Potential therapeutic effect of a ketogenic diet for the treatment of lymphoedema: Results of an exploratory study.

BACKGROUND: Lymphoedema is a chronic and progressive disease characterised by excessive accumulation of lymph in the interstitial compartment, leading to tissue swelling and fibroadipose deposition. Lymphangiogenesis is partly regulated by ketone body oxidation, and a ketogenic diet (KD) has shown therapeutic efficacy in a preclinical mouse tail lymphoedema model. Therefore, we aimed to investigate the potential therapeutic effect of a KD in patients with secondary lymphoedema. METHODS: Nine patients with unilateral stage 2 lymphoedema secondary to lymphadenectomy were included in this quasi-experimental exploratory study consisting of a short run-in phase to gradually induce ketosis, followed by a classic KD (CKD) and modified Atkins diet (MAD) phase during which patients consumed a CKD and MAD, respectively. Lymphatic function and oedema volume, the primary outcomes, were assessed at baseline and at the end of both the CKD and MAD phase. Secondary outcomes included health-related and lymphedema-specific quality of life (QoL). RESULTS: Seven out of nine patients completed the study protocol. Lymphatic function was improved upon consumption of both a CKD (dermal backflow score [mean ± SD]: 7.29 ± 2.98 vs. 10.86 ± 2.19 at baseline; p = 0.03) and MAD (6.71 ± 2.06; p = 0.02), whereas oedema volume did not decrease during the course of the study (excess limb volume [mean ± SD]: 20.13 ± 10.25% at end of CKD and 24.07 ± 17.77% at end of MAD vs. 20.79 ± 12.96% at baseline; p > 0.99 and p > 0.30, respectively). No changes were observed in health-related, nor lymphoedema-specific QoL at the end of CKD and MAD. CONCLUSIONS: The consumption of a KD improved lymphatic function and was associated with a clinically meaningful reduction in oedema volume in some patients (3/7 at end of CKD, 2/7 at end of MAD) with unilateral stage 2 secondary lymphoedema. These results highlight the potential of a KD to improve lymphatic function in patients with lymphoedema. However, further studies are required to substantiate our findings.

Upper-Limb Movement Quality before and after Surgery in Women with Breast Cancer: An Exploratory Study.

(1) Background: This study aimed to describe upper-limb (UL) movement quality parameters in women after breast cancer surgery and to explore their clinical relevance in relation to post-surgical pain and disability. (2) Methods: UL movement quality was assessed in 30 women before and 3 weeks after surgery for breast cancer. Via accelerometer data captured from a sensor located at the distal end of the forearm on the operated side, various movement quality parameters (local dynamic stability, movement predictability, movement smoothness, movement symmetry, and movement variability) were investigated while women performed a cyclic, weighted reaching task. At both test moments, the Quick Disabilities of the Arm, Shoulder, and Hand (Quick DASH) questionnaire was filled out to assess UL disability and pain severity. (3) Results: No significant differences in movement quality parameters were found between the pre-surgical and post-surgical time points. No significant correlations between post-operative UL disability or pain severity and movement quality were found. (4) Conclusions: From this study sample, no apparent clinically relevant movement quality parameters could be derived for a cyclic, weighted reaching task. This suggests that the search for an easy-to-use, quantitative analysis tool for UL qualitative functioning to be used in research and clinical practice should continue.

Accuracy of consumer-based activity trackers as measuring tool and coaching device in breast and colorectal cancer survivors.

