Pre-existing Factors, Early Detection and Early Treatment of Breast Cancer Related Lymphedema (DEARLY)

Determining the Role of Pre-existing Factors, Early Diagnostic Options and Early Treatment in the Development of Breast Cancer Related Lymphedema

Breast-cancer related lymphoedema (BCRL) is a common phenomenon. Early diagnosis and treatment is very important to alter the normal progression of this disease. A threshold (>= 3% volume change) that recognizes subclinical lymphedema is promoted. When the lymphedema is diagnosed late, options for treatment are diminished as fibrous tissue is formed.

Preoperative investigation with near-infrared fluorescence lymphography can show an abnormality. Even if a linear transport is visualized, velocity of the transport can be diminished or a different pathway than normal can be visualized. Such an extensive evaluation has not been performed yet.

This lymphofluoroscopy gives an opportunity to detect lymphedema earlier than clinically visible (subclinical). The investigators hypothesize that the evolution of lymphedema can be altered if treatment is started in the subclinical phase.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Lymphedema of Upper Arm; Diagnoses Disease
• Intervention / Treatment: Device: compression

Detailed Description

Breast-cancer related lymphoedema (BCRL) is a common phenomenon. Estimates of incidence rates have varied over time, especially since the progression to less invasive techniques as sentinel node procedures and radiotherapy. According to a review article of DiSipio the incidence of arm lymphedema was about four times higher in women who had an axillary lymph node dissection (18 studies; 19.9%, 13.5-28.2) than in those who had sentinel lymph node biopsy (18 studies; 5.6%, 6.1-7.9). Several other risk factors are already suggested as having a negative impact on the development of lymphedema such as BMI and chemotherapy. A comprehensive overview of all treatment related risk factors and patient related risk factors, including demographics, has not been reported yet.

Lymphedema is identified with upper limb volume measurements eg circumference measurements, water displacement and perometer. Bioimpedance spectroscopy can also be used to assess the extracellular fluid. A 10% limb volume change has been reported as the most accurate threshold to diagnose lymphedema. However, with this definition an underestimation of the incidence rate of lymphoedema is made. Therefore, recently a threshold of 5% limb volume change is proposed.

A study by Rockson et al suggested that in almost 75 % of the cases, lymphoedema is established in the first year after breast cancer treatment. But up to two years after surgery, there still is a possibility to develop lymphoedema.

Early diagnosis and treatment is very important to alter the normal progression of this disease. A threshold (>= 3% volume change) that recognizes subclinical lymphedema is promoted.

When the lymphedema is diagnosed late, options for treatment are diminished as fibrous tissue is formed.

During near-infrared fluorescence lymphography (lymphofluoroscopy), a fluorescent substance is injected subcutaneously in the hand and the transport of lymph is visualized from the hand up to the axilla. A normal transport is defined as a linear image and an abnormal transport as a dermal backflow image. The dermal backflow image is divided in three different classifications according to the severity.

Preoperative investigation with near-infrared fluorescence lymphography can show an abnormality. Even if a linear transport is visualized, velocity of the transport can be diminished or a different pathway than normal can be visualized. Such an extensive evaluation has not been performed yet.

This lymphofluoroscopy gives an opportunity to detect lymphedema earlier than clinically visible (subclinical).

The investigators hypothesize that the evolution of lymphedema can be altered if treatment is started in the subclinical phase.

• Study Type: Interventional
• Enrollment (Actual): 128
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Vlaams Brabant
    • Leuven, Vlaams Brabant, Belgium, 3000
      • Vascular surgey Lymphovenous center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age >18y (since the investigation using ICG is not dangerous for pregnant women, women with child bearing age are included)
• Women/ men with breast cancer and scheduled for unilateral axillary lymph node dissection (ALND) or sentinel node biopsy (SNB)
• Oral and written approval of informed consent
• Dutch speaking

Exclusion Criteria:

• Oedema of the upper limb from other causes
• Cannot participate during the entire study period
• Mentally or physically unable to participate in the study
• Contra-indication for the use of ICG: allergy to iodine, hyperthyroidism
• Metastatic disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: control group; Receive information: the patient receive a leaflet with information about the lymphatic system and lymphedema, clinical evaluation and conservative treatment of lymphedema; Perform skin care; Perform twice a day upper limb exercises at home. They are advised to use the arm as normal as possible.
Active Comparator: intervention group; Receive information: the patient receive a leaflet with information about the lymphatic system and lymphedema, clinical evaluation and conservative treatment of lymphedema; Perform skin care; Perform upper limb exercises at home twice a day. They are advised to use the arm as normal as possible; Wear a compression sleeve	Device: compression; a compression stocking is worn, a garment compression class 2, flat knitted

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of lymphedema of arm and hand	defined as 5% volume increase compared to the contralateral side	up to 36 months
Deterioration of dermal backflow	measured by lymphofluoroscopy	up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of extracellular fluid change of extracellular fluid	measured by the BIS	up to 36 months
Change of quality of life	measured by Mc Gill questionnaire	up to 36 months
change of pitting status	measured by the pitting test at each visit	up to 36 months
Change of water content	measured with moisture meter	up to 36 months
change of skinfold tickness	measured by skinfold	up to 36 months
relative change of arm volume difference	relative volume difference at assessment - relative volume difference at baseline	up to 36 months
severity of disturbance of lymphatic transport	scoring dermal backflow in the 13 regions	up to 36 months
problems in functioning related to development of lymphedema	measured by lymph ICF questionnaire	up to 36 months

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Investigators: Principal Investigator: Sarah Thomis, MD, UZ Leuven

Publications and helpful links

General Publications

• Thomis S, Devoogdt N, Bechter-Hugl B, Nevelsteen I, Neven P, Fourneau I. Impact of a compression garment, on top of the usual care, in patients with breast cancer with early disturbance of the lymphatic transport: protocol of a randomised controlled trial. BMJ Open. 2020 Dec 4;10(12):e042018. doi: 10.1136/bmjopen-2020-042018.

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2017
• Primary Completion (Actual): April 1, 2024
• Study Completion (Actual): October 4, 2024

Study Registration Dates

• First Submitted: June 29, 2017
• First Submitted That Met QC Criteria: July 4, 2017
• First Posted (Actual): July 6, 2017

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 22, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Postoperative Complications; Pathologic Processes; Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Lymphatic Diseases; Breast Cancer Lymphedema; Breast Neoplasms; Lymphedema
• Other Study ID Numbers: S60382; 2017-002306-12 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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