Medical Policy



Subject: Bioimpedance Spectroscopy Devices for the Detection and Management of Lymphedema
Document #: MED.00105 Current Effective Date:    06/28/2017
Status: Reviewed Last Review Date:    05/04/2017

Description/Scope

This document addresses the use of bioimpedance spectroscopy, a device which uses impedance ratios to measure extracellular fluid volume differences between limbs to aid in the clinical assessment of lymphedema.

Note: Please see the following related document for additional information:

Position Statement

Investigational and Not Medically Necessary:

The use of bioimpedance spectroscopy testing in the assessment, diagnosis, or management of individuals with known or suspected lymphedema is considered investigational and not medically necessary.

Rationale

In spite of advances in breast conserving surgical procedures and axillary dissection techniques, breast cancer survivors remain at risk for the development of secondary lymphedema, that is, excessive lymph fluid and protein accumulation in the extracellular space of the affected limb. Studies suggest that 6-40% of breast cancer survivors will develop lymphedema at some point during their lifetime (Ridner, 2009). While conventional clinical methods to diagnose and monitor lymphedema include serial measurements of limb circumference and limb volume (water displacement volumetry), multiple methods of evaluating lymphedema are under study including infrared perometry scanning (infrared light beams image the outline of the limb, which can then be used to calculate limb volume), single and multi-frequency bioelectrical impedance, ultrasound, and lymphoscintigraphy. Some of these studies have included comparisons with conventional measures of lymphedema, such as limb circumference and volume.

Bioelectrical impedance analysis has been studied in research settings for a number of years. In 2008 the United States Food and Drug Administration (FDA) granted 510(k) market clearance for one such device, the ImpediMED L-Dex® U400 BIS Extra Cellular Fluid Analyzer (ImpediMed Limited, San Diego CA). This device is classified as an impedance plethysomograph and was approved for the measurement of extracellular fluid volume differences between the arms to aid in the clinical assessment of unilateral lymphedema of the arm in women. FDA market clearance did not include approval of the device to either diagnose or predict the development of lymphedema of an extremity. In 2011 the FDA granted 510(k) clearance to another Extra Cellular Fluid Analyzer which is manufactured by the same company and lists the L-Dex U400 as the predicate device. The purpose of this submission was to expand the previously cleared indication to include use for legs in women and men and a clarification limiting the device to be used with humans.

Czerniec and colleagues (2010) reported on individuals with lymphedema (n=33) and individuals without lymphedema (n=18) to examine the relationship between physical methods of measuring lymphedema and self-reported swelling. The purpose of the study was to compare the reliability of the most commonly used measures of lymphedema. Measurement techniques included self-report, bioimpedance spectroscopy, truncated cone (circumference) method and infrared perometry. The study concluded that the physical measurement tools studied were reliable with high concordance (0.89 to 0.99) while self-report correlated only moderately with physical measurements (0.65-0.71) and was therefore only moderately reliable. The authors concluded that while lymphedema assessment methods showed good concordance and reliability, they were not interchangeable.

Ridner (2009) reported a feasibility study of single-frequency bioelectrical impedance to detect upper limb lymphedema in non-laboratory settings. Impedance ratios among healthy normal women and breast cancer survivors, both with and without lymphedema were compared. Ratios of healthy normal controls and breast cancer survivor without clinical evidence of lymphedema were similar with nearly complete overlap in confidence intervals. However, those values were markedly different from the values measured in the breast cancer survivor group with lymphedema (p<0.001).

In a 2011 study by Czerniec, the authors sought to determine if bioimpedance spectroscopy could detect lymphedema of the arm and compare the measurements of bioimpedance spectroscopy to that of perometry. With a sample size of 29 women with known lymphedema and 11 women with no history of lymphedema, arm volume was measured by both perometry and bioimpedance spectroscopy. Both techniques were sensitive enough to detect localized lymphedema of the arm and there was a high degree of concordance between the bioimpedance spectroscopy ratio and that determined by perometry. However, sample size was small and larger studies are necessary.