PURPOSE: Consumer-based activity trackers are used to measure and promote PA. We studied the accuracy of a wrist- and waist-worn activity tracker in cancer survivors and compared these results to a healthy age-matched control group. METHODS: Twenty-two cancer survivors and 35 healthy subjects wore an activity tracker at the waist and at the wrist combined with a reference activity monitor at the waist (Dynaport Movemonitor). The devices were worn for 14 consecutive days. The mean daily step count from both activity trackers was compared with the reference activity monitor to investigate accuracy and agreement (paired t-test, intraclass correlation, Bland-Altman plots). To evaluate the accuracy as a coaching tool, day-by-day differences within patients were calculated. The Kendall correlation coefficient was used to test the consistency of ranking daily steps between the activity trackers and the reference activity monitor. RESULTS: The wrist-worn wearable significantly overestimated the daily step count in the cancer group (mean ± SDΔ: + 1305 (2685) steps per day; p = 0.033) and in the healthy control group (mean ± SDΔ: + 1598 (2927) steps per day; p = 0.003). The waist-worn wearable underestimated the step count in both groups, although this was not statistically significant. As a coaching device, moderate (r = 0.642-0.670) and strong (r = 0.733-0.738) accuracy was found for the wrist- and waist-worn tracker, respectively, for detecting day-by-day variability in both populations. CONCLUSION: Our results show that wrist-worn activity trackers significantly overestimate daily step count in both cancer survivors and healthy control subjects. Based on the accuracy, in particular, the waist-worn activity tracker could possibly be used as a coaching tool.

Returning to Work After Breast Cancer Surgery: A Randomised Controlled Trial on the Effect of Pain Neuroscience Education.

PURPOSE: The aim of this study was to investigate the effect of pain neuroscience education compared to biomedical pain education after breast cancer surgery on (1) work status, (2) time until work resumption, and (3) change in return-to-work expectations up to 18 months post-surgery. METHODS: Participants were randomly assigned to either pain neuroscience education (intervention group) or biomedical pain education (control group) in addition to a standard physical therapy program after surgery for breast cancer. The first four months following surgery, one to two physiotherapy sessions and three educational sessions were scheduled. After, two educational sessions and two physiotherapy sessions were held at six and eight months postoperatively. All outcomes were assessed at four, six, eight, 12 and 18 months postoperatively. RESULTS: At 12 months, in the intervention group, 71% of the women returned to work compared to 53% in the control group (18% points difference, 95%CI:-0.1 to 35;p = 0.07). At 18 months, the differences decreased to 9% points, 95%CI:-26 to 7;p = 0.35). Neither time until work resumption (p = 0.46) nor change in estimation of own ability to return to work up to 18 months postoperatively (p = 0.21) significantly differed between both groups. CONCLUSION: No significant differences were found regarding return to work outcomes between women receiving pain neuroscience education versus biomedical pain education after breast cancer surgery. Further research is warranted to explore the potential role of pain neuroscience education in return-to-work interventions following breast cancer surgery.

Assessing Upper Limb Function in Breast Cancer Survivors Using Wearable Sensors and Machine Learning in a Free-Living Environment.

(1) Background: Being able to objectively assess upper limb (UL) dysfunction in breast cancer survivors (BCS) is an emerging issue. This study aims to determine the accuracy of a pre-trained lab-based machine learning model (MLM) to distinguish functional from non-functional arm movements in a home situation in BCS. (2) Methods: Participants performed four daily life activities while wearing two wrist accelerometers and being video recorded. To define UL functioning, video data were annotated and accelerometer data were analyzed using a counts threshold method and an MLM. Prediction accuracy, recall, sensitivity, f1-score, 'total minutes functional activity' and 'percentage functionally active' were considered. (3) Results: Despite a good MLM accuracy (0.77-0.90), recall, and specificity, the f1-score was poor. An overestimation of the 'total minutes functional activity' and 'percentage functionally active' was found by the MLM. Between the video-annotated data and the functional activity determined by the MLM, the mean differences were 0.14% and 0.10% for the left and right side, respectively. For the video-annotated data versus the counts threshold method, the mean differences were 0.27% and 0.24%, respectively. (4) Conclusions: An MLM is a better alternative than the counts threshold method for distinguishing functional from non-functional arm movements. However, the abovementioned wrist accelerometer-based assessment methods overestimate UL functional activity.

The Role of Pelvic Floor Muscle Training on Low Anterior Resection Syndrome: A Multicenter Randomized Controlled Trial.

