Development of a Clinical Screening, Diagnostic and Evaluation Tool for Patients With Lower Limb Lymphedema: Aim 2 (EvaLymph-Leg2)

Development of a Clinical Screening, Diagnostic and Evaluation Tool for Patients With Lower Limb Lymphedema: Development of a Screening Set for Patients at Risk for Developing LLL

Lymphedema is a chronic, debilitating disorder characterized by abnormal tissue swelling, adipose deposition and tissue fibrosis, resulting from disruption, blockage, or genetic abnormalities of the lymphatic system. Secondary lymphedema is an acquired lymphedema due to trauma, surgery, radiotherapy or infection among others resulting in a decreased transport capacity of the lymphatic system. This can be combined with an additional load on the lymphatic system due to obesity, venous hypertension or a wound, among others. Advances in oncologic treatment have led to an ever-increasing number of cancer survivors over time. As a result, morbidities related to this treatment (such as secondary lymphedema) are likely to increase too.

Risk factors for the development of LLL after treatment for (gynaecological) cancer are: pelvic and para-aortic lymphadenectomy, the number of pelvic lymph nodes removed, adjuvant radiotherapy, adjuvant chemotherapy, increasing BMI/ BMI ≥25 kg/m², lymphocyst formation, increasing age, increasing time since surgery and insufficient physical activity level.

To the investigators knowledge, no evidence exists regarding which (combination of) measuring methods are most sensitive to detect early lymphedema at the lower limbs after the treatment of cancer. Thresholds for identifying subclinical edema on one or both lower limbs are lacking.

Therefore the investigators want to develop a screening set for patients at risk for developing LLL. Which measurement method (and which criterion) shows the best diagnostic accuracy in screening patients at risk for LLL after cancer treatment? And: What is the added value of combining different measurement methods in terms of diagnostic accuracy?

Study Overview

• Status: Recruiting
• Conditions: Lower Limb Lymphedema
• Intervention / Treatment: Diagnostic test: clinical assessment

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

• Study Contact: Name: Tessa De Vrieze, Dr.; Phone Number: 003216345006; Email: tessa.devrieze@kuleuven.be

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Recruiting
    • University Hospitals of Leuven
    • Contact: Tessa De Vrieze, Dr.; Phone Number: 003216345006; Email: tessa.devrieze@kuleuven.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

patients at risk for LLL (i.e. patients undergoing pelvic/inguinal/para-aortic lymph node dissection for uro-genital, gynaecological or skin cancer) will be included from pre-surgery up to 12 months post-surgery

Description

Inclusion Criteria:

• Patients with a diagnosis of skin melanoma (at the level of the lower limb, at least cancer stage 3), gynecological cancer, uro-genital cancer that will receive surgery (sentinel lymph node biopsy and/or (para-aortic/inguinal/pelvic) lymph node dissection)

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
lymph node dissection for treatment of urogenital, gynaelogical or skin cancer; Patients with any type of skin melanoma (at the level of the lower limb), urogenital or gynaecological cancer scheduled for lymph node dissection	Diagnostic test: clinical assessment; screening of patients at risk for developing unilateral or bilateral lower limb lymphedema

