Blood and Lymph Conditions

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Lymphedema

Breast Neoplasms

Edema

Breast Cancer Lymphedema

Breast Diseases

Skin Diseases

Lymphatic Diseases

Postoperative Complications

Compression bandages applied with low pressure (20-30 mmHg)

Compression bandages applied with low pressure (45-55 mmHg)

both group received complex decongestive physiotherapy consist of manual lymph dranaige, skin care, exercise and compression bandage. Every component except compression bandage applied exacly the same to both group. Compression bandage applied with low bandage interface pressure (20-30 mmHg)

complex decongestive physiotherapy with low pressure compression bandage

complex decongestive physiotherapy consist of manual lymph dranaige, skin care, exercise and compression bandage. Every component except compression bandage applied exacly the same to both group. Compression bandage applied with high bandage interface pressure (45-55 mmHg)

complex decongestive physiotherapy with high pressure compression bandage

elif duygu yıldız, Dr

The goal of this randomised comparison study is to compare different bandage interface pressures in individuals with breast cancer related lymphedema

The main questions it aims to answer are:

* Is high or low bandage pressure effective in reducing edema and soft tissue thickness?
* do bandages applied with high or low bandage pressure comprimise sleep, comfort or subjective benefit from treatment?

Participants will recieve complex decongestive physiotherapy. Bandage will apply high or low pressure. Effects of high and low bandage interface pressures will compare

The aim of this study was to evaluate the effect of compression bandage applied with different pressures on skin and subcutaneous thickness in individuals with breast cancer-related lymphedema.

individuals with stage 2 unilateral lymphedema participated in the study. Skin and subcutaneous thicknesses, extremity volumes, sleep quality, treatment benefit, comfort during treatment were evaluated respectively by ultrasound from 6 reference points as dorsum of hand, wrist volar, forearm dorsum, forearm volar, arm dorsum, arm volar, volumetric measurement, Pittsburgh Sleep Quality Index, Patient Benefit Index-Lymphedema, and visual analog scale. Complex decongestive physiotherapy was applied to individuals randomly divided into two groups: low (20-30 mmHg) and high bandage pressure (45-55 mmHg). Individuals were evaluated before treatment, at 1st, 10th session, end of treatment, and at 3 months follow-up.

radiologist who assessed soft tissue thickness assessment is masked and the patients did't know which group they belong to.

Effect of Different Bandage Interface Pressures on Breast Cancer Related Lymphedema

The Effect of Complex Decongestive Physiotherapy Applied With Different Compression Pressures on Skin and Subcutaneous Tissue Thickness in Individuals With Breast Cancer-related Lymphedema: a Double-blinded Randomized Comparison Trial

Evaluation of skin and subcutaneous tissue thickness and US evaluations were made by a radiologist using a 6-15 MHz linear probe with a LOGIQ US system. Skin and subcutaneous thickness were recorded as milimeter.

Limb volume was determined by the overflowing water method. The volumetric vessel was filled with tap water up to the overflow point of the vessel. Subjects were asked to lean forward while standing and slowly dip their arms into the water until the bar at the base of the volumetric cup snapped between the 2nd and 3rd fingers. During immersion, he was asked to avoid movements that could increase the transport of water. The overflowing water was first taken into a container. Then, the overflow water was calculated by transferring it to the measuring cups. The amount of overflowing water was recorded in ml. Measurements were made bilaterally.

Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). The scale that determines sleep quality consists of 18 questions and evaluates sleep quality in the last four weeks. PSQI has 7 components, and each component is evaluated between 0-3 points. The total score ranges from 0-21 (206). A total score higher than 5 indicates poor sleep quality (28). The sub-dimensions of PSQI are subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, use of sleeping pills, and daytime dysfunction

Patient comfort was evaluated with Visual Analogue Scale at the end of the treatment. It was explained to the individual that 0 point of a 10 cm line represents minimum comfort and 10 point represents maximum comfort. The individual was asked to mark the level of comfort he perceived during the treatment. The point marked by the individual was measured with a ruler and recorded in cm.

The benefit from the treatment was evaluated with the Patient Benefit Index-Lymphedema. It consists of two five-point Likert-type questionnaires containing the same 23 questions, the Patient Needs Questionnaire, and the Patient Benefit Questionnaire. Scores of Index are between 0-4. "0" means no benefit from treatment. "4" means maximum benefit from treatment.

score

Abant Izzet Baysal University

Research assistant

Nervous System Diseases

Peripheral Nervous System Diseases

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Single group, same patient, Homolateral wearing of cryotherapy devices only on hands and feet

Single group, same patient, Homolateral wearing of cryotherapy and compression devices on hands and feet

