Blood and Lymph Conditions

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Lymphedema

Skin Neoplasms

Lymphatic Diseases

Skin Diseases

Intervention participants will undergo prophylactic lymphaticovenous anastomosis as an addendum to axillary or ilioinguinal lymphadenectomy for treatment of cutaneous malignancy.

Control participants will undergo axillary or ilioinguinal lymphadenectomy without lymphaticovenous anastomosis for treatment of cutaneous malignancy .

Prophylactic lymphaticovenous anastomosis is an immediate prophylactic approach whereby the lymphaticovenous anastomosis is performed at the time of nodal dissection utilizing fluorescing indocynanine green (ICG) and an operating microscope.

Prophylactic lymphaticonvenous anastomosis

Carmen Webb, MA

Claire Temple-Oberle, MD, MSc, FRCSC, MMEd

Background: Lymphedema following lymph node dissection is a chronic condition that can limit physical, occupational, and social participation, impact self-image, and result in financial burden. Studies have reported lymphedema incidence rates of 39% to 73% following node dissection.

Lymphaticovenous anastomosis (LVA) has been previously used to treat established lymphedema. More recently, with imaging capabilities guided by blue dye and indocyanine green dye, the possibility of prophylactic LVA has become feasible. A 2018 systematic review of 12 studies utilizing prophylactic LVA during lymphadenectomy indicated a 2/3 reduction in the risk of lymphedema. The literature yet lacks any phase III studies with stringent controls and long term follow-up.

Objectives: To assess (primary endpoint) the impact of prophylactic LVA on presence or absence of lymphedema post axillary or groin lymphadenectomy and participant quality of life. To assess (secondary endpoint) the incidence of complications related to nodal dissection.

Methods: This is a phase III RCT, block randomized for upper and lower extremities, recruiting adult patients planned for an axillary or groin node dissection as a result of cutaneous malignancy. Analysis of rates of lymphedema and quality of life reports will be done.

Significance: Lymphedema is a feared outcome of surgical cancer care. Its impact on patients' daily lives is profound. A reduction of incidence of this debilitating condition by 2/3 would have significant impact on numerous lives and could also reduce the health system resources needed for its management.

Trial Objective: To ascertain the efficacy and impact of prophylactic lymphaticovenous anastomosis for prevention of lymphedema in cutaneous malignancy patients undergoing axillary or groin node dissection as part of cancer treatment. To determine quality of life impact, if any, for patients who receive this treatment. To determine incidence of complications related to nodal dissection are reduced with LVA.

Cancer-related lymphedema (CRLE) is a complex and lifelong implication of cancer treatment. Centres have reported rates of lymphedema following axillary node dissection of 39% (53% following adjuvant radiotherapy), and exceeding 73% following groin node dissection. Lymphedema can have significant quality of life (QoL) implications. Treatment, though helpful, is often burdensome, can require a second party to accomplish, and can be financially draining. Further, lymphedema is a chronic condition that cannot be eliminated once established. Many everyday activities, including self-care, employment, and social participation, as well as self-image, can be negatively impacted.

Given the high prevalence of CRLE, there is an urgency to investigate prophylaxis where possible. Prophylactic lymphaticovenous anastomosis offers this opportunity.

Although lymphaticovenous anastomosis (LVA) has been used for decades to treat existing lymphedema, more recently prophylactic LVA has been explored. Jørgensen et al's 2018 systematic review of 12 studies utilizing prophylactic LVA in cancer patients undergoing axilla or groin lymphadenectomy indicated a 2/3 reduction of CRLE in those treated prophylactically compared to those who did not receive prophylactic treatment.

More recently, Cakmakoglu et al reported on an immediate prophylactic approach whereby the LVA is performed at the time of nodal dissection utilizing fluorescing indocynanine green (ICG) and an operating microscope. This approach aided identification and assessment of the viability of lymphatic vessels in 96% of study cases, thereby augmenting the surgeon's ability to identify and choose the most appropriate vessels. Cakmakoglu's team performed the technique successfully on 22 patients. Of this 22, a single patient developed CRLE during the follow-up period (3 patients died of disease during the follow-up period but showed no sign of CRLE at their demise).

