Reducing chronic breast cancer‐related lymphedema utilizing a program of prospective surveillance with bioimpedance spectroscopy

This single‐institution experience evaluated the use of bioimpedance spectroscopy to facilitate early detection and treatment of breast cancer‐related lymphedema (BCRL) in a cohort of 596 patients (79.6% high risk). Seventy‐three patients (12%) developed an elevated L‐Dex score with axillary lymph node dissection (P < .001), taxane chemotherapy (P = .008), and regional nodal irradiation (P < .001) associated. At last follow‐up, only 18 patients (3%) had unresolved clinically significant BCRL requiring complete decongestive physiotherapy. This rate of BCRL is lower than reported in contemporary studies, supporting recent NCCN guidelines promoting prospective screening, education and intervention for BCRL.


| INTRODUCTION
Breast cancer-related lymphedema (BCRL) represents a sequelae of treatment that can lead to a significant detriment in quality of life. 1 Rates of BCRL following treatment vary widely based on local and systemic therapies utilized with rates as high as 50% noted with more aggressive locoregional therapy, radiation therapy, and taxanebased chemotherapy. 1,2 Therefore, it is imperative to identify patients at high risk for developing symptomatic BCRL so that they can be monitored and receive simple, preemptive intervention, thereby reducing the development of irreversible, chronic BCRL.
Multiple published studies and current guidelines have shown early detection and treatment of subclinical BCRL (using newer techniques and technologies) can prevent progression to its chronic stage, eliminating morbidity and the need for more intensive, costly treatments. [3][4][5][6][7] New techniques, including bioimpedance spectroscopy (BIS) and perometry have been developed to allow for the diagnosis of subclinical BCRL. 8 While a randomized trial evaluating BIS is underway, until the results are published, it is useful to review outcomes in large, single-institution experiences where a structured and consistently applied program of BCRL surveillance using BIS is being employed. Therefore, the purpose of the present analysis was to evaluate outcomes with prospective surveillance in a large number of patients (79.6% high risk) monitored and treated consistently using BIS at a single institution.
Between April 2010 and November 2016, a single institution (Nashville Breast Center, Nashville, TN) enrolled patients in a prospective BCRL surveillance program using the L-Dex U400 Device (ImpediMed, Brisbane, Australia). Patients were followed prospectively using a standard protocol, including upfront BCRL education and a preoperative baseline L-Dex measurement, then postop follow-up measurements. Patients were considered to have an elevated reading if their L-Dex score increased >10 points from baseline (defined as 'subclinical BCRL). 8 Intervention was then triggered and consisted of applying an over-the-counter (OTC) compression sleeve for 4 weeks followed by a recheck of their L-Dex score. The need for complete decongestive physiotherapy (CDP) was defined as Patients were considered high risk (n = 475) if they had an elevated body mass index (BMI, >25) (n = 379), axillary lymph node dissection (ALND) (n = 93), received regional nodal irradiation (RNI) (n = 17), or received taxane chemotherapy (n = 163).
Patients undergoing ALND were more likely to develop an abnormal L-Dex score (31% vs 8%, P < .001) and to have unresolved BCRL (11% vs 1%, P < .001). Median time to first elevated L-Dex score was 4.5 months (range: 0-193) with median time to resolution of 3.8 months from diagnosis (range: 0.1-51.7). Table 2 presents a comparison of patient and treatment characteristics for those patients who developed subclinical BCRL as compared to those that did not.
Those developing subclinical BCRL were less likely to undergo SLNB and more likely to have received adjuvant systemic therapy, taxanebased therapy, and/or RNI. Those developing irreversible, chronic BCRL were less likely to undergo SLNB and more likely to have undergone mastectomy, received adjuvant systemic therapy, taxanebased therapy, high tangents, or RNI.
The results of the current analysis support the concept that prospective surveillance using BIS can detect subclinical BCRL in patients (79.6% of whom were considered high risk), facilitating simple preemptive intervention and resulting in very low rates of chronic BCRL. These results compare favorably to rates of BCRL ranging from 10-50% in multiple large series using conventional surveillance and treatment paradigms. 1,[9][10][11][12] Additionally, the overall lymphedema rate of 3% (persistent L-Dex elevation or clinical BCRL following an OTC sleeve) is lower than reported in modern studies of low-risk patients; the lymphedema rate in over 5000 patients in the ACOSOG Z0010 trial (sentinel node biopsy in T1-2N0 breast cancers) was 7% at only 6 months. 13 Based on these comparisons, the current analysis supports prospective BCRL surveillance in at-risk patients starting with a presurgical L-Dex measurement (with subsequent follow-up measurements and conservative intervention as needed), to help reduce the morbidity associated with BCRL. 1 preoperative baseline is consistent with subclinical BCRL. 8 Bioimpedance spectroscopy has been consistently shown to allow for the subclinical detection of BCRL and just as importantly, evidencebased guidelines are available to provide clinicians with trigger points using L-Dex scores to initiate simple preemptive management. 8,16 An additional component for designing surveillance programs is the need for efficiency with respect to cost, space, and time. Bioimpedance spectroscopy using L-Dex has a minimal space footprint and has been found to add minimal time in its application, allowing for follow-up BCRL assessments at the same time as clinical visits rather than additional follow-ups. 16 As such, with data supporting its utility in prospective surveillance similar to perometry, BIS may be a more attractive option for clinicians due to its minimal space requirements and ease of use. Moving forward, additional data will help quantify the magnitude of improvements in the long-term outcomes of such approaches with respect to chronic BCRL, quality of life, toxicity, and cost.
While prospective surveillance is increasingly being recommended based on randomized and prospective studies, 3,4,6 one concern is iden- It should be noted that all patients that ultimately required CDP were first identified with an elevated L-Dex measurement. In the vast majority of patients with elevated L-Dex scores, BCRL was reversible with a simple OTC compression sleeve applied for 4 weeks. In those that did not respond to this conservative management, it might be that BCRL needs to be detected even sooner in order to prevent progression to its chronic form. Recent data have demonstrated higher sensitivity and specificity of L-Dex when using a 2 standard deviation (SD) trigger, or an L-Dex increase of >6.5 from presurgical baseline rather than the current criterion of 3 SD (L-Dex increase of >10). [18][19][20] This may lead to a higher sensitivity to mild-to-moderate volume changes, something clinicians can use consistently in evaluating their patients for BRCL treatment.
In summary, prospective surveillance of breast cancer patients (most of whom were considered high risk) for the development of