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity of reliable and clinical feasible measurement methods regarding the screening of patients at risk for developing unilateral or bilateral LLL	Sensitivity of reliable and clinical feasible measurement methods (resulted from aim 1: NCT05269264) regarding the screening of patients at risk for developing unilateral or bilateral LLL at 6 weeks, 6, and 12 months post-surgery	up to 12 months post-surgery
Specificity of reliable and clinical feasible measurement methods regarding the screening of patients at risk for developing unilateral or bilateral LLL	Specificity of reliable and clinical feasible measurement methods (resulted from aim 1: NCT05269264) regarding the screening of patients at risk for developing unilateral or bilateral LLL at 6 weeks, 6, and 12 months post-surgery	up to 12 months post-surgery
Diagnostic accuracy of reliable and clinical feasible measurement methods regarding the screening of patients at risk for developing unilateral or bilateral LLL	Diagnostic accuracy of reliable and clinical feasible measurement methods (resulted from aim 1: NCT05269264) regarding the screening of patients at risk for developing unilateral or bilateral LLL at 6 weeks, 6, and 12 months post-surgery	up to 12 months post-surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prognostic value of 'baseline age' for the development of bilateral lower limb lymphoedema at 6 weeks post-surgery	Dependent variable = presence of lower limb lymphoedema Independent variable= Age (years) will be self-reported through interview.	6 weeks post-surgery
Prognostic value of 'baseline age' for the development of bilateral lower limb lymphoedema at 12 months post-surgery.	Dependent variable = presence of lower limb lymphoedema Independent variable= Age (years) will be self-reported through interview.	12 months post-surgery
Prognostic value of ' Baseline physical activity level' for the development of bilateral lower limb lymphoedema at 6 weeks post-surgery	Dependent variable = presence of lower limb lymphoedema Independent variable= Baseline physical activity level : will be assessed with the International Physical Activity Questionnaire (IPAQ). The IPAQ is a 27-item self-reported measure of physical activity for use with individual adult patients aged 15 to 69 years old. Results can be reported in categories (low activity levels, moderate activity levels or high activity levels) or as a continuous variable (MET minutes a week). MET minutes represent the amount of energy expended carrying out physical activity.	6 weeks post-surgery
Prognostic value of ' Baseline physical activity level' for the development of bilateral lower limb lymphoedema at 12 months post-surgery	Dependent variable = presence of lower limb lymphoedema Independent variable= Baseline physical activity level : will be assessed with the International Physical Activity Questionnaire (IPAQ). The IPAQ is a 27-item self-reported measure of physical activity for use with individual adult patients aged 15 to 69 years old. Results can be reported in categories (low activity levels, moderate activity levels or high activity levels) or as a continuous variable (MET minutes a week). MET minutes represent the amount of energy expended carrying out physical activity.	12 months post-surgery
Prognostic value of ' Baseline educational level' for the development of bilateral lower limb lymphoedema at 6 weeks post-surgery	Dependent variable = presence of lower limb lymphoedema Independent variable= Educational level: will be self-reported through interview.	6 weeks post-surgery
Prognostic value of ' Baseline educational level' for the development of bilateral lower limb lymphoedema at 12 months post-surgery	Dependent variable = presence of lower limb lymphoedema Independent variable= Educational level: will be self-reported through interview.	12 months post-surgery
Prognostic value of ' Baseline BMI' for the development of bilateral lower limb lymphoedema at 6 weeks post- surgery	Dependent variable = presence of lower limb lymphoedema Independent variable= baseline Body Mass Index	6 weeks post- surgery
Prognostic value of ' Baseline BMI' for the development of bilateral lower limb lymphoedema at 12 months post- surgery	Dependent variable = presence of lower limb lymphoedema Independent variable= baseline Body Mass Index	12 months post- surgery
Prognostic value of ' Baseline comorbidities' for the development of bilateral lower limb lymphoedema at 6 weeks post-surgery	Dependent variable = presence of lower limb lymphoedema Independent variable= baseline comorbidities Comorbidities will be reported through a self-developed co-morbidity questionnaire, based on IDEWE questionnaire.	6 weeks post-surgery
