Reliability of L-Dex Scores for Assessment of Unilateral Breast Cancer-Related Lymphedema.

Objective: Breast cancer-related lymphedema (BCRL) is a common complication of breast cancer treatment that may result in swelling of the affected arm due to compromised lymphatic function. Implementing a screening program and early intervention for BCRL are important for effective management. Bioimpedance spectroscopy (BIS) is a commonly used tool for assessing BCRL. This study aimed to compare different normative ranges for BIS L-Dex scores in the detection of BCRL. Materials and Methods: Data from 158 women with clinically ascribed and indocyanine green confirmed BCRL were analysed. BIS measurements were obtained using an ImpediMed standing device, and L-Dex scores were calculated using published normative ranges for healthy individuals. Statistical analysis was performed to compare the concordance between different reference ranges in classifying individuals with lymphedema. Results: The study found that L-Dex scores calculated using different normative ranges were highly correlated and essentially interchangeable in detecting BCRL. Approximately 90% of participants exceeded the L-Dex threshold for lymphedema, with minimal discrepancies between reference ranges. False negative rates were observed in some participants, likely due to early-stage BCRL with minimal lymph accumulation. Conclusion: The findings suggest that BIS L-Dex scores are a valid indicator of BCRL, regardless of specific normative ranges used. Detection rates of clinically confirmed BCRL were consistent across different reference ranges, with minimal discrepancies. BIS remains a valuable tool for early detection and monitoring of BCRL. Future research should focus on longitudinal assessments and use of change in L-Dex scores for lymphedema monitoring and progression.

Comparison of Volume Measurements and Bioimpedance Spectroscopy Using A Stand-on Device for Assessment of Unilateral Breast Cancer-Related Lymphedema.

Objective: Breast cancer related lymphedema (BCRL) may be assessed through objective measurement of limb swelling with common techniques including volumetric measurement using a tape measure or perometry, and measurement of extracellular water using bioimpedance spectroscopy (BIS). This study aimed to evaluate the performance of a stand-on BIS device for detection of BCRL, introduce a novel graphical method to compare volumetric and BIS methods alongside traditional specificity and sensitivity analysis, and determine and compare BIS thresholds with those published previously. Materials and Methods: Female participants with indocyanine green lymphography confirmed unilateral arm lymphedema (n = 197) and healthy controls (n = 267) were assessed using a cross-sectional study design. BIS and volumetric measures were obtained in a single session. Results: The BIS lymphedema index (L-Dex) method had a significantly higher sensitivity than the excess volume approach (area under the curve = 0.832 vs. 0.649, p = 0.0001). A threshold of L-Dex 6.5 had a higher true positive rate (70.6%) than L-Dex 10 (68.5%) although false positive rate increased from 0.4% to 2.6%. A threshold of 5% excess volume improved the true positive rate (68.5%) compared with 10% excess volume (49.7%) however the false positive rate increased to an unacceptable 47%. The L-Dex ranges in this study were not significantly different from previously published ranges. Conclusion: BIS was superior for identifying BCRL compared with volume measurements, reaffirming the value of this technique. However, it is recommended that BIS be used in conjunction with comprehensive evaluation of symptoms and clinical presentation. The proposed graphical method provides a simple and easily interpretable approach to compare and define concordance between the two commonly used methods for BCRL assessment namely limb volume and BIS L-Dex indices. The existing BIS (L-Dex) thresholds for presence of BCRL were also validated.

Effects of Body Positioning When Assessing Lymphedema of the Lower Limb Using Bioimpedance Spectroscopy.