Self-controlled trial with only standard cryotherapy. Compression glove and foot sock will only be worn on one hand and one leg on the same side allocated by randomisation

cryotherapy alone of the upper or lower limbs

Self-controlled trial adding compression to standard cryotherapy. Compression glove and foot sock will only be worn on one hand and one leg on the same side allocated by randomisation

cryotherapy and crompression of the upper or lower limbs

Colin DEBAIGT, PhD

Clément DEVIC, PhD

Caroline BAILLEUX

Breast cancer is the most frequently diagnosed cancer in the world. In France, 58,000 new cases were detected in 2018. Breast cancer is therefore the most common cancer in women. The 5-year survival rate for all stages combined is 88%. These excellent survival figures have been achieved thanks to improvements in treatment, including the advent of chemotherapy. The majority of patients will be cured of their cancer, so post-cancer quality of life is a major issue, hence the importance of trying to reduce long-term sequelae.

Taxanes are one of the main cytotoxic anticancer agents used in the treatment of breast cancer. However, taxanes have a direct effect on the central and peripheral nervous systems and can induce chemotherapy-induced peripheral neuropathy (CIPN). The mechanisms of NPIC by taxanes are not fully understood. CINP is manifested by symptoms of paresthesia, numbness, burning, pain, altered temperature perception, myalgia, myopathy, fine motor difficulties, gait and balance disturbances, muscle weakness in the lower limbs and/or functional decline.

NPIC occurs in 80 to 97% of patients treated with taxanes and is the main limiting toxicity during paclitaxel administration. NPIC often leads to postponement or reduction of dose, or even discontinuation of treatment. In addition, NPIC may last for several months or even years after the end of anti-cancer chemotherapy and represents the main long-term sequelae. This can promote and/or exacerbate symptoms of psychological distress (depressive symptoms and symptoms of anxiety) and lead to a reduction in quality of life (QoL). Prevention of NIPC is therefore a major issue in breast cancer treatment. According to the 2014 guidelines from the American Society of Clinical Oncology, prevention and treatment of IPN are inadequate with current weapons, and there is an urgent need to evaluate and find new methods of prevention. One of the challenges in the management of NIPC will be to reduce the pain induced without diminishing the anti-tumour effect of anti-cancer agents.

In recent years, the effectiveness of cryotherapy using a frozen glove and compression therapy using surgical gloves (SG) in preventing taxane-induced PINC has been reported. During chemotherapy, patients wore a frozen glove on one hand and two surgical gloves of the same size on the other hand continuously. Recent study explained how compression therapy and cryotherapy shared a similar mechanism of reducing drug exposure due to vasoconstriction during paclitaxel infusion. The low temperature associated with cryotherapy would reduce paclitaxel uptake and peripheral nerve damage, or mechanotransduction, and allow a reduction in NIPC.

To date, no study has investigated the efficacy of combining the two means of prevention. The current standard at the Centre Antoine Lacassagne is cryotherapy. The aim of this prospective, self-controlled trial is therefore to compare the efficacy of cryotherapy combined with compression prevention versus cryotherapy alone in preventing paclitaxel-induced peripheral neuropathy in patients undergoing adjuvant treatment for localised breast cancer.

Open-label, single-centre, randomised (1:1), stratified, self-controlled cohort study

Comparison of the Efficacy of Cryotherapy Combined With Compression in Preventing Neuropathy

Comparison of the Efficacy of Cryotherapy Combined With Compression in Preventing the Development of Paclitaxel-induced Peripheral Neuropathy in Non-metastatic Breast Cancer: A Prospective, Single-centre, Self-controlled Trial

The limb with the highest grade of neuropathy will be given a score of 1 and the limb with the lowest grade of neuropathy a score of 0. If no neuropathy is identified in either of the 2 limbs, a score of 0 will be given for each limb. Finally, if a neuropathy of the same grade is identified in each of the 2 limbs, a score of 1 will be assigned for both limbs.

Success is defined as a differential of -1 in neuropathy score in favour of double prevention. This method will be applied to the primary and secondary endpoints.

Rate of discontinuation of cryotherapy during treatment

Comparison of the temperature measured between the upper and lower limbs (at extremity level) using an infrared thermometer

Percentage of patients with peripheral neuropathy for any limb according to the results of the DN4 questionnaire just before each treatment cycle

Thuasne

Centre Antoine Lacassagne

Weeks 1-12, Standard Care only (Compression Sleeve, daytime wear)

Weeks 1 - 12, Daytime compression sleeve plus night-time compression by self-administered or assisted multi-layered Compression Bandages.

Weeks 1 - 12, Standard care (day-time sleeve) plus night-time use of a custom-made Night-time Compression System Garment

Daytime compression sleeve plus night-time compression by self-administered or assisted multi-layered compression bandages.

Night-time compression bandages

Compression Sleeve, daytime wear

Standard Care plus night-time compression by a custom-made night time compression system garment.

