Development of a Clinical Screening, Diagnostic and Evaluation Tool for Patients With Lower Limb Lymphedema: Aim 3

Study Overview
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Brief Summary
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The current best practice is a three-stage classification consensus guideline as published by the International Society of Lymphology (ISL). Severity of lymphedema is however not only determined by presence of pitting (which is the phenomenon when the swollen area has a dimple (or pit) after you press it for 5 to 10 seconds) and presence of adipose tissue or not, but is also determined by the volume of the edema, a quantification of the condition of the skin and the location/expansion of the edema over the body. Currently a severity score considering these different aspects does not exist. Although there is consensus that the ISL staging systems is a necessary part of the diagnosis of lymphedema, it gives not enough information about the severity of the lymphedema. A more detailed and comprehensive classification system applicable for primary and secondary lymphedema and considering multiple edema characteristics, remains to be formulated. The researchers objective in this study is to develop a diagnostic set, including a 'severity score', for patients with LLL.

Official Title
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Development of a Clinical Screening, Diagnostic and Evaluation Tool for Patients With Lower Limb Lymphedema: Development of a Diagnostic Set for Patients With LLL

Conditions
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Lower Limb Lymphedema

Intervention / Treatment
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* Diagnostic Test: Lower Limb Lymhedema assessment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient group Unilateral or bilateral, primary or secondary LLL Objective diagnosis of lymphedema: ≥ 5% volume difference between both legs OR ≥ 2 minor/ 1 major criteria on lymphoscintigraphy OR presence of ICG dermal backflow Age ≥ 18 years Able to read, understand and speak Dutch Healthy controls - Age, gender & BMI-matched healthy controls Exclusion Criteria: Pregnant participants Presence of chronic venous insufficiency C4, C5, C6; deep venous thrombosis; post-thrombotic syndrome Presence of skin infections of wounds at the level of the lower limbs at the moment of inclusion

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| patients with unilateral or bilateral, primary or secundary LLL<br> | Diagnostic Test: Lower Limb Lymhedema assessment<br>* assessessment with the selected measurement methods showing sufficient reliability and feasibility in the patient group with LLL from aim 1:NCT05269264. Measurement will occur at the genital/midline region, and on both legs/ feet.<br>|
| healthy controls<br> | Diagnostic Test: Lower Limb Lymhedema assessment<br>* assessessment with the selected measurement methods showing sufficient reliability and feasibility in the patient group with LLL from aim 1:NCT05269264. Measurement will occur at the genital/midline region, and on both legs/ feet.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity of measurement methods (resulted from aim 1:NCT05269264) in diagnosing unilateral and bilateral LLL | all patients with LLL and all healthy controls will be assessed with the selected measurement methods showing sufficient reliability and feasibility in the patient group with LLL from aim 1. Measurement will occur at the genital/midline region, and on both legs/ feet. | During the recruitment period (up to 1 year), patients are scheduled for only 1 visit with duration of +/- 1 hour (cross-sectional design) | 
| Specificity of measurement methods (resulted from aim 1:NCT05269264) in diagnosing unilateral and bilateral LLL | all patients with LLL and all healthy controls will be assessed with the selected measurement methods showing sufficient reliability and feasibility in the patient group with LLL from aim 1. Measurement will occur at the genital/midline region, and on both legs/ feet. | During the recruitment period (up to 1 year), patients are scheduled for only 1 visit with duration of +/- 1 hour (cross-sectional design) | 
| Diagnostic accuracy of measurement methods (resulted from aim 1:NCT05269264) in diagnosing unilateral and bilateral LLL | all patients with LLL and all healthy controls will be assessed with the selected measurement: methods showing sufficient reliability and feasibility in the patient group with LLL from aim 1. Measurement will occur at the genital/midline region, and on both legs/ feet. To determine diagnostic accuracy of the diagnostic methods, in a first phase, data will be analysed using Receiver Operating Characteristic (ROC) curves and by calculation the area under the curve (AUC) for each individual evaluation method resulting from aim 1. Sensitivity and specificity values will be compared, and for each measurement method, the AUC (or C-statistic) will be considered. Also prognostic values and likelihood ratios will be calculated of the individual measurement methods. Lastly, to investigate discriminant validity, measurement outcomes of the patients with LLL will be correlated to the measurement outcomes of the healthy controls. | During the recruitment period (up to 1 year), patients are scheduled for only 1 visit with duration of +/- 1 hour (cross-sectional design) | 
| Development of a severity grading score for unilateral and bilateral LLL | a meeting with the international expert panel will be organized to achieve consensus regarding the measurement methods that should be performed to compile a severity score. Secondly, of all these separate measurement methods, percentiles (20, 40, 60, 80) will be calculated from the data of our study sample for this aim, serving as reference cut-off values. Consequently, 5 'severity' ranges will be presented that will correspond to a severity subscore between 0-5 for each measurement outcome. Lastly, a total severity score will be calculated | During the recruitment period (up to 1 year), patients are scheduled for only 1 visit with duration of +/- 1 hour (cross-sectional design) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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severity score, diagnostic set