BACKGROUND AND OBJECTIVE: Total mesorectal excision (TME) for rectal cancer (RC) often results in significant bowel symptoms, commonly known as low anterior resection syndrome (LARS). Although pelvic floor muscle training (PFMT) is recommended in noncancer populations for treating bowel symptoms, this has been scarcely investigated in RC patients. The objective was to investigate PFMT effectiveness on LARS in patients after TME for RC. METHODS: A multicenter, single-blind prospective randomized controlled trial comparing PFMT (intervention; n=50) versus no PFMT (control; n=54) 1 month following TME/stoma closure was performed. The primary endpoint was the proportion of participants with an improvement in the LARS category at 4 months. Secondary outcomes were: continuous LARS scores, ColoRectal Functioning Outcome scores, Numeric Rating Scale scores, stool diary items, and Short Form 12 scores; all assessed at 1, 4, 6, and 12 months. RESULTS: The proportion of participants with an improvement in LARS category was statistically higher after PFMT compared with controls at 4 months (38.3% vs 19.6%; P =0.0415) and 6 months (47.8% vs 21.3%; P =0.0091), but no longer at 12 months (40.0% vs 34.9%; P =0.3897). Following secondary outcomes were significantly lower at 4 months: LARS scores (continuous, P =0.0496), ColoRectal Functioning Outcome scores ( P =0.0369) and frequency of bowel movements ( P =0.0277), solid stool leakage (day, P =0.0241; night, P =0.0496) and the number of clusters ( P =0.0369), derived from the stool diary. No significant differences were found for the Numeric Rating Scale/quality of life scores. CONCLUSIONS: PFMT for bowel symptoms after TME resulted in lower proportions and faster recovery of bowel symptoms up to 6 months after surgery/stoma closure, justifying PFMT as an early, first-line treatment option for bowel symptoms after RC.

Is evaluation by questionnaires sufficient to cover all aspects of bowel symptoms in rectal cancer patients after low anterior resection?

AIM: The aim of the study was to investigate whether bowel symptoms related to low anterior resection for rectal cancer can be sufficiently well evaluated by the Low Anterior Resection Syndrome (LARS) questionnaire score or the ColoRectal Functional Outcome (COREFO) questionnaire compared with a stool diary. METHOD: All patients underwent low anterior resection for rectal cancer. They were asked to fill out a stool diary, the LARS questionnaire and the COREFO questionnaire, at 1, 4, 6 and 12 months after low anterior resection or stoma closure. The main outcome measure was the amount of association (calculated by means of canonical correlation analysis) between items on anal incontinence for faeces, frequency of bowel movements, clustering of bowel movements, urgency and soiling. RESULTS: Ninety-five patients were included. Items on anal incontinence for faeces and frequency of bowel movements were significantly correlated between the LARS questionnaire or the COREFO questionnaire, versus the stool diary, respectively. Items on soiling were significantly correlated between the COREFO questionnaire and the stool diary. CONCLUSION: Although the LARS questionnaire and the COREFO questionnaire are reliable and valid for measuring low anterior resection syndrome after rectal cancer, our results show that there are no strong associations with the stool diary. Therefore, we can conclude that there is additional clinical information to be obtained from the stool diary. In order to evaluate all aspects of low anterior resection syndrome, we suggest the addition of a stool diary or a combination of different measurement methods during patient follow-up.

Biopsychosocial risk factors for pain and pain-related disability 1 year after surgery for breast cancer.

PURPOSE: Knowledge regarding risk factors for pain in the long term after surgery for breast cancer may be of great value in preventing this prevalent and debilitating side effect. Despite the biopsychosocial nature of pain, the predictive value of both pre- and postoperative biopsychosocial functioning for long-term pain intensity and pain-related disability has not yet been studied. METHODS: One hundred sixty-six women planned for unilateral breast cancer surgery were included in this prospective cohort study. Pre- and postoperative outcomes related to pain, psychosocial, and somatosensory functioning (questionnaires and quantitative sensory testing) were evaluated as risk factors for pain intensity (visual analog scale) and pain-related disability (pain disability index) 1 year after surgery for breast cancer. Both bivariable and stepwise linear regression analyses were performed. RESULTS: The most consistent biopsychosocial risk factors were symptoms related to altered central somatosensory functioning (central sensitization inventory), psychological symptoms, and social support (psychological symptoms and support subscale of McGill Quality of Life Questionnaire). Results also showed that a pre- and postoperative disturbed functioning of the somatosensory nervous system in the surgical area could provide additional information regarding pain intensity or pain-related disability in the long term after surgery for breast cancer. CONCLUSION: This study revealed several biopsychosocial characteristics that might be used to identify women more vulnerable to have pain and pain-related disability in the long term after surgery for breast cancer, allowing for more effective pain management and prevention.