Background: Bioimpedance spectroscopy (BIS) measurements are conventionally performed in supine position with a lead device attached to gel-backed electrodes, and more recently, with a stand-on device that uses fixed stainless-steel electrodes under the hands and feet. The aim of this study was to assess and compare BIS measurements made in supine, sitting, and standing positions using lead and stand-on impedance devices in participants with and without unilateral leg lymphedema. Materials and Methods: Participants with self-ascribed unilateral leg lymphedema (n = 24) and healthy controls (n = 71) were recruited using a cross-sectional study design. Triplicate BIS measurements were taken for each device in each position. Results: Impedance measurements with either device were reliable with coefficient of variation of 0.6% or lower. The magnitude of mean differences in absolute impedance values between devices were between 1% and 6% dependent on condition. L-Dex scores between the two devices were highly correlated (r = 0.82) and ∼70% of participants in the lymphedema group were classified as having lymphedema using the recommended cut-off with either device. There was no significant interleg difference of controls using the lead device; however, small, but significant differences (p = 0.0001) were found when using the stand-on device. Conclusion: The findings demonstrate that reliable impedance measurements of the legs can be made with either device in lying, sitting, or standing positions. However, data between the devices were not directly interchangeable. Although the risk of misidentification was small, reference ranges appropriate to the device and measurement position should be used when converting data to L-Dex scores.

Bioimpedance spectroscopy for breast cancer-related lymphedema assessment: clinical practice guidelines.

PURPOSE: Breast cancer-related lymphedema (BCRL) represents a significant concern for patients following breast cancer treatment, and assessment for BCRL represents a key component of survivorship efforts. Growing data has demonstrated the benefits of early detection and treatment of BCRL. Traditional diagnostic modalities are less able to detect reversible subclinical BCRL while newer techniques such as bioimpedance spectroscopy (BIS) have shown the ability to detect subclinical BCRL, allowing for early intervention and low rates of chronic BCRL with level I evidence. We present updated clinical practice guidelines for BIS utilization to assess for BCRL. METHODS AND RESULTS: Review of the literature identified a randomized controlled trial and other published data which form the basis for the recommendations made. The final results of the PREVENT trial, with 3-year follow-up, demonstrated an absolute reduction of 11.3% and relative reduction of 59% in chronic BCRL (through utilization of compression garment therapy) with BIS as compared to tape measurement. This is in keeping with real-world data demonstrating the effectiveness of BIS in a prospective surveillance model. For optimal outcomes patients should receive an initial pre-treatment measurement and subsequently be followed at a minimum quarterly for first 3 years then biannually for years 4-5, then annually as appropriate, consistent with previous guidelines; the target for intervention has been changed from a change in L-Dex of 10 to 6.5. The lack of pre-operative measure does not preclude inclusion in the prospective surveillance model of care. CONCLUSION: The updated clinical practice guidelines present a standardized approach for a prospective model of care using BIS for BCRL assessment and supported by evidence from a randomized controlled trial as well as real-world data.

Measurement Properties of the Lymphedema Life Impact Scale.

Background: The updated Lymphedema Life Impact Scale (LLIS, version 2) has been widely used to evaluate the effect of lymphedema from the patient's perspective. We sought to assess its ability to accurately and efficiently measure lymphedema-related impact using modern psychometric techniques. Methods and Results: We collected a total of 1054 patient-reported outcome measure scores from 285 patients with upper extremity lymphedema and 65 patients with lower extremity lymphedema between 2016 and 2020. We first evaluated the relationship between the LLIS score, L-Dex score, and limb volume difference (LVD), and used classical test and item response theories to assess its psychometric performance. The LLIS score was only very weakly associated with LVD (r = 0.17, p < 0.001) and L-Dex score (r = 0.22, p < 0.001). The LLIS had acceptable dimensionality. Items 7 (affects body image) and 16 (affects proper fit of clothing/shoes) were locally dependent (Yen's Q3 = 0.45). Eight of the 17 items was interpreted differently between upper and lower limb lymphedema patients (pseudo R2 ≥ 0.01). The scoring structure required correction for items 9 (affects intimate relations) and 12 (manages lymphedema). Removing items 18 (infection occurrence) and 7 resulted in substantially improved item response theory model fit (Tucker-Lewis index = 0.93, comparative fix index = 0.95, root mean square error of approximation = 0.07, and root means square of the residual = 0.06). The relationships between the LLIS and objective measures of lymphedema remained weak following modification (LVD; r = 0.13, p = 0.01, L-Dex; r = 0.26, p < 0.001). Conclusion: We were able to slightly improve the psychometric properties of the LLIS. However, these improvements did not rectify apparent issues with construct validity and both versions of the LLIS displayed a weak relationship with objective measures of lymphedema severity.

