Clinical trial NCT03210311: Pre-existing Factors, Early Detection and Early Treatment of Breast Cancer Related Lymphedema
Official title: Determining the Role of Pre-existing Factors, Early Diagnostic Options and Early Treatment in the Development of Breast Cancer Related Lymphedema
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Lymphedema of Upper Arm
Breast Cancer
Diagnoses Disease
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
First posted: 2017-07-06
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of lymphedema of arm and hand
timeFrame: up to 36 months
measure: Deterioration of dermal backflow
timeFrame: up to 36 months
Secondary outcomes:
measure: Change of extracellular fluid change of extracellular fluid
timeFrame: up to 36 months
measure: Change of quality of life
timeFrame: up to 36 months
measure: change of pitting status
timeFrame: up to 36 months
measure: Change of water content
timeFrame: up to 36 months
measure: change of skinfold tickness
timeFrame: up to 36 months
measure: relative change of arm volume difference
timeFrame: up to 36 months
measure: severity of disturbance of lymphatic transport
timeFrame: up to 36 months
measure: problems in functioning related to development of lymphedema
timeFrame: up to 36 months
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: Vascular surgey Lymphovenous center
state: Vlaams Brabant
Study officials:
affiliation: UZ Leuven
name: Sarah Thomis, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.