Prophylactic LYMphatic Reconstruction (LYMbR) to Prevent Lymphedema After Node Dissection for Cutaneous Malignancies
NCT ID: NCT05136079
Last Updated: 2021-11-26
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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NOT_YET_RECRUITING
PHASE3
40 participants
INTERVENTIONAL
2022-01-31
2025-12-31
Brief Summary
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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.
Detailed Description
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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.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
PREVENTION
DOUBLE
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.
Study Groups
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Prophylactic lymphaticovenous anastomosis
Intervention participants will undergo prophylactic lymphaticovenous anastomosis as an addendum to axillary or ilioinguinal lymphadenectomy for treatment of cutaneous malignancy.
Prophylactic lymphaticonvenous anastomosis
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.
Lymphadenectomy without lymphaticovenous anastomosis
Control participants will undergo axillary or ilioinguinal lymphadenectomy without lymphaticovenous anastomosis for treatment of cutaneous malignancy .
No interventions assigned to this group
Interventions
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Prophylactic lymphaticonvenous anastomosis
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.
Eligibility Criteria
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Inclusion Criteria
Exclusion Criteria
* 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
18 Years
ALL
No
Sponsors
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University of Calgary
OTHER
Tom Baker Cancer Centre
OTHER
Alberta Health Services, Calgary
OTHER
Responsible Party
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Claire Temple-Oberle
Surgeon, Departments of Surgery and Oncology; Professor - University of Calgary
Principal Investigators
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Claire Temple-Oberle, MD, MSc, FRCSC, MMEd
Role: PRINCIPAL_INVESTIGATOR
University of Calgary
Locations
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Foothills Medical Centre
Calgary, Alberta, Canada
Countries
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Central Contacts
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Facility Contacts
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Carmen Webb, MA
Role: primary
References
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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.
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.
Campanholi LL, Duprat JP, Fregnani JHTG. Incidence of le due to treating cutaneous melanoma. J Lymphoedema. 2011; 16(1): 30-34.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Other Identifiers
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PLVA-2021
Identifier Type: -
Identifier Source: org_study_id