The outlook for LVA in combination with ICG looks promising but, to date, there has not been a Randomized Control Trial (RCT) on this prophylactic LVA technique. Thus, there is a need for robust RCTs utilizing a control group, having clearly defined outcome measures, investing in a significant follow-up period, and integrating blinded assessment in order to objectively demonstrate the impact of prophylactic LVA for patients.

Jørgensen et al's 2018 systematic review of prophylactic LVA case series and studies noted that, while the results were remarkable, the studies collected for the review did not have adequate control for bias and were quite heterogeneous in their cancer type, lymphadenectomy location, lymphedema classification, and assessment measures. QoL measures were not regularly integrated into assessment. Follow-up times varied from 6 months to 69 months with only 3 studies following for a minimum of 24 months.

Trial description:

Study participants will be comprised of patients undergoing lymphadenectomy for cutaneous malignancy. The participants will be block (axilla, groin) randomized using 2 equal groups (control/intervention) of 20 participants each. Participants assigned to the intervention arm will undergo prophylactic LVA as an addendum to their lymph node dissection. This will take place at time of lymphadenectomy surgery. Control participants will not have prophylactic LVA. Both groups will be blinded to treatment.

All participants will have limb volume measurements and photographs taken and the LYMQOL lymphedema-specific quality of life questionnaire administered at baseline (date of surgery) and at 6 month intervals for 24 months. Their recovery and surgical complications will be monitored as per the surgeon's usual followup schedule. At 24 months each participant will undergo a radionuclide lymphoscintigraphy to assess function and health of their lymphatic system. Unblinding will taken place at this juncture except in cases where necessary to unblind earlier to provide exceptional care.

A total of 40 study participants will be block (axilla, groin) randomized using 2 equal groups (control/intervention) of 20 participants each.

Participant: Participants will not be informed of their study arm allocation until they complete the study. Regardless of study arm, participants will be injected with the requisite blue dye to perform the LVA procedures, thereby providing no visible clue as to whether they are control or intervention participants. The exception will be in the case where a participant is diagnosed with lymphedema post-operatively but prior to their study participation completion and their healthcare management requires knowledge of surgical history.

Radiologist: At 24 months each participant will undergo a radionuclide lymphoscintigraphy to assess the functioning of the lymphatic system. The radiologist reading the results will be blinded as to the participants' study allocation.

Prophylactic LYMphatic Reconstruction (LYMbR) to Prevent Lymphedema After Node Dissection for Cutaneous Malignancies

Prophylactic LYMphatic Reconstruction (LYMbR) to Prevent Lymphedema

Using a non-stretch measuring tape, circumferential measurements at 4cm intervals along the length of the contralateral limbs will be taken pre-surgery (baseline) and at 24 months. Limb volumes will be calculated. In the limb impacted by surgery, a 10% increase in volume from baseline to 24 months will be indicative of the development of lymphedema. In the case of significant weight gain or loss, comparison with the volume of the contralateral limb will also be used to evaluate presence of lymphedema in the surgical limb.

A lymphedema quality of life patient reported outcome measure with specific arm and leg questionnaires called the LYMQOL will be used to measure quality of life. The scale uses a 4 point system for the majority of questions wherein a higher score indicates that lymphedema is having a greater negative impact on quality of life. A single final question uses a 10 point scale (poor to excellent) to rate one's quality of life overall with a higher score indicating greater quality of life. Comparison of quality of life scoring from baseline (pre-surgery) with scoring at 24 months post-surgery.

Diagnosis of complications such as cellulitis, dehiscence, lymphocele, and/or prolonged need for drain over 30days

University of Calgary

Tom Baker Cancer Centre

Alberta Health Services, Calgary

Surgeon, Departments of Surgery and Oncology; Professor - University of Calgary

Face-to-face consultation in Rehabilitation for early detection of lymphedema after surgery. Lower Limb measurement and care education

The usual follow-up will be carried out in GO consultation (0,1,6,12 months)

Face-to-face consultation in Rehabilitation for early detection of lymphedema after surgery (1,6,12 months). Lower Limb measurement and care education

Early lymphedema detection

Usual follow-up carried out in GO consultation

Usual follow-up

IBON JAUNARENA

This study aims to detect and treat early lower limb lymphedema secondary to lymphadenectomy with the aim of increasing the quality of life of patients with this chronic condition.