Body Positional Effects on Bioimpedance Spectroscopy Measurements for Lymphedema Assessment of the Arm.

Background: Bioimpedance spectroscopy (BIS) measurements have conventionally been performed using a device that uses gel-backed electrodes with the patient in a supine position. More recently, impedance devices that use stainless steel electrodes with the patient in a standing position have become available. The aim of this study was to assess and compare BIS measurements made in three different body positions using two different impedance devices (lead device and stand-on device) in women with and without arm lymphedema. Methods: A cross-sectional study design was used to recruit two cohorts of women, healthy controls (n = 47) and those who had been diagnosed with breast cancer (n = 53) and were either at risk of (n = 14) or with unilateral arm lymphedema (n = 39). BIS measurements were taken three times in each position for each device. Results: Impedance measurements were reliably made using either a lead or stand-on device with a coefficient of variation being 0.6% or lower. Absolute impedance measurements for the stand-on device were larger than the comparable lead device values due to the difference in electrode position, but were highly correlated (r = 0.92, p < 0.0001). Interarm impedance ratios and L-Dex scores were slightly (3.1% equivalence), but significantly different. Conclusion: The findings support impedance measurements being made reliably using either the lead or stand-on device, representing supine and upright measurement positions, respectively. Data between devices were, however, not directly interchangeable.

Preoperative Assessment of Upper Extremity Secondary Lymphedema.

Introduction: The purpose of this study was to evaluate the most commonly used preoperative assessment tools for patients undergoing surgical treatment for secondary upper extremity lymphedema. Methods: This was a prospective cohort study performed at a tertiary cancer center specializing in the treatment of secondary lymphedema. Lymphedema evaluation included limb volume measurements, bio-impedance, indocyanine green lymphography, lymphoscintigraphy, magnetic resonance angiography, lymphedema life impact scale (LLIS) and upper limb lymphedema 27 (ULL-27) questionnaires. Results: 118 patients were evaluated. Limb circumference underestimated lymphedema compared to limb volume. Bioimpedance (L-Dex) scores highly correlated with limb volume excess (r2 = 0.714, p < 0.001). L-Dex scores were highly sensitive and had a high positive predictive value for diagnosing lymphedema in patients with a volume excess of 10% or more. ICG was highly sensitive in identifying lymphedema. Lymphoscintigraphy had an overall low sensitivity and specificity for the diagnosis of lymphedema. MRA was highly sensitive in diagnosing lymphedema and adipose hypertrophy as well as useful in identifying axillary vein obstruction and occult metastasis. Patients with minimal limb volume difference still demonstrated significantly impaired quality of life. Conclusion: Preoperative assessment of lymphedema is complex and requires multimodal assessment. MRA, L-Dex, ICG, and PROMs are all valuable components of preoperative assessment.

Implementation of Single-Tab Electrodes for Bioimpedance Spectroscopy Measures.