Pain prevalence and characteristics in survivors of solid cancers: a systematic review and meta-analysis.

PURPOSE: The latest systematic review on the prevalence of pain in cancer survivors was published 5 years ago. The current review aims to provide an extended overview on the prevalence of pain, pain mechanisms, pain characteristics, and assessment methods in cancer survivors. METHODS: A systematic research was conducted on 17th of April 2020 using MEDLINE, Embase, Scopus, Web of Science, and Cochrane looking at studies from 2014 to 2020. Studies had to report pain prevalence rates in cancer survivors with a solid tumor who finished curative treatment at least 3 months ago. Methodological quality was assessed by two independent reviewers using the Joanna Briggs Institute quality appraisal tool. Characteristics of the included studies, participants and reported pain prevalence rates were extracted. The reported prevalence rates of the individual studies were pooled within a meta-analysis. Meta-regressions were performed to identify possible determinants of the pooled pain prevalence. RESULTS: After deduplication, 7300 articles were screened, after which 38 were included in the meta-analysis. Risk of bias was rated low in 26 articles and moderate in 12 articles. The pooled pain prevalence was 47% (95%CI 39-55), with a heterogeneity of 98.99%. CONCLUSION: This meta-analysis suggests that nearly half of cancer survivors report pain after completing curative treatment at least 3 months ago. However, substantial unexplained heterogeneity warrants cautious interpretation of these results. Meta-regression using cancer type, treatment location, pain measurement, and follow-up time as a covariate could not explain influencing factors explaining the high heterogeneity.

Absolute and Relative Reliability of a Comprehensive Quantitative Sensory Testing Protocol in Women Treated for Breast Cancer.

OBJECTIVE: Quantitative sensory testing (QST) consists of noninvasive psychophysical assessment techniques to evaluate the functioning of the somatosensory nervous system. Despite the importance of reliability for the correct use of QST results in research and clinical practice, the relative and absolute intra- and inter-rater reliability of a comprehensive QST protocol to evaluate the functioning of both the peripheral and central somatosensory nervous system in a breast cancer population has not yet been investigated. SETTING: University Hospitals, Leuven, Belgium. SUBJECTS: Thirty women at least 6 months after unilateral breast cancer surgery. METHODS: The protocol included nine static and dynamic QST methods (mechanical pain-detection thresholds, pressure pain thresholds, thermal pain-detection thresholds for heat and cold, temporal summation, and conditioned pain modulation [CPM]) performed in the surgical area and in more distant regions. Absolute and relative intra-rater reliability (60-minute interval) and inter-rater reliabilty (1-week interval) were evaluated with intraclass correlation coefficients, standard error of measurement, and Bland-Altman plots. RESULTS: Moderate to excellent relative intra-rater reliability and inter-rater reliability were found for the evaluation of mechanical thresholds, pressure pain thresholds, and temporal summation. The reliability of the CPM paradigm was considered weak. Systematic bias between raters was noticed for the detection of mechanical and cold stimuli at the non-affected trunk and for CPM. CONCLUSIONS: Except for the evaluation of CPM, the QST protocol was found suitable for identifying differences between subjects (relative reliability) and for individual follow-up after breast cancer surgery (limited systematic bias) during a 1-week time frame. Additional research is required to determine the measurement properties that influence CPM test stability to establish a more reliable CPM test paradigm.

Can the CutiScan CS 100® measure anisotropy and viscoelasticity in scar tissue after mastectomy? A reliability and validity study.