Fu and colleagues (2013) reported on a study which sought to examine the reliability, sensitivity and specificity of bioimpedance spectroscopy in the detection of lymphedema. Circumferential tape measurement was used to validate the presence of lymphedema in 250 women. Bioimpedance was used to measure lymph fluid changes. The 250 women in the study included healthy females, breast cancer survivors with lymphedema, and those who were at risk for developing lymphedema. Bioelectrical impedance analysis, as indicated by L-Dex ratio, for healthy women, was highly reliable (intraclass correlation coefficients [ICC]=0.99) (95% confidence interval [CI] 0.99-0.99), for survivors at-risk for lymphedema (ICC=0.99; 95% CI 0.99-0.99), and all for women (ICC=0.85; 95% CI 0.81-0.87); reliability was acceptable for survivors with lymphedema (ICC=0.69; 95% CI 0.54 to 0.80). The bioimpedance ratio correlated with limb volume by sequential circumferential tape measurement. The L-Dex ratio had a diagnostic cutoff of > +7 which missed 20% of true lymphedema cases. The authors noted that "it is important for clinicians to integrate other assessment methods (such as self-report, clinical observation, or perometry) to ensure the accurate detection of lymphedema."

In a prospective study by Barrio and colleagues (2015), diagnosis of breast cancer-related lymphedema using volume displacement was compared to bioimpedance in 186 participants. All participants received volume displacement and bioimpendance measurements at baseline. The follow-up was for 3 years and measurements were taken at 3- to 6-month intervals. A total of 21 participants had an abnormal bioimpedance measurement, but no lymphedema found by volume displacement, 4 participants had both an abnormal bioimpedance measurement and lymphedema found by volume displacement, and 9 participants developed lymphedema without a prior abnormal bioimpedance measurement. There was no correlation between changes in volume displacement and changes in bioimpedance measurement at 3 months (r=0.31) or 6 months (r=0.21). Of the participants with abnormal bioimpedance measurement, few progressed to lymphedema and those with lymphedema did not have prior abnormal bioimpedance measurements.

The National Comprehensive Cancer Network® NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines® ) in their 2017 guideline for breast cancer recommends that individuals be educated about lymphedema, monitored for lymphedema and referred for management as necessary. However, the guidelines do not address the methods of measurement or monitoring.

Currently, there is insufficient information to judge the technical and diagnostic performance of bioimpedance spectroscopy testing or its clinical utility as studies are limited to small group sizes (Erdogan Iyigun, 2015; Jain, 2010). There is no evidence from comparative clinical trials which demonstrate an impact on clinical outcome. Further study of this technology as a tool for the diagnosis and treatment of early, subclinical lymphedema continues, but based on current evidence, the use of bioimpedance spectroscopy testing in the diagnosis or management of individuals with known or suspected lymphedema is considered investigational.

Background/Overview

Lymphedema is swelling from fluid build-up caused by improper functioning of the lymphatic system. Symptoms of lymphedema include arm swelling, heaviness, chest/breast swelling, tightness, firmness, pain, numbness, stiffness or impaired limb mobility. There are two types of lymphedema: primary lymphedema which occurs in those who have a congenital abnormality or dysfunction of their lymphatic system, and secondary lymphedema which is an acquired condition caused by a disruption or obstruction of the normal lymphatic system. Individuals with breast cancer are at risk for the development of arm lymphedema. Axillary lymph node sampling compromises lymphatic drainage and lymphatic function can be further compromised by radiation delivered to the lymph node beds. Secondary lymphedema can develop days or years after treatment. Most lymphedema occurs within 3 years of surgery and is associated with discomfort, heaviness, functional limitations and risk of infection. Early lymphedema can be difficult to diagnose. Various methods can be used for evaluating limb volume including water displacement, circumferential measurement, infrared perometry and bioelectrical impedance.

Measurement of limb volume with water displacement requires the individual to submerge the affected limb into a cylinder filled with a known volume of water. The amount of water that is displaced can be weighed or the volume measured. Water displacement is a reliable method to measure limb volume, but it can be cumbersome and difficult to perform in the physician's office. It cannot be used for those individuals with open wounds or sores.

Circumferential measurement of limb volume involves the use of a measuring tape to measure limb circumference at various anatomical landmarks or marked distances from the fingertips or toes. A hindrance to circumferential measurement is that individuals must remove the clothing over the affected limb. There is also concern about the reliability of the measurements. Different individuals measuring the limbs may hold the tape measure tightly or loosely around the limb causing a variation in the measurements.

