Effectiveness of Fluoroscopy-guided MLD for Treatment of BCRL

= 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

Time frame: Primary endpoint = After 3 weeks of intensive treatment

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

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

Time frame: Primary endpoint = After 3 weeks of intensive treatment

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

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

Time frame: After 3 weeks of intensive treatment, 1, 3, 6 months of maintenance treatment and 6 months of follow-up

Population: 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%).

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.

Time frame: After 3 weeks of intensive treatment, 1, 3, 6 months of maintenance treatment and 6 months of follow-up

Population: 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%).

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

Time frame: After 3 weeks of intensive treatment, 1, 3, 6 months of maintenance treatment and 6 months of follow-up

Population: 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%).

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

Time frame: After 3 weeks of intensive treatment phase, after 1, 3, 6 months of maintenance treatments and after 6 months of follow-up

Population: 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%).

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).

Time frame: After 3 weeks of intensive treatment and 6 months of maintenance treatment

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.

Time frame: Between baseline and the end of the follow-up phase (12 months)

Population: 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%).

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.

Time frame: Between baseline and the end of the follow-up phase (12 months)

Population: between baseline and the end of the follow-up phase,12 patients were lost-to-follow up in total (or 6%).

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

Time frame: Between baseline and the end of the follow-up phase (12 months)

Population: 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%).

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.

Time frame: After 3 weeks of intensive treatment, 1, 3, 6 months of maintenance treatment and 6 months of follow-up

Population: 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%).

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

Time frame: After 3 weeks of intensive treatment and 1, 3, 6 months of maintenance treatment and 6 months of follow-up

Population: 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%).

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

Time frame: After 3 weeks of intensive treatment and 6 months of maintenance treatment and 6 months of follow-up

Population: 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%).

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

Time frame: After 3 weeks of intensive treatment, 1, 3, 6 months of maintenance treatment and 6 months of follow-up

Population: 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%).