Background: Bioimpedance spectroscopy (BIS) demonstrates proficiency in early identification of breast cancer treatment-related lymphedema (BCRL) development. Dual-tab electrodes were designed for consistent and easy electrode placement, however, single-tab electrodes positioned to mimic dual-tab placement on the body may make BIS technology more accessible in community hospitals and outpatient settings. The purpose of this study is to evaluate use of single-tab electrodes for BIS measurements and assess whether single-tab electrodes provide consistent BIS measurements in controls and patients with BCRL. Methods and Results: Upper limb BIS ratios were obtained using ImpediMed L-Dex® U400 in controls (n = 13; age = 23-75 years; 9 repeated measurements) using dual-tab and single-tab electrodes. BCRL patients (n = 17; Stage = 1.65 ± 0.49; number nodes removed = 16.3 ± 7.7; age = 50.9 ± 10.6 years; age range = 33-77 years) and healthy controls (n = 19) were evaluated to determine if single-tab electrodes provided discriminatory capacity for detecting BCRL. Intraclass correlation coefficients (ICC), linear mixed-effects models, Wilcoxon rank-sum tests, and linear regression with two-sided p-values <0.05 required for significance were applied. Single-tab electrodes were found to be statistically interchangeable with dual-tab electrodes (ICC = 0.966; 95% confidence interval = 0.937-0.982). No evidence of differences in single-tab versus dual-tab measurements were found for L-Dex ratios (p = 0.74) from the linear mixed-effects model. Repeated trials involving reuse of the same electrodes revealed a trend toward increases in L-Dex ratio for both styles of electrodes. Single-tab electrodes were significant (p < 0.0001) for discriminating between BCRL and control subjects. Conclusion: Findings expand upon the potential use of BIS in clinic and research settings and suggest that readily available single-tab electrodes provide similar results as dual-tab electrodes for BIS measurements.

Variation in Measurement Results Using Bioimpedance Spectroscopy to Determine Extracellular Fluid of Upper Extremity.

Background: The L-Dex U400 is a recently developed measurement device to aid in the clinical assessment of unilateral lymphedema. Until now, little is known about variation in measurement results of the L-Dex U400. The aim of this study was to determine variation in measurement results in determining extracellular fluid of the arm with the L-Dex U400 under different measurement conditions on 2 days and to determine the reliability of these measurements in healthy subjects. Methods and Results: Thirty participants were included. Participants were measured on 2 days, 2 weeks apart. Each day they were measured six times, 1st basic measurement, 2nd after a 10-minute rest period, 3rd second observer, 4th after drinking 200 mL of coffee and rest for 30 minutes on the examination couch, 5th after 30 minutes of cycling on an exercise bike at 50 W and 50-60 rounds per minute, and 6th after a 10-minute rest period. The variance due to participants was 68% of the total variance and 32% was error variance. Lin's concordance coefficient (CCC), a reliability measure, ranged from 0.935 (first day, 1st and 2nd measurement of observer 1) to 0.517 (first and second day after a 10-minute rest period after cycling). In two CCCs, the lower limits of the 95% confidence interval were higher than 0.750. Repeatability coefficient was smallest for the basic observations on day 2 (4.6) and largest after cycling (8.0). Conclusions: Clinical decision-making based on L-Dex U400 measurements should be regarded with caution because of moderate reliability.

Multi-segment bioimpedance can assess patients with bilateral lymphedema.

BACKGROUND: Bioimpedance spectroscopy (BIS) is used to assess lymphedema by measuring limb fluid content as an electric current passes through cell membranes and tissues. There are two primary device modalities, through which BIS is used clinically: single-segment bioimpedance (SSB) and multi-segment bioimpedance (MSB), which differ in their mechanisms of gathering measurements. In this cross-sectional study, we study the difference between SSB and MSB in evaluating lymphedema by referencing the results with indocyanine Green (ICG) lymphography. METHODS: Patients with unilateral and bilateral lymphedema, presented to our department, were assessed with both SSB and MSB as part of a pre-lymphatic surgery evaluation between May 1, 2017, and November 31, 2017. Patients were imaged with ICG lymphography to confirm lymphedema presence. Standardized device measurement outputs from SSB and MSB were recorded and statistically analyzed. RESULTS: SSB was more sensitive (0.9) than MSB (0.75) for unilateral lymphedema. However, MSB had the added ability to assess patients with bilateral lymphedema with a sensitivity of 0.56 and specificity of 0.60. Furthermore, MSB had a stronger correlation with relative disease severity compared to SSB and quantified the differential extents of edema. In comparison, SSB provided a manipulated number, which was derived from a comparison of the abnormal to the normal limb. Medical staff reported MSB being easier to perform, and all patients reported the MSB measurement experience being more favorable. CONCLUSIONS: While both SSB and MSB provide diagnostic information on lymphedema, MSB is notably easier to perform, can detect bilateral disease states, and objectively quantifies limb fluid volume, allowing for disease tracking and assessment of surgical and rehabilitative treatment efficacy. On the basis of this study, our department has switched to universal MSB measurement.

