) and controls were analyzed. Clinical significance was defined as ≥5% of the scale range or an effect size of ≥0.2 and statistical significance as P≤ 0.05. Results: BC cases were older than controls (62.3 vs 59.1 yr), had lower education (24.6 vs 10.2% high school only) and family income (38.2 vs 19.8% &amp;lt; $60,000 annually) (all P&amp;lt;0.01). Cognitive attributes: BC patients showed clinically and statistically significant improvements between diagnosis and LTFU on POMS confusion/bewilderment but not EORTC cognitive functioning. Comparing BC (LTFU) to controls, in multivariate analyses adjusted for age and income, EORTC cognitive functioning (81.5 vs 87.4) and EDP forgetfulness (0.9 vs 0.6) were clinically and statistically significantly worse in BC patients than controls. In contrast, POMS confusion/bewilderment, EDP difficulty concentrating and EDP easily distracted scores were similar in BC patients at LTFU and controls. Fatigue: BC patients showed clinically and statistically significant improvements between diagnosis and LTFU on EORTC fatigue, POMS fatigue/inertia and POMS vigor/activity. After adjustment for age and income there were no clinically and statistically significant differences between BC (LTFU) and controls on any fatigue items. Conclusions: Fatigue items, as well as some cognitive items, improved over time in BC patients and scores were comparable to scores in non-BC controls at LTFU. However, scores on some cognitive items were worse in LTFU BC patients than in non-BC controls raising concerns that BC diagnosis and treatment may be associated with long-term adverse effects on some aspects of self-reported cognitive attributes. (Funded by The Breast Cancer Research Foundation) Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD04-09.

Psychological distress and fatigue predicted recurrence and survival in primary breast cancer patients

This study examined whether psychological distress in newly diagnosed breast cancer patients was associated with their survival. We analyzed data from 1,588 breast cancer patients who filled in the EORTC QLQ-C30 questionnaire and the Hospital Anxiety and Depression Scale (HADS) 2 months after their primary operation. The median follow-up time was 12.9 years. Psychological distress (EORTC QLQ-C30 emotional function; HADS anxiety; HADS depression) and EORTC fatigue, physical function, and overall ratings were used to predict recurrence-free and overall survival, controlling for the known clinical and histopathological prognostic factors (biological model) using Cox multivariate regression analysis. Low levels of psychological distress (good EORTC emotional function) and low fatigue independently predicted longer recurrence-free and overall survival, controlling for biological factors. Lack of anxiety (HADS) also predicted longer recurrence-free survival. When added in combination to the biological model, fatigue remained a significant predictor of recurrence-free survival (P = 0.0004; risk ratio 1.32 (1.13-1.54)) and emotional function remained a significant predictor of overall survival (P = 0.0074; risk ratio 0.81 (0.70-0.95)). Low psychological distress and a low level of fatigue may cause a greater cancer resistance or may reflect underlying mental and physical robustness.

Identifying optimal cutpoints for quality of life function in patients with advanced cancer

8139 Background: Substantial resources have been spent to develop validated quality of life (QoL) tools in cancer. However, few hospitals in the US routinely utilize QoL measures to develop treatment plans in patient care. Indeed, to our knowledge, our center is the only hospital-based oncology program in the US that routinely collects QoL data on patients not participating in clinical trials. We used survival analysis to determine if we could convert continuous scales of QoL data into categorical prognostic outcomes. Methods: Baseline QoL data were collected from 310 patients treated at our center between 04/01 and 10/03. 2 QoL tools were used: Ferrans and Powers Quality of Life Index (QLI), which has 4 functional domains, and EORTC QLQ-C30, which has 5 functional domains and 9 symptom items. Using the Wilcoxon test, differences in survival were measured in serial increments of 10 points for EORTC and 3 points for QLI (these levels are associated with significant improvement in QoL). Results from Wilcoxon test were plotted as a function of QoL cutoff points. Linear and polynomial solutions were fitted and Wald statistic identified the best fit. Results: Of 310 patients, 180 were females and 130 males, with a median age of 55 years (range 21 - 82). 64.2% had failed prior treatment. Most common cancers were breast (25%), colorectal (23.3%), and lung (17.7%). Statistical analysis indicated that Health and Function Domain (Wald Test P = 0.0194) had two cutpoints at values 10 and 20. We found a statistically significant difference in survival between patients with scores < 10, 10 to 20, and > 20, the median survival being 169, 349, and 692 days respectively (p < 0.0001). Similarly, EORTC fatigue item (Wald Test P = 0.022) has two cutpoints at values 35 and 80. The median survival of patients with scores < 35, 35 to 80, and > 80 were 450, 413, and 129 days respectively (p < 0.0001). Conclusions: The transformation of a QoL research tool into a clinical management tool is a challenge. As an initial step, we showed that we could produce categorical survival outcome categories from QoL data in 310 patients with advanced cancer. The next step is to refine this analysis to produce discrete outcome categories that will facilitate physician thinking on treatment planning. No significant financial relationships to disclose.