BACKGROUND: Scars have different biomechanical characteristics, including anisotropy and viscoelasticity compared to healthy skin. To assess these characteristics, the CutiScan CS 100® can be used. The aim of the present study is to investigate reliability and validity of this device in breast cancer patients. MATERIALS AND METHODS: Thirty female patients, with scar adhesions following mastectomy were assessed with the CutiScan CS 100® . Maximal distensibility (pixels) (V1), after-suction return rate (pixels) (V2), and their ratio (%) (V3) at three points on and around the scar were assessed as measures of viscoelasticity. For intra- and interrater reliabilities, the intra-class correlation coefficient (ICC) and its 95% confidence intervals were calculated. The standard error of measurement (SEM) was calculated to interpret reproducibility of these measurements. To investigate criterion validity of the measurement of anisotropy, measurements in the direction of healthy skin were compared with measurements in the direction of the scar, using a paired t-test. RESULTS: V1, V2, and V3 show poor to moderate intrarater reliability (ICC 0.00-0.72) and interrater reliability (ICC 0.00-0.53). The maximum displacement (V1) on the measurement point above the scar shows the best reliability (ICC 0.33-0.72). The SEM is about the same for all parameters at all three points. The paired sample t-test showed a significant difference (p < 0.05) between V1 in the direction towards the scar versus the measurement towards healthy tissue, on the point below the scar. CONCLUSION: These first reliability and validity results of the CutiScan CS 100® for measuring anisotropy and viscoelasticity in scar tissue adhesions after mastectomy seem promising. Further research is needed addressing the limitations of the present study design.

Breast cancer-related lymphedema and its treatment: how big is the financial impact?

PURPOSE: Decongestive lymphatic treatment (DLT) is still the gold standard for treatment of breast cancer-related lymphedema (BCRL). With up to 17% of the patients treated for breast cancer developing BCRL, this morbidity imposes a tremendous financial burden for patients and society. Knowledge about this economic burden related to BCRL and its conservative treatment in a European setting is lacking. The aim of this prospective, longitudinal cohort study was to estimate the direct healthcare costs related to BCRL and its treatment in a European setting. METHODS: Patients with BCRL were treated with DLT consisting of an intensive treatment phase of 3 weeks, followed by a maintenance treatment phase of 6 months. Additionally, the follow-up period comprised 6 months. During these 3 weeks and 12 months, all direct costs associated with the treatment of BCRL and its sequelae were documented through billing prices and a self-developed questionnaire which was administered after the intensive treatment phase, and subsequently 3-monthly during the entire period. RESULTS: A total of 194 patients were enrolled in this study. Of these, 17% (n = 32) showed lymphedema stage I, 56% (n = 109) had lymphedema stage IIa, and 27% (n = 53) had lymphedema stage IIb. Total direct healthcare costs per patient were €2248.93 on average during the entire period of 3 weeks of intensive treatments and 12 months of maintenance decongestive therapy. Within these mean direct costs, €1803.35 (80%) was accounted for statutory health insurances, and €445.58 (20%) was out-of-pocket expenses for patients. CONCLUSION: This study is one of the first standardized high-quality health economic analyses of BRCL treatment in Europe. The present study indicates that the price tag of BCRL treatment in Belgium is high not only for the health insurance but also for the patients Clinical trial registration number The study makes part of a double-blind, multi-center, randomized controlled trial (EFforT-BCRL trial), which is registered in clinicaltrials.gov (NCT02609724). CME reference S58689, EudraCT Number 2015-004822-33.

Self-reported signs and symptoms of secondary upper limb lymphoedema related to breast cancer treatment: Systematic review.

INTRODUCTION: Breast cancer survivors with secondary upper limb lymphoedema (ULL) may report a wide range of self-reported symptoms. At the moment, no overview of ULL-specific symptoms is available. The first aim, therefore, was to compare the prevalence rates of self-reported signs and symptoms in people with and without secondary ULL due to breast cancer treatment. The second aim was to determine whether symptoms of lymphoedema could be predictive for the development of ULL. The third aim was to describe the association between the presence/severity of symptoms and the presence/severity of ULL. METHODS: A systematic search was conducted in Medline, Scopus, CINAHL and EMBASE databases, with key words related to breast cancer, symptoms and ULL. RESULTS: Twenty-nine articles were eligible. The most frequently reported signs and symptoms were swelling (80.9%) and heaviness (66.7%) in the ULL group and tenderness (37%) and numbness (27%) in the non-ULL group. Perceived larger arm size, as well as feelings of arm tightness, stiffness, puffiness, pain, sensory disturbances and functional changes were predictive for the development of ULL. Moderate correlations were found between the presence of swelling, firmness in the past year and tightness now and severity of ULL. There was also moderate correlation between the presence of swelling and heaviness now and the presence of ULL. CONCLUSIONS: Swelling and heaviness are the most commonly reported symptoms in patients with ULL. The presences of these two symptoms are moderately correlated with the presence and/or severity of ULL. Although limited information regarding the predictive self-reported symptoms for the development of ULL was found. Further research with standardised definitions of ULL and validated questionnaires for self-reported signs and symptoms are needed to confirm which signs and symptoms are related to ULL and which to other upper limb morbidities.