Bioimpedance spectroscopy is not associated with a clinical diagnosis of breast cancer-related lymphedema.

The objective of this study was to evaluate the accuracy of bioimpedance spectroscopy measurements (L-Dex) in the diagnosis of breast cancer-related lymphedema. A retrospective review of a prospectively maintained database was performed of all patients that underwent surgical treatment for breast cancer at a tertiary medical center. Patients who had preoperative and postoperative evaluation for possible lymphedema by limb circumference measurements and bioimpedance were eligible for inclusion in the study. No significant demographic differences were found between the group of patients clinically diagnosed with lymphedema (N=134) and those without a clinical diagnosis of lymphedema (N=261). The ability of bioimpedance to diagnose lymphedema based on the manufacturer's criteria demonstrated low sensitivity, which was 7.5% when lymphedema was defined as an absolute L-Dex value greater than 10, and 24.6% when defined as a relative change of >10 between preoperative and postoperative measurements. This corresponded with a positive predictive value of 61-71% and a negative predictive value of 67-70%. We are unable to recommend the use of bioimpedance as a screening tool or for measurement of breast cancer-related lymphedema.

Diagnostic accuracy of bioimpedance spectroscopy in patients with lymphedema: A retrospective cohort analysis.

BACKGROUND: Bioimpedance spectroscopy (BIS) is used by healthcare specialists to diagnose lymphedema. BIS measures limb fluid content by assessing tissue resistance to the flow of electric current. However, there is debate regarding the validity of BIS in diagnosing early lymphedema. Indocyanine green (ICG) lymphography has been established as the most accurate diagnostic modality to date for lymphedema diagnosis. In this retrospective study, we test the sensitivity, specificity, and diagnostic accuracy of BIS in diagnosing lymphedema by referencing its results with ICG lymphography. METHODS: Patients presented to the University of Iowa Lymphedema Center from 2015 to 2017 were evaluated with a standardized protocol that included history and physical examination, a validated lymphedema-specific quality-of-life assessment (LYMQOL), circumference -measurement-based index, BIS, and ICG lymphography. Diagnostic accuracy of BIS was assessed using ICG lymphography as a reference test. RESULTS: Fifty-eight patients had positive ICG lymphography results, which confirmed the diagnosis of lymphedema. ICG lymphographic findings consistently correlated with clinical examination, LYMQOL evaluation, and lymphedema indices. By contrast, BIS demonstrated a false-negative rate of 36% - 21 out of 58 patients had normal BIS readings, but a positive ICG lymphography result. The 21 false-negative results occurred in patients with early-stage disease. Sensitivity and specificity for BIS were 0.64 and 1, respectively. CONCLUSION: BIS carries an excessively high rate of false-negative results to be dependably used as a diagnostic modality for lymphedema. ICG lymphography highly correlates with other tracking modalities, and it remains the most reliable tool for diagnosing lymphedema.

Utilization of bioimpedance spectroscopy in the prevention of chronic breast cancer-related lymphedema.