Prognostic value of ' Baseline comorbidities' for the development of bilateral lower limb lymphoedema at 12 months post-surgery	Dependent variable = presence of lower limb lymphoedema Independent variable= baseline comorbidities Comorbidities will be reported through a self-developed co-morbidity questionnaire, based on IDEWE questionnaire.	12 months post-surgery
Prognostic value of 'Type of cancer' for the development of bilateral lower limb lymphoedema at 6 weeks post-surgery	Dependent variable = presence of lower limb lymphoedema Independent variable= Type of cancer Information regarding the type of cancer is collected by exploring the patient's medical file.	6 weeks post-surgery
Prognostic value of 'Type of cancer' for the development of bilateral lower limb lymphoedema at 12 months post-surgery	Dependent variable = presence of lower limb lymphoedema Independent variable= Type of cancer Information regarding the type of cancer is collected by exploring the patient's medical file.	12 months post-surgery
Prognostic value of 'Tumor stage' for the development of bilateral lower limb lymphoedema at 6 weeks post-surgery	Dependent variable = presence of lower limb lymphoedema Independent variable= Tumor stage Information regarding the tumor stage of is collected by exploring the patient's medical file.	at 6 weeks post-surgery
Prognostic value of 'Tumor stage' for the development of bilateral lower limb lymphoedema at 12 months post-surgery	Dependent variable = presence of lower limb lymphoedema Independent variable= Tumor stage Information regarding the tumor stage of is collected by exploring the patient's medical file.	12 months post-surgery
Prognostic value of 'Lymph node stage' for the development of bilateral lower limb lymphoedema at 6 weeks post-surgery	Dependent variable = presence of lower limb lymphoedema Independent variable= Lymph node stage Information regarding the lymph node stage of is collected by exploring the patient's medical file.	6 weeks post-surgery
Prognostic value of 'Lymph node stage' for the development of bilateral lower limb lymphoedema at 12 months post-surgery	Dependent variable = presence of lower limb lymphoedema Independent variable= Lymph node stage Information regarding the lymph node stage of is collected by exploring the patient's medical file.	12 months post-surgery
Prognostic value of 'Number of positive lymph nodes' for the development of bilateral lower limb lymphoedema at 6 weeks post-surgery	Dependent variable = presence of lower limb lymphoedema Independent variable=Number of positive lymph nodes: is collected through the patient's medical file.	6 weeks post-surgery
Prognostic value of 'Number of positive lymph nodes' for the development of bilateral lower limb lymphoedema at 12 months post-surgery	Dependent variable = presence of lower limb lymphoedema Independent variable=Number of positive lymph nodes: is collected through the patient's medical file.	12 months post-surgery
Prognostic value of 'Postoperative complications' for the development of bilateral lower limb lymphoedema at 6 weeks post-surgery	Information regarding the complications related to the surgery as well as adjuvant therapies is collected. Surgical complications will be assessed according to the Clavien-Dindo Classification of Surgical Complications.	6 weeks post-surgery
Prognostic value of 'Postoperative complications' for the development of lower limb lymphoedema at 12 months post-surgery	Information regarding the complications related to the surgery as well as adjuvant therapies is collected. Surgical complications will be assessed according to the Clavien-Dindo Classification of Surgical Complications.	12 months post-surgery
Prognostic value of 'Type of lymph node dissection' for the development of bilateral lower limb lymphoedema at 6 weeks post-surgery	Cancer treatment characteristics are collected (i.e. type of surgery, type of lymph node dissection, number of lymph nodes removed, presence of postoperative drain, number of positive lymph nodes, adjuvant therapies; by exploring the patient's medical file. Type of lymph node dissection: Limited- Standard- Extended- Super extended	6 weeks post-surgery
Prognostic value of 'Type of lymph node dissection' for the development of bilateral lower limb lymphoedema at 12 months post-surgery	Cancer treatment characteristics are collected (i.e. type of surgery, type of lymph node dissection, number of lymph nodes removed, presence of postoperative drain, number of positive lymph nodes, adjuvant therapies; by exploring the patient's medical file. Type of lymph node dissection: Limited- Standard- Extended- Super extended	12 months post-surgery