Physical activity levels after low anterior resection for rectal cancer: one-year follow-up.

BACKGROUND: Overall survival rates after rectal cancer have increased. Therefore, functional outcomes rightly deserve more interest. The aims of this study were to assess progression in total, sports, occupational and household physical activity levels of rectal cancer survivors, from preoperatively to 12 months after surgery/stoma closure and to explore predictive factors. METHODS: Multi-center prospective study with 125 patients who underwent low anterior resection for rectal cancer. The Flemish Physical Activity Computerized Questionnaire was completed concerning all physical activity levels at baseline (past preoperative year) and at 1, 4, 6 and 12 months after surgery/stoma closure. At these timepoints, questionnaires (LARS-/ COREFO-questionnaire) regarding bowel symptoms were also filled out. Results were analyzed using linear mixed models for repeated measures. RESULTS: Total physical activity levels up to 12 months remained significantly lower than preoperative. Occupational and sports physical activity levels remained significantly lower until 6 and 4 months postoperative, respectively. Predictive factors for decreased physical activity levels at a specific timepoint were: younger age and no stoma (total physical activity, 1 month), low/mid rectal tumor, no stoma, non-employed status (total, 4 months), higher COREFO-scores (occupational, 4 months) and non-employed status (total, 12 months). At all timepoints, lower COREFO-scores were associated with higher total physical activity levels; male gender and lower educational levels with higher occupational levels; younger age, normal BMI, employed status and adjuvant therapy with higher sports levels; and female gender, lower educational level and unemployed status with higher household levels. CONCLUSIONS: One year after rectal cancer treatment, total physical activity levels were still not recovered. Rectal cancer patients, especially those at risk for decreased physical activity levels and with major bowel complaints, should be identified and guided to increase their activities. TRIAL REGISTRATION: This trial has been registered at Netherlands Trial Register ( NTR6383 , 23/01/2017).

Effectiveness of perioperative pain science education on pain, psychological factors and physical functioning: A systematic review.

OBJECTIVE: To synthesize the evidence on the effectiveness of pain science education on pain, psychological factors and physical functioning in adults who underwent surgery. DATA SOURCES: A systematic literature search of English articles using PubMed/Medline, Embase, Web of Science Core Collection, and Cochrane Library. REVIEW METHODS: The search strategy was constructed as follows: (((pain) AND (education)) OR (pain education)) AND (surgery). Only controlled quantitative studies in adults reporting outcome(s) on pain, psychological factors and/or physical functioning were included. Risk of bias was assessed using the Cochrane risk of bias tools. P-values and corresponding effect sizes for interaction-effect (time × group) portrayed the difference in change over time between groups were of interest. The last search was conducted on February 28, 2021. RESULTS: Nine papers (n = 1078) were deemed eligible for this review. Two randomized controlled trials showed significant interaction effects. Breast cancer patients who had received one preoperative pain science education session showed a significant increase in postoperative pain compared to controls (P-value = 0.0394). Furthermore, psychological factors (pain catastrophizing and kinesiophobia) decreased in participants who had received pain science education before total knee arthroplasty, while this was not the case in the control group (P-value < 0.001, ƞ2p:0.11). CONCLUSIONS: Overall, pain science education did not result in any significant postoperative effects on pain, psychological factors and/or physical functioning compared to controls. There is currently no strong evidence for the implementation of pain science education in the perioperative period.Registration number: PROSPERO: ID 161267, registration number CRD42020161267.

