Protocol of a randomised controlled trial regarding the effectiveness of fluoroscopy-guided manual lymph drainage for the treatment of breast cancer-related lymphoedema (EFforT-BCRL trial)

Tessa De Vriezea, Lore Vosa, Nick Gebruersb, Wiebren A.A. Tjalmac, Sarah Thomis, Patrick Neveng, Ines Nevelsteeng, An De Groefa, Liesbeth Vandermeerenh, Jean-Paul Belgradoh, Nele Devoogdta. European Journal of Obstetrics & Gynecology and Reproductive Biology (2017) article in press

Click to read the abstract

Protocol of a randomised controlled trial regarding the effectiveness of fluoroscopy-guided manual lymph drainage for the treatment of breast cancer-related lymphoedema (EFforT-BCRL trial)

Tessa De Vriezea, Lore Vosa, Nick Gebruersb, Wiebren A.A. Tjalmac, Sarah Thomis, Patrick Neveng, Ines Nevelsteeng, An De Groefa, Liesbeth Vandermeerenh, Jean-Paul Belgradoh, Nele Devoogdta. European Journal of Obstetrics & Gynecology and Reproductive Biology (2017) article in press

Objectives: Lymphoedema is a dreadful complication following breast cancer therapy. According to the International Society of Lymphology, the consensus treatment for breast cancer-related lymphoedema (BCRL) is the decongestive lymphatic therapy. This is a two-phase treatment and combines different treatment modalities including skin care, manual lymphatic drainage (MLD), compression therapy and exercise. However, the additional effect of MLD is debated since pooled data only demonstrated a limited non-significant additional value. A possible explanation is that in previous studies MLD has been applied blind, without knowledge of patient-specific lymphatic routes of transport. In addition, the MLD hand manoeuvres used by the therapists in previous studies, possibly did not optimally stimulate lymphatic transport. Recently, near-infrared fluorescence imaging has been introduced to visualise the superficial lymphatic network which allows MLD at the most needed location. The aim of the present study is to determine the effectiveness of the fluoroscopy-guided MLD, additional to the other parts of the decongestive lymphatic therapy and compared to the traditional or a placebo MLD, in the treatment of BCRL.

Study design: A three-arm double-blinded randomised controlled trial will be conducted in different university hospitals in Belgium. Based on a sample size calculation, 201 participants with chronic BCRL stage 1 or 2 of the arm or hand, with at least 5% difference between both sides (corrected for hand dominance) need to be recruited. All participants receive the standard treatment: skin care, compression therapy and exercises. The intervention group additionally receives fluoroscopy-guided MLD. One control group additionally receives the traditional ‘blind’ MLD and a second control group receives a placebo MLD. All subjects receive 3 weeks of daily intensive treatments and 6 months of maintenance treatment. Follow-up period is 6 months. The primary outcomes are the reduction in lymphoedema volume of the arm/hand and the change in stagnation of lymph fluid at level of the shoulder/trunk.

Main findings

  • This multicentre double blind trial 3 group RCT will have 201 participants. All participants will have:
    • Skin care, compression therapy, exercises and information.
    • 3 week intensive treatment with treatments 5 times per week.
    • 6 month maintenance treatment.
    • 6 month further follow up.
  • Group 1 fluoroscopy guided MLD, group 2 traditional MLD and group 3 placebo MLD
  • All participants are blinded for the allocation to one of the three MLD groups. All clinical as well as fluoroscopic assessments are performed by investigators who are blinded for the allocation of the patients to the treatment groups. The therapists are blinded to participants’ data, but are aware of the treatments provided to the three different groups.
  • This paper provides detailed information on the assessment of participants. The clinical assessment has primary outcomes and secondary outcomes.
  • Primary outcomes include:
    • Volume of the arm via water displacement and circumference measurements.
    • Change of stagnation of lymph at the level of the shoulder or trunk using the MoistureMeter.
  • Secondary outcomes include:
    • Extracellular fluid measurements by bio – impedance fluoroscopy.
    • Change of thickness and reflectivity of cutis and subcutis of arm/shoulder/trunk by ultrasound measurements.
    • Change of elasticity of skin and subcutaneous tissue of arm/shoulder/trunk measured with the SkinFibrometer (delfin).
    • Investigation of % of problems in functioning related to the development of arm lymphoedema using Lymph-ICF- Questionnaire with Numeric Rating Scale.
    • Investigation of Quality of Life of patients with a chronic disease using the McGill-Quality of Life Questionnaire.
    • Near-infrared fluorescence imaging or lymphofluoroscopy for investigation of superficial lymphatic system.
    • Investigation of the number of episodes of erysipelas in between two assessments.
    • Investigation of direct costs related to the treatment of (side effects of) lymphoedema.
  • This paper provides details on treatment protocols.
  • The article states “This will be the first multicentre double-blind RCT to investigate the effectiveness of lymphofluoroscopy-guided MLD, in addition to the other parts of the decongestive lymphatic therapy, for the treatment of BCRL. If the current trial is able to demonstrate a significant improvement in change of lymphoedema volume at the level of the arm/hand or in stagnation of lymph at the level of the shoulder/trunk, due to the application of fluoroscopy-guided MLD, a clear answer to the question ‘do we need to implement fluoroscopy-guided MLD in the conservative decongestive treatment of BCRL’ can be stated. If the current study fails to prove an additional value of fluoroscopy-guided MLD or traditional MLD to placebo MLD, then MLD may be omitted from the decongestive lymphatic therapy. If MLD is omitted, a large reduction in therapy burden and a large reduction in social services costs can be achieved. If fluoroscopy-guided MLD is equally effective than traditional MLD and both are more effective than placebo MLD, traditional MLD has to be continued. Less expenses have to be made for the reimbursement of lymphofluoroscopic investigations.”