Prognostic value of 'Number of lymph nodes removed' for the development of bilateral lower limb lymphoedema at 6 weeks post-surgery	Cancer treatment characteristics are collected (i.e. type of surgery, type of lymph node dissection, number of lymph nodes removed, presence of postoperative drain, number of positive lymph nodes, adjuvant therapies; by exploring the patient's medical file.	6 weeks post-surgery
Prognostic value of 'Number of lymph nodes removed' for the development of bilateral lower limb lymphoedema at 12 months post-surgery	Cancer treatment characteristics are collected (i.e. type of surgery, type of lymph node dissection, number of lymph nodes removed, presence of postoperative drain, number of positive lymph nodes, adjuvant therapies; by exploring the patient's medical file.	12 months post-surgery
Prognostic value of 'Adjuvant Radiotherapy' for the development of bilateral lower limb lymphoedema at 6 weeks post-surgery	Cancer treatment characteristics , including adjuvant radiotherapy are collected; by exploring the patient's medical file.	6 weeks post-surgery
Prognostic value of 'Adjuvant Radiotherapy' for the development of bilateral lower limb lymphoedema at 12 months post-surgery	Cancer treatment characteristics , including adjuvant radiotherapy are collected; by exploring the patient's medical file.	12 months post-surgery
Incidence rate of unilateral and bilateral LLL at 6 weeks post-surgery	Calculation of the proportion of patients with leg (or foot) lymphedema, defined as 5.0% or more increase of the leg (or foot) volume in each leg (or foot), at a certain time point, compared to the volumes at baseline; OR patients with a score of at least 5 out of 52 on the detect-OL questionnaire in case it is clearly indicated whether symptoms are present in one or both legs (in order to be able to categorize patients to the "unilateral LLL" or "bilateral LLL" group). Additionally, the proportion of presence of LLL in patients having received a lymph node dissection due to gynaecological cancer vs. due to urogenital cancer vs. due to skin melanoma will be compared. The distribution of LLL (unilateral vs. bilateral, regions of the lower limb) will be encountered and compared.	6 weeks post-surgery
Incidence rate of unilateral and bilateral LLL at 6 months post-surgery	Calculation of the proportion of patients with leg (or foot) lymphedema, defined as 5.0% or more increase of the leg (or foot) volume in each leg (or foot), at a certain time point, compared to the volumes at baseline; OR patients with a score of at least 5 out of 52 on the detect-OL questionnaire in case it is clearly indicated whether symptoms are present in one or both legs (in order to be able to categorize patients to the "unilateral LLL" or "bilateral LLL" group). Additionally, the proportion of presence of LLL in patients having received a lymph node dissection due to gynaecological cancer vs. due to urogenital cancer vs. due to skin melanoma will be compared. The distribution of LLL (unilateral vs. bilateral, regions of the lower limb) will be encountered and compared.	6 months post-surgery
Incidence rate of unilateral and bilateral LLL at 12 months post-surgery	Calculation of the proportion of patients with leg (or foot) lymphedema, defined as 5.0% or more increase of the leg (or foot) volume in each leg (or foot), at a certain time point, compared to the volumes at baseline; OR patients with a score of at least 5 out of 52 on the detect-OL questionnaire in case it is clearly indicated whether symptoms are present in one or both legs (in order to be able to categorize patients to the "unilateral LLL" or "bilateral LLL" group). Additionally, the proportion of presence of LLL in patients having received a lymph node dissection due to gynaecological cancer vs. due to urogenital cancer vs. due to skin melanoma will be compared. The distribution of LLL (unilateral vs. bilateral, regions of the lower limb) will be encountered and compared.	12 months post-surgery

Collaborators and Investigators

• Sponsor: KU Leuven
• Collaborators: Universitaire Ziekenhuizen KU Leuven
• Investigators: Principal Investigator: Tessa De Vrieze, Dr., KU Leuven

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2022
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: June 13, 2022
• First Submitted That Met QC Criteria: June 13, 2022
• First Posted (Actual): June 16, 2022

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: screening; lymph node dissection; urogenital cancer; skin cancer; gynaecological cancer
• Additional Relevant MeSH Terms: Lymphatic Diseases; Lymphedema
• Other Study ID Numbers: s66033-aim2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No