What are the economic burden and costs associated with the treatment of breast cancer-related lymphoedema? A systematic review.

OBJECTIVES: To provide an overview of costs associated with the treatment of breast cancer-related lymphoedema (BCRL) and its possible sequelae, borne by patients or by society. DATA SOURCES: According to the PRISMA guideline, a systematic literature search was carried out in four electronic databases: PubMed, Web of Science, Cochrane Clinical Trials and EMBASE. Searches were performed on October 1, 2018. STUDY SELECTION: Eligibility criteria: (1) expenses of adults (age > 18 years), (2) concerning patients with BCRL, (3) overview of (in)direct costs associated with BCRL, (4) expenses in which at least one type of conservative treatment modality for lymphoedema is included and/or costs for hospital admissions due to infections. Reviews and meta-analyses were excluded. DATA EXTRACTION: After assessing the risk of bias and level of evidence, quantitative data on (in)direct costs for BCRL treatment during a well-mentioned timeframe were extracted. DATA SYNTHESIS: Eight studies were included. Three studies reported on patient-borne costs related to BCRL. Mean direct costs per year borne by patients ranged between USD$2306 and USD$2574. Indirect costs borne by patients ranged between USD$3325 and USD$5545 per year. Five studies estimated society-borne costs related to BCRL from claims data, billing prices and providers' services during 12 to 24 months of follow-up. Mean direct treatment costs after 1 year of decongestive lymphatic therapy (DLT) ranged between €799 (= USD$1126.60) and USD$3165. CONCLUSION: This systematic review revealed that BCRL imposes a substantial economic burden on patients and society. However, more standardized high-quality health economic analyses among this field are required. Recent economic analyses related to BCRL treatment in Europe, Asia, Africa and South America are lacking. Worldwide, further scrutiny of the economic impact of DLT for BCRL in clinical settings is needed. CLINICAL TRIAL REGISTRATION NUMBER: The review makes part of a double-blind, multi-center, randomized controlled trial (EFforT-BCRL trial), which is registered in clinicaltrials.gov (NCT02609724). CME reference S58689, EudraCT Number 2015-004822-33.

Physical activity level and age contribute to functioning problems in patients with breast cancer-related lymphedema: a multicentre cross-sectional study.

PURPOSE: Breast cancer survivors face a high risk of developing breast cancer-related lymphedema (BCRL). Besides physical symptoms such as swelling, BCRL can have a psychosocial impact and lead to problems in daily functioning. Understanding contributing variables to problems in functioning yields possibilities to improve treatment modalities and consequently patients' quality of life. Therefore, the aim of this study was to explore the association between patient-, lymphedema-, and cancer treatment-related variables with problems in functioning in patients with BCRL. METHODS: A cross-sectional study was performed in 185 patients with BCRL. Problems in daily functioning (dependent variable) were evaluated with the Lymph-ICF-UL questionnaire. Following independent variables were analysed by bi-variate and multivariable analyses, including a stepwise regression analysis: patient-related variables (age, BMI, physical activity level, education), lymphedema-related variables (excessive arm volume, duration of lymphedema, total pitting score, presence of hand edema, hardness of the tissue, lymphedema stage), and cancer treatment-related variables (type of surgery, surgery at the dominant side, radiotherapy, chemotherapy, hormone therapy, immunotherapy, TNM-classification). RESULTS: The Lymph-ICF-UL mean total score was 38% (± 21), representing a moderate amount of problems in general functioning. Multivariable regression analyses revealed that lower physical activity level and lower age are contributing factors to more problems in daily functioning. Stepwise regression analysis indicated that up to 8% of the variance in problems in functioning could be explained by physical activity level and age of patients with BCRL. CONCLUSION: Especially patients with low physical activity level and younger patients experience more problems in functioning. For the determination of certain causal interactions, future longitudinal studies including other independent variables that might explain a higher amount of problems in functioning in this population, are warranted. TRIAL REGISTRATION: The study makes part of a double-blind, multi-center, randomized controlled trial (EFforT-BCRL trial), which is registered in clinicaltrials.gov (NCT02609724). CME reference S58689, EudraCT Number 2015-004822-33.

