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

NCT05136079 | Unknown Phase 3

• 1 other identifier: PLVA-2021
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Lymphedema of Limb; Malignant Skin Neoplasm

Outcome Measures

Primary Outcomes (2)

• Presence or absence of lymphedema at 24 months post axillary or groin lymphadenectomy as assessed by limb volume over time.

  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.

  24 months

• Quality of life impact as measured by LYMQOL PROM

  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.

  24 months

Secondary Outcomes (1)

• Incidence of evidence of acute post-operative surgical complications

  24 months

Study Arms (2)

Prophylactic lymphaticovenous anastomosis

EXPERIMENTAL

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

Procedure: Prophylactic lymphaticonvenous anastomosis

Lymphadenectomy without lymphaticovenous anastomosis

NO INTERVENTION

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

Interventions

Prophylactic lymphaticonvenous anastomosis PROCEDURE

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 lymphaticovenous anastomosis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult persons (\>18 years of age) undergoing axilla or groin lymphadenectomy as part of cutaneous malignancy management.

You may not qualify if:

• Patients receiving a sentinel lymph node biopsy alone
• Patients with untreated in-transit disease on the upper or lower extremities
• Patients with established preoperative lymphedema
• Patients with post-thrombotic syndrome
• Pregnant patients
• Patients with a previous history of radiation therapy to the affected nodal basin or extremity

Sponsors & Collaborators

• Alberta Health Services, Calgary: lead
• University of Calgary: collaborator
• Tom Baker Cancer Centre: collaborator

Study Sites (1)

Foothills Medical Centre

Calgary, Alberta, T2N 2T9, Canada

Location

Related Publications (17)

• Cakmakoglu C, Kwiecien GJ, Schwarz GS, Gastman B. Lymphaticovenous Bypass for Immediate Lymphatic Reconstruction in Locoregional Advanced Melanoma Patients. J Reconstr Microsurg. 2020 May;36(4):247-252. doi: 10.1055/s-0039-3401829. Epub 2019 Dec 31.

  PMID: 31891946 BACKGROUND

• Rockson SG. Causes and consequences of lymphatic disease. Ann N Y Acad Sci. 2010 Oct;1207 Suppl 1:E2-6. doi: 10.1111/j.1749-6632.2010.05804.x.

  PMID: 20961302 BACKGROUND

• Campanholi LL, Duprat JP, Fregnani JHTG. Incidence of le due to treating cutaneous melanoma. J Lymphoedema. 2011; 16(1): 30-34.

  BACKGROUND

• Paskett ED, Dean JA, Oliveri JM, Harrop JP. Cancer-related lymphedema risk factors, diagnosis, treatment, and impact: a review. J Clin Oncol. 2012 Oct 20;30(30):3726-33. doi: 10.1200/JCO.2012.41.8574. Epub 2012 Sep 24.

  PMID: 23008299 BACKGROUND

• Loprinzi PD, Cardinal BJ, Winters-Stone K, Smit E, Loprinzi CL. Physical activity and the risk of breast cancer recurrence: a literature review. Oncol Nurs Forum. 2012 May 1;39(3):269-74. doi: 10.1188/12.ONF.269-274.

  PMID: 22543385 BACKGROUND

• Baibergenova A, Drucker AM, Shear NH. Hospitalizations for cellulitis in Canada: a database study. J Cutan Med Surg. 2014 Jan-Feb;18(1):33-7. doi: 10.2310/7750.2013.13075.

  PMID: 24377471 BACKGROUND

• Tiwari P, Coriddi M, Salani R, Povoski SP. Breast and gynecologic cancer-related extremity lymphedema: a review of diagnostic modalities and management options. World J Surg Oncol. 2013 Sep 22;11:237. doi: 10.1186/1477-7819-11-237.

  PMID: 24053624 BACKGROUND

• Dunberger G, Lindquist H, Waldenstrom AC, Nyberg T, Steineck G, Avall-Lundqvist E. Lower limb lymphedema in gynecological cancer survivors--effect on daily life functioning. Support Care Cancer. 2013 Nov;21(11):3063-70. doi: 10.1007/s00520-013-1879-3. Epub 2013 Jun 29.

  PMID: 23812496 BACKGROUND

• Brayton KM, Hirsch AT, O Brien PJ, Cheville A, Karaca-Mandic P, Rockson SG. Lymphedema prevalence and treatment benefits in cancer: impact of a therapeutic intervention on health outcomes and costs. PLoS One. 2014 Dec 3;9(12):e114597. doi: 10.1371/journal.pone.0114597. eCollection 2014.

  PMID: 25470383 BACKGROUND

• Gebruers N, Verbelen H, De Vrieze T, Coeck D, Tjalma W. Incidence and time path of lymphedema in sentinel node negative breast cancer patients: a systematic review. Arch Phys Med Rehabil. 2015 Jun;96(6):1131-9. doi: 10.1016/j.apmr.2015.01.014. Epub 2015 Jan 28.

  PMID: 25637862 BACKGROUND

• Hormes JM, Bryan C, Lytle LA, Gross CR, Ahmed RL, Troxel AB, Schmitz KH. Impact of lymphedema and arm symptoms on quality of life in breast cancer survivors. Lymphology. 2010 Mar;43(1):1-13.

  PMID: 20552814 BACKGROUND

• Jorgensen MG, Toyserkani NM, Sorensen JA. The effect of prophylactic lymphovenous anastomosis and shunts for preventing cancer-related lymphedema: a systematic review and meta-analysis. Microsurgery. 2018 Jul;38(5):576-585. doi: 10.1002/micr.30180. Epub 2017 Mar 28.

  PMID: 28370317 BACKGROUND

• Garza RM, Chang DW. Lymphovenous bypass for the treatment of lymphedema. J Surg Oncol. 2018 Oct;118(5):743-749. doi: 10.1002/jso.25166. Epub 2018 Aug 11.

  PMID: 30098298 BACKGROUND

• Hanson SE, Chang EI, Schaverien MV, Chu C, Selber JC, Hanasono MM. Controversies in Surgical Management of Lymphedema. Plast Reconstr Surg Glob Open. 2020 Mar 27;8(3):e2671. doi: 10.1097/GOX.0000000000002671. eCollection 2020 Mar.

  PMID: 32537335 BACKGROUND

• Jonsson EL, Fraser Hill WK, Saayman M, Yakaback S, Assadzadeh GE, Gregory McKinnon EJ, Temple-Oberle C. Pilot Study of Immediate Lymphatic Reconstruction (ILR) During Lymph Node Dissection for Node-Positive Melanoma: Feasibility, Safety, and Early Outcomes. J Surg Oncol. 2026 Jan;133(1):46-53. doi: 10.1002/jso.70127. Epub 2025 Nov 5.

  PMID: 41190591 DERIVED

• Temple-Oberle C, Nicholas C, Rojas-Garcia P. Current Controversies in Melanoma Treatment. Plast Reconstr Surg. 2023 Mar 1;151(3):495e-505e. doi: 10.1097/PRS.0000000000009936. Epub 2023 Feb 23.

  PMID: 36821575 DERIVED

• Deban M, Vallance P, Jost E, McKinnon JG, Temple-Oberle C. Higher Rate of Lymphedema with Inguinal versus Axillary Complete Lymph Node Dissection for Melanoma: A Potential Target for Immediate Lymphatic Reconstruction? Curr Oncol. 2022 Aug 11;29(8):5655-5663. doi: 10.3390/curroncol29080446.

  PMID: 36005184 DERIVED

MeSH Terms

Conditions

Skin Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

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

  University of Calgary

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Carmen Webb, MA

CONTACT

403-521-3012; carmen.webb@ahs.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Surgeon, Departments of Surgery and Oncology; Professor - University of Calgary

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

Study Record Dates

• First Submitted: November 2, 2021
• First Posted: November 26, 2021
• Study Start: January 1, 2022
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: November 26, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)