- 2017 - Pilot Grant
Lymphedema affects 140 million people worldwide and 3 million patients suffer from this disease in the United States alone. An important sub-population is patients with breast cancer related lymphedema (BCRL), which affects over 400,000 patients in the United States. Symptoms include fatigue, tightness, pain, and the potential of life threatening infections. Lymphedema is associated with a diminished quality of life (QOL) and BCRL patients incur twice the cost in medical expenses as breast cancer survivors who do not develop lymphedema.1 Physical therapy, the gold standard treatment, offers marginal relief. At Beth Israel Deaconess Medical Center (BIDMC), we offer surgical therapies for lymphedema including lymph node transfer and lymphovenous bypass. While these interventions alleviate symptoms and improve QOL, they do not provide a definitive cure and a large proportion of patients are not surgical candidates. Morbidity from lymphedema remains significant and there is an unmet need to rigorously explore alternative therapies.
While early data has demonstrated the benefits of acupuncture for BCRL2-8, the mechanism of action is poorly understood. Lymphedema is a progressive disorder that is initiated by inflammation and progresses to fibrosis. Moreover, as inflammation progresses in one region of the body, a systemic alteration in lymphatic function has been observed but is also poorly understood. Current avenues of basic science research are geared towards localizing molecular targets for inflammation9,10 and/or fibrosis11-13 in order to potentially prevent and/or treat lymphedema.
The goal of this proposal is to demonstrate the feasibility and preliminary efficacy of acupuncture for BCRL while beginning to explore the mechanistic underpinnings of this treatment. Specifically, we will conduct a single-arm proof-of-concept pilot study offering patients (N=20) with unilateral BCRL a 6-week acupuncture intervention with unprecedented rigorous monitoring of the affected upper extremity and the systemic response.
(1) Evaluate the feasibility [patient enrollment > 80%, completion of 9 acupuncture sessions, and ≥75% of patients completing all 3 testing visits] of executing a rigorous monitoring system of both the systemic and local response to lymphedema following acupuncture therapy.
(2) Determine preliminary efficacy of treatment from local (circumferential measurements, bioimpedance spectroscopy, perometry, and durometry), systemic (IL4, IL10, TNFb), and patient centered perspectives (LYMQOL, a quality of life measure for limb lymphedema14).
We hypothesize that the beneficial effect of acupuncture in BCRL patients is achieved through a reduction in the extracellular fluid in the affected extremity. We further conjecture that this change in fluid volume is related to changes in the systemic inflammatory response, and that this will also result in improvements in symptoms and quality of life.
Our innovation arises from the unprecedented battery of testing available at the BIDMC Lymphedema Clinic which will allow us to better elucidate the potential mechanism of action acupuncture has on lymphedema. Specifically, our institution supports 2 certified lymphedema therapists who have been provided with the state of the art lymphedema monitoring equipment. We maintain a rigorous methodology of long board extremity measurements allowing for measurements every 4cm and algorithmic volume calculation with the truncated cone formula. We utilize bioimpedance spectroscopy as a routine method of assessing changes in extracellular fluid. We monitor changes in extremity volume utilizing perometry. Finally, an IRB approved experimental durometer is utilized to assess subtle skin changes in lymphedema patients. All of our patients are also monitored for patient centered outcomes utilizing the LYMQOL. The above objective measures are monitored prospectively in our IRB approved REDcap15 BIDMC Lymphedema Repository. Finally, our institution has a core laboratory dedicated to evaluation of inflammatory markers which will allow us to begin exploring the mechanistic underpinnings of the affect of acupuncture on lymphedema.
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