Night-time Compression custom-made garment

Margaret McNeely, PhD

Lymphedema (significant arm swelling on the surgical side) is one of the most common complications following treatment for breast cancer. The impact of lymphedema is profound, resulting in negative self image, increased anxiety and poorer quality of life. In time, lymphedema can result in recurrent infections in the arm, functional impairment and pain. Approximately 21% of women who undergo breast cancer treatment develop lymphedema. Unfortunately this is a life-time condition which tends to worsen over time. Currently, treatment consists of intensive physiotherapy, meant to reduce the arm volume followed by the wearing of compression sleeves during the day for maintenance. This study hopes to show that the addition of night-time compression creates a measurable reduction in arm volume and that adding night-time compression to the standard care (daytime compression only) will produce improvements in quality of life for breast cancer survivors.

Lymphedema is a lifetime condition which tends to worsen over time, affecting roughly 21% of of treated breast cancer patients. An initial intensive rehabilitative treatment is usually prescribed to reduce the lymphedema, followed by a maintenance program using compression sleeves (Standard Care). However, compression sleeves are prescribed for daytime use only due to the potential tourniquet effect of the sleeve rolling up or bunching during the night.

Compression Bandages (short stretch, low elasticity) can be used at night but proper application takes 20-30 minutes, require skill to apply properly and are costly. Various types of night-compression system garments (NCSGs) have been designed as alternatives to Compression Bandages (CB).

The objectives of this study are to determine:

1. Whether the addition of night-time compression (using CB or NCSG) to standard care (daytime compression only) improves control of arm lymphedema.
2. Whether the use of NCSGs result in better outcomes in quality of life, sleep, treatment compliance and patient independence than use of Compression Bandages.

The hypotheses are that:

1. Standard care plus the addition of NCSG will provide statistically significant improvement in management of arm lymphedema volume compared to standard care alone at 12 weeks.
2. Standard care plus the addition of Compression Bandages will provide statistically significant improved management of arm lymphedema volume compared to standard care alone at 12 weeks.
3. Standard care plus the addition of NCSG will provide statistically significant benefit in quality of life, sleep and self-efficacy over standard care plus Compression Bandaging at 12 weeks.

Group 1: Standard care weeks 1 - 12 Group 2: Standard care plus night-time Compression Bandaging weeks 1 - 12 Group 3: Standard care plus night-time use of NCSG weeks 1 - 12

All three groups will adopt NCSG use after the 12 week assessments have been done (weeks 13 - 24).

Sample size = 40 participants per group, for a total of 120 patients at three sites.

Participants will be randomized in a 1:1:1 ratio to Standard, CB or NCSG using a secure central randomization service administered by the Clinical Trials Unit of the Cross Cancer Institute. Women enrolled in the study will be stratified by accruing site and by lymphedema severity (i.e. mild versus moderate lymphedema as per the classification criteria of the International Society of Lymphology).

Arm volume (by Perometer) and arm fluid (by Bioimpedance analysis) will be measured and compared to that of the unaffected arm. BIA measures the impedance of flow from a low alternating electrical current that is applied to the body through a skin electrode. BIA records impedance values for each limb and provides an index that correlates with quantitative measurements of volume increase in limb size seen in the arm with lymphedema. This measurement will provide information on extracellular fluid changes that complements the data on arm lymphedema volume. An Independent Assessor unaware of treatment allocation (blinded) will perform the measurements of arm volume using the perometer, bioimpedance analysis, and body weight at baseline, 6, 12, 18 and 24 weeks. The duration of the primary intervention will be 12 weeks. Following the 12-week intervention period, participants in the CB and standard care groups will be measured for a NCSG.

The follow-up period after the intervention (weeks 13 to 24) will follow a longitudinal observational design and provide an opportunity to examine factors related to long-term adherence to night-time compression. Lymphedema specific questionnaires and subject diary will be completed at 6, 12, 18 and 24 weeks to assess subject's Quality of Life, sleep disturbance, self-efficacy and treatment adherence.

Studying if Adding Night Compression to Standard Care Will Have Improved Control of Lymphedema in Breast Cancer Subjects

Night-time Compression for Breast Cancer Related Lymphedema (LYNC): A Randomized Controlled Efficacy Trial

All IPD that underlie results in a publication will be available via the University of Alberta's DATAVERSE platform.

Cross Cancer Institute

AHS Cancer Control Alberta

Neuromuscular Diseases

Antirheumatic Agents

Cyclophosphamide

Epirubicin

Cryotherapy will be applied using a frozen glove and sock for 15 minutes before, during and 15 minutes after each albumin-paclitaxel infusion. Compression therapy will be applied using a surgical glove for 30 minutes before, during and 30 minutes after each albumin-paclitaxel infusion.

ddEC-ddT will be administered without cryotherapy combined with compression.