BACKGROUND: This analysis was performed to assess the impact of early intervention following prospective surveillance using bioimpedance spectroscopy (BIS) to detect and manage breast cancer-related lymphedema (BCRL). METHODS: From 8/2010 to 12/2016, 206 consecutive patients were evaluated with BIS. The protocol included pre-operative assessment with L-Dex as well as post-operative assessments at regular intervals. Patients with L-Dex scores >10 from baseline were considered to have subclinical BCRL and were treated with over-the-counter (OTC) compression sleeve for 4 weeks. High-risk patients were defined as undergoing axillary lymph node dissection (ALND), receiving regional nodal irradiation (RNI), or taxane chemotherapy. Chronic BCRL was defined as the need for complex decongestive physiotherapy (CDP). RESULTS: Median follow-up was 25.9 months. Overall, 17% of patients had one high-risk feature, 8% two, and 7% had three. 9.8% of patients were diagnosed with subclinical BCRL with highest rates seen following ALND (23 vs. 7%, p = 0.01). Development of subclinical BCRL was associated with ALND and receipt of RNI. At last follow-up, no patients (0%) developed chronic, clinically detectable, BCRL. Subset analysis was performed of the 30 patients undergoing ALND. Median number of nodes removed was 18 and median number of positive nodes was 2. 77% received taxane chemotherapy, 62% axillary RT, and 48% had elevated BMI. Overall, 86% of patients had at least one additional high-risk feature, 70% at least two, and 23% had all three. Seven patients (23%) had abnormally elevated L-Dex scores at some point during follow-up. To date, none has required CDP. CONCLUSIONS: The results of this study support prospective surveillance utilizing BIS initiated pre-operatively with subsequent post-operative follow-up measurements for the detection of subclinical BCRL. Intervention triggered by subclinical BCRL detection with an elevated L-Dex score was associated with no cases progressing to chronic, clinically detectable BCRL even in very high-risk patients.

The Impact of L-Dex(®) Measurements in Assessing Breast Cancer-Related Lymphedema as Part of Routine Clinical Practice.

PURPOSE: With improved survivorship, the prevalence of breast cancer-related lymphedema (BCRL) continues to increase, leading to impairment of a patients' quality of life. While traditional diagnostic methods are limited by an inability to detect BCRL until clinically apparent, bioimpedance spectroscopy (BIS) has been shown to detect subclinical BCRL. The purpose of this study is to evaluate the role of BIS in the early detection of BCRL, as well as assessment of response to BCRL treatment. METHODS: A retrospective review of 1,133 patients treated between November 2008 and July 2013 at two surgical practices was performed. Eligible patients (n = 326) underwent preoperative and postoperative L-Dex measurements. Patients were identified as having subclinical lymphedema if they were asymptomatic and the L-Dex score increased >10 U above baseline and were monitored following treatment. Patients were stratified by lymph node dissection technique [sentinel lymph node biopsy (SLNB) vs. axillary lymph node dissection (ALND)] and receipt of BCRL treatment. RESULTS: The average age of the cohort was 56.2 years old, and mean follow-up was 21.7 months. Of the 326 patients, 210 underwent SLNB and 116 underwent ALND. BCRL was identified by L-Dex in 40 patients (12.3%). The cumulative incidence rate of subclinical lymphedema was 4.3% for SLNB (n = 9) and 26.7% for ALND (n = 31). Of those diagnosed with BCRL, 50% resolved following treatment, 27.5% underwent treatment without resolution, and 22.5% had resolution without treatment. The prevalence of persistent, clinical BCRL was 0.5% for SLNB and 8.6% for ALND. CONCLUSION: This study demonstrates both the feasibility and clinical utility of implementing L-Dex measurements in routine breast cancer care. L-Dex identified patients with possible subclinical BCRL and allowed for assessment of response to therapy.

A comprehensive review of bioimpedance spectroscopy as a diagnostic tool for the detection and measurement of breast cancer-related lymphedema.

As treatment for breast cancer improves and the threat of life-long chronic lymphedema becomes more prevalent, the need for effective screening tools emerges as crucial. This review was conducted using literature beginning in 1992 to analyze primary research testing the accuracy of bioimpedance spectroscopy as a diagnostic and early detection tool for breast cancer-related lymphedema. We concluded bioimpedance is an accurate diagnostic tool for pre-existent lymphedema, however, it has not been validated for early detection. J. Surg. Oncol. 2016;114:537-542. © 2016 Wiley Periodicals, Inc.