Clinical trial NCT03073096: LYMPHA: Eliminating the Burden of Lymphedema in Patients Requiring Nodal Dissection
Official title: Performing a Lymphatic-venous Anastomosis at Time of Nodal Dissection in Patients Requiring Complete Axillary or Groin Dissection for the Prevention of Lymphedema
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Lymph Node Disease
Keywords: axillary nodal dissection
groin nodal dissection
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
First posted: 2017-03-08
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All melanoma and other skin cancers (merkel cell carcinoma, squamous cell carcinoma as well as sarcoma patients requiring a nodal dissection (groin or axillary) will be offered to have a LVA at time of nodal dissection to prevent lymphedema.
Primary purpose: PREVENTION

Brief summary: Lymphedema is the build-up of lymph fluid in the body's tissue causing chronic, debilitating swelling. This commonly occurs as a result of a disruption of the lymphatic system during lymph node dissection surgeries. In melanoma patients, the incidence of lymphedema ranges from 5-10% in the arms following an axillary dissection, and 28-40% in the legs following groin dissection. LYMPHA (LYmphatic Microsurgical Preventive Healing Approach) is an innovative microsurgical technique where blocked lymphatic vessels are drained into the blood circulation by surgically creating a shunt between a lymphatic channel and a blood vessel called a lymphatic-venous bypass. Recently, LYMPHA has been shown to prevent lymphedema when performed at the time of nodal dissection. We propose a prospective pilot study evaluating the practice of the LYMPHA technique for the primary prevention lymphedema at The Ottawa Hospital. The novel use of the LYMPHA technique holds the potential to prevent lymphedema rather than to attempt to treat it once it has already progressed and as a result will not only improve the quality of life of the cancer patients, but also decrease health care costs associated with treating lymphedema.

Detailed description: Consenting patients will have the LYMPHA procedure at the time of planned axillary or groin dissection surgery for the prevention of upper and lower extremity lymphedema, respectively. The node dissection will be performed by Dr. Nessim, while the LYMPHA technique will be performed by the plastic surgeon, Dr. Momtazi, trained in microsurgical technique. The LYMPHA procedure consists of performing lymphatic-venous anastomoses (LVA) at the time of the node dissection. Patent blue dye will be injected into the patient approximately 10 minutes before skin incision. This will allow mapping of the lymphatic channels for identification for bypass. The node dissection will then be performed with preservation of the saphenous vein in the leg and the anterior branch of the axillary vein in the axilla. Afferent lymphatic vessels will be sutured into the saphenous vein or a branch of the axillary vein distal to a competent valve, respectively. The total duration of the surgery is approximately 3 hours. The LYMPHA technique accounts for an additional 30 minutes to the standard 2-2.5 hours allocated to the node dissection.

Pre-surgery, patients will have baseline limb circumference measurements of both the surgery-affected and unaffected limbs (arms or legs). Patients will be followed up clinically at every 3 months up to a year, and then again at the end of the second year (at the 24 month-mark only). At each follow-up visit, patients will have a physical examination and their circumferential limb measurements will be taken with measuring tape at three specific intervals up the limb. For example, patients undergoing an axillary dissection will have the circumference of their wrist taken, and then again 4 cm proximal to the wrist, then 8 cm proximal to the wrist, and so forth. The method will be used for the legs but starting at the ankle. Volume will be calculated indirectly, using Dr. Brorson's truncated cone method (13). Patients will also fill out a limb lymphedema-specific quality of life questionnaire (LYMQOL) administered by the Clinical Research Coordinator pre- and post-surgery. Each patient will have a total of 2 years of participation time.

Pre-surgery, patients will have baseline limb circumference measurements of both the surgery-affected and unaffected limbs (arms or legs). Patients will be followed up clinically at every 3 months up to a year, and then again at the second year. At each follow-up visit, patients will have a physical examination and their circumferential limb measurements will be taken with measuring tape at three specific intervals up the limb. Patients will also fill out a limb lymphedema-specific quality of life questionnaire (LYMQOL) administered pre- and post-surgery.

1. Primary Objective: To evaluate the success rate of performing the LYMPHA procedure. Success is defined as a completed LYMPHA procedure i.e. successful LVA.
2. Secondary Objective: To evaluate the feasibility of follow-up assessments i. establish the ability to obtain pre- and post- limb measurements ii. obtain limb-specific quality of life information iii. design a protocol for a randomized controlled trial comparing lymphedema rates in patients receiving a lymphadenectomy + lymphatic-venous bypass versus lymphadenectomy alone.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed primary melanoma, soft tissue sarcoma, squamous cell carcinoma or merkel cell carcinoma of the trunk or chest.
* Node-positive cancer requiring an axillary or groin lymphadenectomy

Exclusion Criteria:

* Patients receiving a sentinel lymph node biopsy alone
* Patients with a cancer on the upper or lower extremities are excluded (i.e. arms or legs).
* Patients with established preoperative lymphedema
* Patients with post-thrombotic syndrome, peripheral vascular disease
* Pregnant patients

Primary outcomes:
measure: Difference in limb volume between surgery-affected and surgery-unaffected limb at baseline, 3, 6, 9, 12 and 24 months
timeFrame: every 3 months up to a year, again at year 2
Secondary outcomes:
measure: Limb-lymphedema-specific Quality of life assessment at baseline, 3, 6, 9, 12 and 24 months through the LYMQOL questionnaire
timeFrame: every 3 months up to a year, again at year 2
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
Study officials:
affiliation: The Ottawa Hospital
name: Carolyn Nessim, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Boccardo F, Casabona F, De Cian F, Friedman D, Murelli F, Puglisi M, Campisi CC, Molinari L, Spinaci S, Dessalvi S, Campisi C. Lymphatic microsurgical preventing healing approach (LYMPHA) for primary surgical prevention of breast cancer-related lymphedema: over 4 years follow-up. Microsurgery. 2014 Sep;34(6):421-4. doi: 10.1002/micr.22254. Epub 2014 Mar 26.
citation: Torrisi JS, Joseph WJ, Ghanta S, Cuzzone DA, Albano NJ, Savetsky IL, Gardenier JC, Skoracki R, Chang D, Mehrara BJ. Lymphaticovenous bypass decreases pathologic skin changes in upper extremity breast cancer-related lymphedema. Lymphat Res Biol. 2015 Mar;13(1):46-53. doi: 10.1089/lrb.2014.0022. Epub 2014 Dec 18.
citation: Starritt EC, Joseph D, McKinnon JG, Lo SK, de Wilt JH, Thompson JF. Lymphedema after complete axillary node dissection for melanoma: assessment using a new, objective definition. Ann Surg. 2004 Nov;240(5):866-74. doi: 10.1097/01.sla.0000143271.32568.2b.
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citation: Brorson H, Hoijer P. Standardised measurements used to order compression garments can be used to calculate arm volumes to evaluate lymphoedema treatment. J Plast Surg Hand Surg. 2012 Dec;46(6):410-5. doi: 10.3109/2000656X.2012.714785.
citation: Boccardo FM, Casabona F, Friedman D, Puglisi M, De Cian F, Ansaldi F, Campisi C. Surgical prevention of arm lymphedema after breast cancer treatment. Ann Surg Oncol. 2011 Sep;18(9):2500-5. doi: 10.1245/s10434-011-1624-4. Epub 2011 Mar 3.