Preparation of frozen glove and sock: 4℃ for 3 hours.

Frozen glove and sock

Epirubicin (E) 90\~100mg/m\^2, i.v., d1 + cyclophosphamide (C) 600 mg/m\^2, i.v., d1, q2w, for 4 cycles followed by albumin-paclitaxel (T) 260 mg/m\^2, i.v., d1, q2w, for 4 cycles.

ddEC-ddT

Zhaoqing Fan, MD

Lize Wang, MD

Zhaoqing Fan

This is a prospective, multi-center, randomized study designed to evaluate the clinical efficacy of cryotherapy combined with compression therapy in preventing albumin-paclitaxel induced peripheral neuropathy.

All HER-2 negative breast cancer patients received neoadjuvant chemotherapy with four cycles of dose-dense epirubicin and cyclophosphamide (ddEC) followed by four cycles of dose-dense albumin-paclitaxel (ddT). The patients were randomly assigned in a 1:1 ratio to receive cryotherapy combined with compression or no intervention. The primary endpoint was incidence of grade 3 and higher peripheral neuropathy as assessed by NCI-CTCAE V5.0.

Effectiveness of Cryotherapy Combined With Compression Therapy for Preventing Chemotherapy-induced Peripheral Neuropathy

Effectiveness of Cryotherapy Combined With Compression Therapy in Preventing Albumin-paclitaxel Induced Peripheral Neuropathy in Breast Cancer Patients

Incidence of grade 3 and higher peripheral neuropathy as assessed by NCI-CTCAE V5.0

Incidence of grade 2 and higher peripheral neuropathy as assessed by NCI-CTCAE V5.0

PNQ scale ranges from scores A to E; with scoring of A being not affected neuropathy, and E with the worst neuropathy.

The EORTC QLQ-CIPN20 is a fairly new 20-item questionnaire evaluating various aspects of CIPN. It has three subscales assessing sensory (nine items), motor (eight items), and autonomic (three items) symptoms and functioning with each item measured on an ordinal 1-4 scale (1, not at all; 4, very much).

Incidence and severity of other adverse events as assessed by NCI-CTCAE V5.0

Total pathological complete response (tpCR) was defined as the absence of invasive lesions in the breast and axillary lymph nodes (ypT0/is ypN0). The tpCR rate is the percentage of participants with tpCR.

Breast pathological complete response (bpCR) was defined as no invasive carcinoma in the breast (ypT0/is). The bpCR rate is the percentage of participants with bpCR.

The number of participants who achieved complete response and partial response at the end of neoadjuvant chemotherapy as a percentage of the overall evaluable participants.

Invasive disease free survival was defined as the time from enrollment until the date of first occurrence of one of the following events: invasive ipsilateral breast tumor recurrence, local/regional invasive recurrence, distant recurrence (including first metastasis), invasive contralateral breast cancer, second primary invasive cancer (nonbreast, not including squamous or basal cell skin cancers, or new in situ carcinomas of any site), or death from any cause.

CSPC Ouyi Pharmaceutical Co., Ltd.

Peking University

Director of Breast Center of Peking University Cancer Hospital

Remedial exercise program will be taught by qualified physiotherapist. Patients will be practiced to the exercise 3 sets of 15 repetitions without compression. Patients will be monitored telephonically in the washout period for remain the routine activities.

Remedial exercise

Multi-layered short stretch bandaging will be applied for 23 hour. Patients will be practiced to the exercise 3 sets of 15 repetitions with compression bandage. The bandage will be removed at the same time the next day. Patients will be monitored telephonically in the washout period for remain the routine activities.

Compression bandage

The aim of this study to investigate 24 hours of effects of remedial exercises with and without compression therapy on severity of lymphedema and symptoms of the lymphedema The present study is designed as a non-drug clinical trial. The patients will complete two remedial exercise sessions, one without and one with compression in a randomized order separated by a 3-day wash-out period.The main questions it aims to answer are

1. The 24 hour effects of remedial exercises with and without compression therapy on the severity of lymphedema are different in individuals with lymphedema associated with breast cancer surgery.
2. The 24 hour effects of remedial exercises with and without compression therapy on the symptoms of lymphedema are different in individuals with lymphedema associated with breast cancer surgery.

The 24 Hour Effects of Remedial Exercises With and Without Compression Therapy on Breast Cancer-related Lymphedema

Ultrasound imaging was performed using a 5-13-Megahertz linear probe. During the procedure, the participants will be seated with their forearms supinated and extended on a pillow. Measurements will be made bilaterally from 10 cm distal and proximal to the elbow bend, from the midpoint of the medial and lateral epicondyles, along the line parallel to the arm axis.

The severity of lymphedema between the two extremities will be measured by measuring the environment at 5 cm intervals.