Infrared perometry uses infrared light to measure the limb volume. The affected limb is placed in a frame and the perometer scans the limb taking measurements at different segments. The limb volume is then calculated by a special computer program. Perometry is a quick method and it does not touch the skin so it can be used for individuals with sensitive or broken skin. Clinical application may be limited by the fact that the equipment is not portable and requires individuals to come into a clinic or facility for limb measurement.

Bioelectrical impedance involves the response of a living organism to a mild electrical current. Skin electrodes are used to pass a small alternating current through a limb and measure the opposition (impedance) to the flow of the current. The measure of the body's resistance to the current can be converted into measurements such as fluid levels. Bioimpedance spectroscopy is a direct measurement of extracellular fluid volume. The device is used to detect extracellular fluid in an individual's limb and is being studied as a tool to detect early signs of subclinical lymphedema.

Definitions

Lymphedema: A condition in which extra lymph fluid builds up in tissues and causes swelling. It may occur in an arm or leg if lymph vessels are blocked, damaged, or removed by surgery.

Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services are Investigational and Not Medically Necessary:
When the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

CPT  
93702 Bioimpedance spectroscopy (BIS), extracellular fluid analysis for lymphedema assessment(s)
   
ICD-10 Diagnosis  
  All diagnoses
   
References

Peer Reviewed Publications:

  1. Bar Ad V, Cheville A, Solin LJ, et al. Time course of mild arm lymphedema after breast conservation treatment for early-stage breast cancer. Int J Radiat Oncol Biol Phys. 2010; 76(1):85-90.
  2. Barrio AV, Eaton A, Frazier TG. A prospective validation study of bioimpedance with volume displacement in early-stage breast cancer patients at risk for lymphedema. Ann Surg Oncol. 2015; 22 Suppl 3:370-375.
  3. Czerniec SA, Ward LC, Lee MJ, et al. Segmental measurement of breast cancer-related arm lymphoedema using perometry and bioimpedance spectroscopy. Support Care Cancer. 2011; 19(5):703-710.
  4. Czerniec SA, Ward LC, Refshauge KM, et al. Assessment of breast cancer-related arm lymphedema--comparison of physical measurement methods and self-report. Cancer Invest. 2010; 28(1):54-62.
  5. Erdogan Iyigun Z, Selamoglu D, Alco G, et al. Bioelectrical impedance for detecting and monitoring lymphedema in patients with breast cancer. Preliminary results of the florence nightingale breast study group. Lymphat Res Biol. 2015; 13(1):40-45.
  6. Fu MR, Cleland CM, Guth AA, et al. L-dex ratio in detecting breast cancer-related lymphedema: reliability, sensitivity, and specificity. Lymphology. 2013; 46(2):85-96.
  7. Hayes S, Janda M, Cornish B, et al. Lymphedema secondary to breast cancer: how choice of measure influences diagnosis, prevalence, and identifiable risk factors. Lymphology. 2008; 41(1):18-28.
  8. Jain MS, Danoff JV, Paul SM. Correlation between bioelectrical spectroscopy and perometry in assessment of upper extremity swelling. Lymphology. 2010; 43(2):85-94.
  9. Ridner SH, Dietrich MS, Deng J, et al. Bioelectrical impedance for detecting upper limb lymphedema in nonlaboratory settings. Lymphat Res Biol. 2009; 7(1):11-15.
  10. Stout Gergich NL, Pfalzer LA, McGarvey C, et al. Preoperative assessment enables the early diagnosis and successful treatment of lymphedema. Cancer. 2008; 112(12):2809-2819.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. NCCN Clinical Practice Guidelines in Oncology® . © 2017 National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website: http://www.nccn.org/index.asp. Accessed on April 9, 2017.
    • Breast Cancer (V.2.2017). Revised April 6, 2017.
  2. U.S. Food and Drug Administration 510(k) Premarket Notification Database. ImpediMed L-Dex U400 BIS Extra Cellular Fluid Analysis. No. K080825. Rockville, MD: FDA. October 3, 2008. Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf8/K080825.pdf. Accessed on April 9, 2017.
Websites for Additional Information
  1. National Cancer Institute (NCI). Available at: http://www.cancer.gov/. Accessed on April 9, 2017.
Index

L-DexU400
Lymphedema

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

Document History

Status

Date

Action

Reviewed 05/04/2017 Medical Policy & Technology Assessment Committee (MPTAC) review
Reviewed 05/03/2017 Hematology/Oncology Subcommittee Review. