Despite advances in breast-conserving surgery, improved radiation protocols, the advent of certain biopsies, and chemotherapy regimens, breast cancer-related lymphedema remains a major source of morbidity and concern among breast cancer patients. Up to 30 percent of women treated for breast cancer develop lymphedema in one or both arms after surgery, radiation therapy, or chemotherapy. The traditional method for evaluating a patient's risk of developing lymphedema is to measure the circumference of the arm with a tape measure, but increasingly, studies have shown that this does not provide the most accurate or timely assessment of lymphedema progression.
Like many medical conditions, secondary cancer-related lymphedema develops in stages and, if caught early, progression can be prevented (Figure 1). At stage 0, lymphedema is reversible. The lymphatic system is impaired but there is not enough fluid buildup for patients to notice symptoms.
At stage I, fluid accumulation usually results in noticeable swelling and discomfort. Treatment at this stage can alleviate symptoms and sometimes reverse progression. At stages II and III, lymphedema is irreversible.
Unfortunately, the majority of cases are not diagnosed until they are already visually apparent. If changes could be found before they are visually apparent, patients could receive treatment that could prevent the condition from getting worse (Ann Surg Oncol 2018; http://doi.org/10.1245/s10434-018-6601-8).
Lymphedema Prevention
Interim clinical results from the PREVENT trial demonstrate that lymphedema could be preventable if caught at its earliest stages, before a patient experiences symptoms and begins treatment with at-home care, including appropriate compression garments. The PREVENT Trial employs bioimpedance spectroscopy (BIS) technology, which measures impedance at 256 different frequencies over a full spectrum (from 3 kHz to 1,000 kHz) and does not depend upon population-specific prediction equations to generate fluid volumes or tissue masses. Because the technique used does not assume that extracellular fluid (ECF) and intracellular fluid (ICF) are uniformly distributed, it provides a more direct and individualized measure of ECF, ICF, and total body water compartments of the body, creating significant advantages, particularly in patient populations with altered fluid homeostasis.
The PREVENT Trial is the largest, multi-site randomized controlled trial ever performed to study lymphedema prevention. The pre-specified interim analysis followed the first 508 patients enrolled in the study through 12 months of follow-up. Surveillance of women at risk for breast cancer-related lymphedema using BIS to identify early changes in ECF, when combined with immediate compression therapy, resulted in 95 percent of those women not experiencing lymphedema progression. These interim clinical results demonstrate that lymphedema is largely preventable if caught early and if treated at home using appropriate compression garments.
To catch lymphedema at stage 0 or stage I, at-risk patients must be routinely monitored during clinical assessments using BIS, which measures their L-Dex score. This score measures the fluid accumulation in a limb that is at risk for lymphedema and compares it to a healthy limb. An increase in the L-Dex score of 6.5 from a baseline value is an indicator of the development of lymphedema and, combined with clinical assessment, triggers the need for at-home intervention using compression garments (Figure 2) (Ann Surg Oncol 2019; https://doi.org/10.1245/s10434-019-07344-5). At this stage, off-the-shelf compression sleeves, which are less expensive than custom garments (often required for chronic lymphedema), are typically required for 4 weeks.
L-Dex Score History Chart
With early detection, cancer survivors can avoid facing the common symptoms of lymphedema, such as swelling, mobility issues, and hospitalization for potentially fatal infections, as well as time-consuming daily care regimens and purchasing expensive compression garments.
Results from other studies have also demonstrated that prospective monitoring utilizing the L-Dex score combined with early intervention for breast cancer patients at risk for lymphedema lowered progression to chronic lymphedema. These findings support early prospective screening and intervention for cancer patients at risk of developing lymphedema.
BIS vs. Tape Measure
The BIS device is a direct measure of extracellular fluid, whereas the tape measure simply measures the overall volume of the arm. Tape measure does not differentiate between volume gain due to fluid, muscle, or fat. BIS is sensitive to changes in lymphatic fluid, shown to detect as little as 2.4 tablespoons (36 m) of fluid differences between the arms. Although tape measurement is the most commonly used lymphedema measurement method around the world, accuracy of measurement is problematic. In starting the PREVENT Trial at multiple sites, we provided an initial half day of training in order to get accurate tape measurements for the research study and we conduct yearly fidelity visits to make sure there has been no slippage in techniques.
The PREVENT Trial interim results demonstrate that surveillance of breast cancer survivors using L-Dex should be routinely used in clinical practice and coupled with a conservative compression intervention to prevent lymphedema (Ann Surg Oncol 2019; https://doi.org/10.1245/s10434-019-07344-5).