The patient is in the supine position with his arms and legs not touching each other. This measurement will be made using the Impedimed L-Dex U 400 device. The reference point is the top of both hands and the dorsum of the foot. This measurement is made using superficial electrodes and there is no risk. The percentage of fluid will be calculated by making a measurement for both arms.

Four participant-reported lymphedema symptoms were assessed: swelling, heaviness, tightness commonly associated with BCRL. Using a 100 mm visual analogue scale (VAS), participants marked on it the extent to which they perceived their arm to be swollen, heavy or tight and pain during the past month, with 0 being "not at all" and 10 being "extremely".

Hacettepe University

Prof. Dr.

Wounds and Injuries

Skin Neoplasms

Anti-Infective Agents

Monensin

In this arm, investigators will use the PICO system (Smith and Nephew) for compression therapy after split thickness skin graft of leg ulcers.

In this arm, investigators will use the Coban 2 lite compression bandaging for compression therapy after split thickness skin graft of leg ulcers.

PICO

Coban 2 lite

Martina Kristiansen, MD

Elisabeth Valio Sætnan, MD

Thomas Moe Berg, MD, PhD

The single center, prospective, randomized trial includes in total 60 patients. We want to compare two different treatment methods for compression therapy for split thickness skin graft in lower leg. The patients are randomized to compression therapy with NPWT (negative pressure wound therapy) using the device PICO or using the compression bandage with Coban 2 lite.

Primary outcome is complete healing of the skin transplant 30 days postoperatively. Secondary outcomes will be to note frequency of infection, bleeding, loss of transplant etc.

Prospective, RCT of Split Thickness Skin Grafts on Lower Leg After Compression Therapy With Compression Bandage vs. NPWT

Prospective, Randomized Study of Split Thickness Skin Graft in Wounds on Lower Leg After Compression Therapy With Compression Bandage vs. NPWT

Numbers of patients with 100 % healing of the split thickness skin graft

Average healing of the split thickness skin grafts

Evaluate change in daily function after surgery

Oslo University Hospital

Antiemetics

Gastrointestinal Agents

Dimenhydrinate

Information, skin care, compression therapy, exercises and fluoroscopy-guided MLD 3 weeks (14 sessions of 60 minutes) of intensive treatment 6 months (18 sessions of 60 minutes) of maintenance treatment 6 months of follow-up

Information, skin care, compression therapy, exercises and traditional MLD 3 weeks (14 sessions of 60 minutes) of intensive treatment 6 months (18 sessions of 60 minutes) of maintenance treatment 6 months of follow-up

Information, skin care, compression therapy, exercises and placebo MLD 3 weeks (14 sessions of 60 minutes) of intensive treatment 6 months (18 sessions of 60 minutes) of maintenance treatment 6 months of follow-up

During intensive phase: a leaflet with information about the lymphatic system and lymphoedema, clinical evaluation and conservative treatment of lymphoedema During maintenance phase: two informational sessions about self-management and about compression sleeves and other compression material

Information

The skin is hydrated during the session. If wounds are present, the wound is cared.

Skin care

During intensive phase: application of multi-layer, multi-component bandages During maintenance phase: wearing custom-made compression garment

Compression therapy

Fluoroscopy-guided MLD is applied on patient-specific lymphatic system (known from lymphofluoroscopy) by applying cleaning techniques on lymph nodes, resorption techniques to stimulate resorption of lymph by lymph capillaries and gliding technique to stimulate transport of lymph through lymph collectors

Fluoroscopy-guided MLD

Traditional MLD is applied without knowledge of the patient-specific lymphatic architecture. During MLD no cream or oil is used. A pressure with the hands up to 40 mmHg is applied. Drainage is performed at the level of the jugular and occipital region and the belly (in the depth). Draining techniques are applied on the retroclavicular lymph nodes, axillary lymph nodes, humeral lymph nodes and cubital lymph nodes. At the level of the hand, arm, shoulder and trunk, hand movements are applied to stimulate lymphatic transport through the lymph collectors. The therapist's hands perform 'pumping-movements' while stretching the skin.

Traditional MLD

During placebo MLD a superficial massage with massage cream is performed on the patient's contralateral arm and on the belly.

Placebo MLD

Nele Devoogdt, PhD

The main scientific objective of this multicentric double-blinded randomised controlled trial entails examining the effectiveness of fluoroscopy-guided MLD versus traditional MLD versus placebo MLD, applied as part of the intensive and maintenance phase of Decongestive Lymphatic Therapy, for the treatment of BCRL Secondary scientific objectives entail examining the relationship between different variables of lymphoedema at baseline

According to the International Society of Lymphology, lymphoedema needs to be treated with Decongestive Lymphatic Therapy (Consensus Document ISL 2013). This is a two-stage treatment programme. During the first or intensive phase, lymphoedema has to be maximally reduced. This phase consists of skin care, manual lymph drainage (MLD), multi-layer bandaging and exercise therapy. The second or maintenance phase aims to conserve and optimise the results obtained in the first phase. It consists of skin care, compression by a low-stretch elastic sleeve, exercises and lymph drainage. Skin care, multi-layer bandaging, elastic sleeve and exercises are treatment modalities that (after instructing the patient) can be performed by the patient herself. MLD has to be applied by a physical therapist and hence entails a big financial cost for the patient and the Health Care (Kärki et al 2009). The effectiveness of MLD applied during the intensive phase has been investigated by 5 randomised controlled trials, but there is conflicting evidence. So, further investigation is warranted to determine the relative benefit of MLD. The effectiveness of MLD applied during the maintenance phase has never been investigated (Devoogdt et al 2010, Oremus et al 2012, Huang et al 2013, Ezzo et al 2015).

A possible explanation why MLD is not obviously proven to be effective, is that MLD is applied in an inefficient way: during MLD, hand manoeuvres are applied on all lymph nodes and lymphatics that may be anatomically present. After axillary dissection and/ or radiotherapy (for the treatment of breast cancer), the lymphatic system is damaged: lymph nodes are removed and often fibrosis of the superficial lymphatic system occurs. As a result, rerouting of the lymphatic drainage occurs. Rerouting is patient-specific, consequently, it is possible that the traditional MLD needs be abandoned and a tailored approach needs to be established. Lymphofluoroscopy can aid to apply a more efficient MLD. During lymphofluoroscopy, a fluorescent substance is injected subcutaneously in the hand and it visualizes the transport of lymph from the hand up to the axilla and it demonstrates alternative pathways towards other lymph nodes.

A second explanation why the traditional method of MLD is not proven to be effective, is that research has shown that MLD with high pressure (vs low pressure) is more effective to improve lymph transport, as well as gliding (vs no gliding). During the new method of MLD (or fluoroscopy-guided MLD), the therapist only performs hand movements on functional lymphatics and lymph nodes. In addition, the hand movements are applied with higher pressure and lymph transport through the lymph collaterals is stimulated by applying strikes across the skin.

Therefore, the main scientific objective entails examining the effectiveness of fluoroscopy-guided MLD versus traditional MLD versus placebo MLD, applied as part of the intensive and maintenance phase of Decongestive Lymphatic Therapy, for the treatment of BCRL

Effectiveness of Fluoroscopy-guided MLD for Treatment of BCRL

Effectiveness of Fluoroscopy-guided Manual Lymph Drainage (MLD) Versus Traditional MLD or Placebo MLD, as Part of Decongestive Lymphatic Therapy, for the Treatment of Breast Cancer-related Lymphoedema (BCRL): a Randomised Controlled Trial

= the ratio at the different time points; The (inter-limb) ratio = Relative excessive lymphoedema volume of the arm/ hand = \[(volume arm + volume hand affected side) / (corrected volume arm + corrected volume hand healthy side)\]; Volume arm is determined by performing circumference measurements and calculating the volume with the formula of the truncated cone; Volume hand is determined by the water displacement method; The volume of the non-dominant hand/arm is on average 3.3% smaller than the dominant hand/arm, therefore is the volume of the arm at the healthy side corrected for hand dominance

Ratio PWC% at the different time intervals

= PWC% affected side / PWC% healthy side Measured with the MoistureMeterD compact at the level of shoulder and trunk where after a mean ratio PWC% is calculated

L-Dex score, measured with Impedimed BIS device at the different time points Amount of extracellular fluid = represented by L-Dex score This outcome is calculated and displayed on the Impedimed BIS device, and represents the difference in the amount of extracellular fluid in the affected upper limb compared to the unaffected upper limb. Normal L-Dex scores range between -10 and +10. A score outside this range, represents lymphedema. A higher number, represents a worse score.

Analyses for change in thickness of cutis + subcutis were performed:

Relative excessive thickness of the cutis+subcutis (inter-limb ratio of cutis+subcutis in mm) = Thickness of cutis+subcutis (mm) affected side / thickness of cutis+subcutis (mm) healthy side Arm: Reference points 1, 2, 3, 5, 6, 7 where after a mean ratio thickness of cutis+subcutis is calculated

Different scores are obtained from the questionnaire. Each of the 29 questions has to be scored on a 11-point Likert scale between 0 and 10 (instead of a VAS between 0 and 100). The total score of the Lymph-ICF-UL is equal to the sum of the scores on the questions divided by the total number of answered questions and multiplied by 10. In addition, a score is determined for each of the five domains of the Lymph-ICFUL: (1) physical function, (2) mental function, (3) household activities, (4) mobility activities, and (5) life and social activities.

Thus, the total score on the Lymph-ICF-UL and the score on the five domains range between 0 and 100. The higher the score, the more problems in functioning.

Induration force is presented in Newton (N) by the device. Relative difference in skin elasticity (induration force inter-limb ratio) = Skin elasticity affected side / skin elasticity healthy side Arm: Reference points 1, 2, 3, 5, 6, 7 where after a mean induration ratio is calculated

At the end of each assessment, subjects are asked to fill in the questionnaire individually Questionnaire counts 16 + 1 questions, which relate to the following 5 domains: physical symptoms; physical wellbeing, psychological symptoms; existential wellbeing and support A Likert scale with 11 possibilities (0-10) is used for the 16 questions and part D is an open question Each question corresponds to a score between 0 (very bad) and 10 (excellent); a total score and 5 different domain scores are calculated (each between 0 and 10) A lower score indicates a lower Quality of Life

At each clinical evaluation, it was asked to the patient if they had had an episode of erysipelas (which is an infection) between today and the previous evaluation.

The numbers of episodes were counted, and the causes of this episode of erysipelas were described. The numbers of episodes were compared between the groups.

The number patients presented as a percentage that indicated that their complaints have been slightly (3), much (2) or very much improved (1) during 12 months of time

The mean rating of the perceived effect of the manual lymph drainage (MLD) that patients received during the study (between 0-10). The higher the score, the higher the satisfaction about the effect of the manual lymph drainage received.

Ratio PWC% at the different time intervals

= PWC% affected side / PWC% healthy side Measured with the MoistureMeterD compact at different measurement points where after a mean ratio PWC% is calculated Arm: Reference points 1, 2, 3, 5, 6, 7 where after a mean ratio PWC% is calculated

In total, six reference points (located at the hand (1 reference point) and arm (5 reference points)) are being evaluated and scored (0 or 1) A reference point is scored with 1 in case the skin fold thickness at the affected side is increased compared to the reference point at the non-affected side The final outcome for the arm score is the (cumulated) total score of six reference points 1, 2, 3, 5, 6, 7 (range 0-6), a higher score indicates more presence of thickened skin

In total, six reference points (located at the hand (1 reference point) and arm (5 reference points)) are being evaluated and scored (0 or 1) A reference point is scored with 1 in case fibrosis of the skin is present The final outcome for the arm score is the (cumulated) total score of six reference points 1, 2, 3, 5, 6, 7 (range 0-6), a higher score indicates more presence of fibrosis

1. Total dermal backflow score (0-39). The higher the score, the more dermal backflow is present
2. Amount of efferent lymphatics leaving dermal backflow areas
3. Presence of visible lymph nodes after the break

Raw data is currently still being analyzed in order to be able to report on the described outcome measures. At present (March 2022) these analyses are not yet performed. Therefore these results will be reported later on this year (anticipated date: July 2022).

Agentschap voor Innovatie door Wetenschap en Technologie

Universitaire Ziekenhuizen KU Leuven

Information, skin care, compression therapy, exercises and fluoroscopy-guided MLD 3 weeks (14 sessions of 60 minutes) of intensive treatment 6 months (18 sessions of 60 minutes) of maintenance treatment 6 months of follow-up

Information: During intensive phase: a leaflet with information about the lymphatic system and lymphoedema, clinical evaluation and conservative treatment of lymphoedema During maintenance phase: two informational sessions about self-management and about compression sleeves and other compression material

Skin care: The skin is hydrated during the session. If wounds are present, the wound is cared.

Compression therapy: During intensive phase: application of multi-layer, multi-component bandages During maintenance phase: wearing custom-made compression garment

Fluoroscopy-guided MLD: Fluoroscopy-guided MLD is applied on patient-specific lymphatic system (known from lymphofluoroscopy) by applying cleaning techniques on lymph nodes, resorption techniques to stimulate resorption of lymph by lymph capillaries and gliding technique to stimulate transport of lymph through lymph collectors

Information, skin care, compression therapy, exercises and traditional MLD 3 weeks (14 sessions of 60 minutes) of intensive treatment 6 months (18 sessions of 60 minutes) of maintenance treatment 6 months of follow-up

Information: During intensive phase: a leaflet with information about the lymphatic system and lymphoedema, clinical evaluation and conservative treatment of lymphoedema During maintenance phase: two informational sessions about self-management and about compression sleeves and other compression material

Skin care: The skin is hydrated during the session. If wounds are present, the wound is cared.

Compression therapy: During intensive phase: application of multi-layer, multi-component bandages During maintenance phase: wearing custom-made compression garment

Traditional MLD: Traditional MLD is applied without knowledge of the patient-specific lymphatic architecture. During MLD no cream or oil is used. A pressure with the hands up to 40 mmHg is applied. Drainage is performed at the level of the jugular and occipital region and the belly (in the depth). Draining techniques are applied on the retroclavicular lymph nodes, axillary lymph nodes, humeral lymph nodes and cubital lymph nodes. At the level of the hand, arm, shoulder and trunk, hand movements are applied to stimulate lymphatic transport through the lymph collectors. The therapist's hands perform 'pumping-movements' while stretching the skin.

Information, skin care, compression therapy, exercises and placebo MLD 3 weeks (14 sessions of 60 minutes) of intensive treatment 6 months (18 sessions of 60 minutes) of maintenance treatment 6 months of follow-up

Information: During intensive phase: a leaflet with information about the lymphatic system and lymphoedema, clinical evaluation and conservative treatment of lymphoedema During maintenance phase: two informational sessions about self-management and about compression sleeves and other compression material

Skin care: The skin is hydrated during the session. If wounds are present, the wound is cared.

Compression therapy: During intensive phase: application of multi-layer, multi-component bandages During maintenance phase: wearing custom-made compression garment

Placebo MLD: During placebo MLD a superficial massage with massage cream is performed on the patient's contralateral arm and on the belly.

Total

Age, Continuous

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

Belgium

Region of Enrollment

Body Mass Index

Prof. Nele Devoogdt

Baseline

Post intensive treatment phase

At the post-intensive assessment, 5 patients dropped-out of which 4 patients (2%) were lost to follow-up.

Lymphoedema Volume at the Level of the Arm/ Hand

Post intensive phase

Stagnation of Fluid at Level of the Shoulder/ Trunk

Post-intensive

1M maintenance

3M maintenance

6M maintenance

6M follow-up

At the post-intensive assessment, 5 patients dropped-out of which 4 patients (2%) were lost to follow-up. At the end of the maintenance phase (P6), only 3 additional patients (1.5%) were lost to follow-up. At the end of the follow-up phase (P12), one additional patient was lost to follow-up (12 patients in total since baseline or 6%).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Effect of Different Bandage Interface Pressures on Breast Cancer Related Lymphedema	NCT05660590	Lymphedema of U... Breast Cancer L... Edema Arm	complex deconge... complex deconge...	18 Years - 85 Years	Abant Izzet Baysal University
Comparison of the Efficacy of Cryotherapy Combined With Compression in Preventing Neuropathy	NCT06400849	Non-metastatic ...	cryotherapy alo... cryotherapy and...	18 Years - 99 Years	Centre Antoine Lacassagne
Studying if Adding Night Compression to Standard Care Will Have Improved Control of Lymphedema in Breast Cancer Subjects	NCT02187289	Breast Cancer Lymphedema	Night-time comp... Compression Sle... Night-time Comp...	-	AHS Cancer Control Alberta
Effectiveness of Cryotherapy Combined With Compression Therapy for Preventing Chemotherapy-induced Peripheral Neuropathy	NCT05341141	Breast Cancer	Frozen glove an... ddEC-ddT	20 Years - 70 Years	Peking University
The 24 Hour Effects of Remedial Exercises With and Without Compression Therapy on Breast Cancer-related Lymphedema	NCT05610579	Lymphedema, Bre...	Remedial exerci... Compression ban...	18 Years - 75 Years	Hacettepe University
Comparison of the Efficacy of Cryotherapy Combined With Compression in Preventing Neuropathy	NCT06400849	Non-metastatic ...	cryotherapy alo... cryotherapy and...	18 Years - 99 Years	Centre Antoine Lacassagne
Prospective, RCT of Split Thickness Skin Grafts on Lower Leg After Compression Therapy With Compression Bandage vs. NPWT	NCT03452852	Skin Cancer	PICO Coban 2 lite	18 Years -	Oslo University Hospital
Effectiveness of Cryotherapy Combined With Compression Therapy for Preventing Chemotherapy-induced Peripheral Neuropathy	NCT05341141	Breast Cancer	Frozen glove an... ddEC-ddT	20 Years - 70 Years	Peking University
The 24 Hour Effects of Remedial Exercises With and Without Compression Therapy on Breast Cancer-related Lymphedema	NCT05610579	Lymphedema, Bre...	Remedial exerci... Compression ban...	18 Years - 75 Years	Hacettepe University
Effectiveness of Fluoroscopy-guided MLD for Treatment of BCRL	NCT02609724	Breast Neoplasm Lymphedema	Information Skin care Compression the... Fluoroscopy-gui... Traditional MLD Placebo MLD	18 Years -	Universitaire Ziekenhuizen KU Leuven
Studying if Adding Night Compression to Standard Care Will Have Improved Control of Lymphedema in Breast Cancer Subjects	NCT02187289	Breast Cancer Lymphedema	Night-time comp... Compression Sle... Night-time Comp...	-	AHS Cancer Control Alberta

Spots Global Cancer Trial Database for compression therapy