Kinesiophobia contributes to pain-related disability in breast cancer survivors: a cross-sectional study.

PURPOSE: Pain is one of the most prevalent problems reported by breast cancer survivors. As this long-lasting complication can result in disabilities on all different domains of functioning, we aimed to clarify the contribution of different factors (pain-related factors, psychosocial factors, and fatigue) to pain-related disability in female breast cancer survivors. METHODS: Seventy women who had completed their primary breast cancer treatment were included in this cross-sectional study. The following outcome measures were evaluated as independent variables for their contribution to pain-related disability (measured by the Pain Disability Index, with a maximum score of 70): pain intensity, self-reported symptoms of central sensitization, fatigue, illness beliefs, pain catastrophizing, and kinesiophobia. At first, bi- and multivariable regression methods were conducted. Secondly, a stepwise regression analysis was performed to determine the explained variance of the PDI. RESULTS: Mean score on the PDI was 16 at 4.5 years post-surgery. Multivariable regression analysis revealed higher levels of kinesiophobia as the main contributor to pain-related disability. Ultimately, stepwise regression showed that up to 40% of variance in pain-related disability could be explained by kinesiophobia, negative perceptions related to illness consequences, and pain catastrophizing. CONCLUSION: This study shows that breast cancer survivors portray moderate self-reported pain-related disability. Kinesiophobia emerged as the main contributor to pain-related disability at this time point, which could shine a light on the improvement of treatment modalities for pain management in this population.

Reliability and validity of a Dutch Lymphoedema Questionnaire: Cross-cultural validation of the Norman Questionnaire.

OBJECTIVE: To perform the cross-cultural validation process of the Dutch Norman Questionnaire (NQ), a questionnaire for the detection and characterisation of breast-cancer related lymphoedema (BCRL) using self-reported signs and symptoms. METHODS: Test-retest reliability and construct (including convergent, divergent and known-groups validity), face and content validity were examined in breast cancer patients with (n = 30) and without (n = 30) lymphoedema. For concurrent validity, first, agreement between the diagnostic item of the NQ and a clinical diagnosis were analysed. Second, correlations between NQ scores and clinical arm volume assessment were tested. RESULTS: Test-retest reliability was found to be strong to very strong (ICC 0.79-0.96) in the lymphoedema group and moderate to very strong ( ICC 0.64-0.99) in the non-lymphoedema group. Seventeen out of 20 hypotheses on convergent and divergent validity were accepted. There was good face, content and known-groups validity as well. For concurrent validity, agreement between evaluation methods was only 0.462. Moderate correlations were found between 6 out of 9 symptom scores (r = 0.422-0.630) of the NQ and clinical assessment. CONCLUSION: The Dutch NQ is a reliable and valid questionnaire for the characterisation of BCRL using self-reported signs and symptoms. Only moderate agreement for the detection of BCRL was found.

The effectiveness of Botulinum Toxin A for treatment of upper limb impairments and dysfunctions in breast cancer survivors: A randomised controlled trial.

OBJECTIVE: To examine the effectiveness of a single Botulinum Toxin A (BTX-A) infiltration in the pectoralis major muscle, in addition to a standard physical therapy (PT) programme on upper limb impairments and dysfunctions after breast cancer treatment. METHODS: Fifty breast cancer patients with persistent pain 3 months after finishing treatment participated in a double-blinded randomised controlled trial. The intervention group received a single BTX-A infiltration. The control group received a placebo (saline) infiltration. Within one week after the infiltration, all patients attended an individual PT programme (12 sessions) during the first 3 months. Outcome parameters were active shoulder range of motion, upper limb strength, scapular statics and shoulder function. Measures were taken before the intervention, at 1, 3 (i.e. after the intervention) and 6 months follow-up. RESULTS: No differences between groups were found for all outcome parameters over the course of 6 months. However, overall beneficial effects of the PT for active forward flexion shoulder range of motion and shoulder function were found in both groups. CONCLUSION: A single Botulinum Toxin A (BTX-A) infiltration in the pectoralis major muscle, in addition to a PT programme cannot be recommended to treat upper limb impairments and dysfunctions after breast cancer treatment.