To this end, a group of patients (treatment group) will be referred to the Rehabilitation service for a previous consultation and after surgery where lymphedema could be detected early. In addition, the usual follow-up will be carried out in Gynecology Oncology consultation (GO). In the second group, also called control, will be performed the usual follow-up in GO.

For this we randomize to one of these two groups. The research project has the favorable report of the Center's Clinical Research Ethics Committee

METHODOLOGY:

1. Type of study: A) Randomized clinical trial B) Prospective cohort observational study
2. Study period: from January 2017 to December 2017.
3. Scope: health area of the province of Gipuzkoa and the University Hospital of Donostia as a reference center.
4. Selection of the population:

   4.1. The inclusion criteria will be: A) Diagnostic gynecological cancer patients submitted to bilateral laparoscopic pelvic lymphadenectomy as laparotomics (B: Sentinel Node Biopsy study, SNB) within the usual surgical protocol, with expected survival greater than 12 weeks and adequate liver, renal and medullary functions to accept And sign informed consent 4.2. The exclusion criteria for the study will be: Blood clotting or hematological disorders, previous thromboembolic disease and history of lymphatic system disease (lymphedema or lymphocele), contraindication for physiotherapy or who do not wish to participate and / or do not sign informed consent.

   4.3. Sample size: A) Assuming that according to previous studies the overall incidence of lymphedema after LPL is 21% (Hareyama et al), its estimated that a minimum sample of 44 patients will bi needed in order to be able to demonstrate at least 4-fold detection (Torres et al) of Lymphedemas with early follow-up with alpha = 0.05 and beta = 0.2, estimating that habitual follow-up detects 13% of lymphedema ( Mohler III et al).

   4.4. Recruitment Process: Will be selected consecutively and offered to participate in the study.
5. 5.1 Intervention: A) After diagnosis and programming for surgery at the GO consultation, circometry is performed by a trained nurse. During the admission, the nurse delivers and explains recommendations sheet and is offered to participate in the clinical trial giving him the Informed Consent (IC) and Information Sheet created for this purpose. In case of accepting and signing the IC, it is randomized (total randomization) according to system of envelopes with code.

Distribution of the intervention;

* Treatment group: Face-to-face consultation in Rehabilitation for early detection of lymphedema after surgery (1,6,12 months). Lower Limb measurement and care education
* Control group: The usual follow-up will be carried out in GO consultation (0,1,6,12 months)

The pelvic lymphadenectomy will be performed by the same surgical team using a transperitoneal approach. The limits of lymph node dissection will be: the psoas muscle, laterally, the postero-medially internal iliac artery, the bifurcation of the common iliac artery cranially, where it crosses the ureter, and caudally the origin of the epigastric vessels, to level of the deep circumflex iliac vein.

B) After diagnosis and programming for surgery at the GO consultation, circometry is performed by trained and yearly nurse. During the entrance, it is delivered and explains the recommendations sheet. SNB is performed by detecting sentinel ganglion from the above mentioned areas according to the protocol of the service. The usual follow-up will be carried out in GO consultation (0,1,6,12 months)

Recruitment Process: patients will be selected consecutively and offered to participate in the study

randomization according to system of envelopes with code

Early Detection of Lower Extremity Lymphedema After Lymphadenectomy in Gynecological Cancer

Study to Evaluate the Efficacy of Early Detection of Lower Extremity Lymphedema After Lymphadenectomy in Gynecological Cancer and Implantation of the Protocol

Lower Limb measurement secondary to lymphadenectomy in gynecological cancer

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Prophylactic LYMphatic Reconstruction (LYMbR) to Prevent Lymphedema After Node Dissection for Cutaneous Malignancies	NCT05136079	Lymphedema of L... Malignant Skin ...	Prophylactic ly...	18 Years -	Alberta Health Services, Calgary
Prophylactic LYMphatic Reconstruction (LYMbR) to Prevent Lymphedema After Node Dissection for Cutaneous Malignancies	NCT05136079	Lymphedema of L... Malignant Skin ...	Prophylactic ly...	18 Years -	Alberta Health Services, Calgary
Early Detection of Lower Extremity Lymphedema After Lymphadenectomy in Gynecological Cancer	NCT03917771	Lymphedema of L... Sentinel Lymph ...	Early lymphedem... Usual follow-up	18 Years - 85 Years	Hospital Donostia

Spots Global Cancer Trial Database for lymphedema of limb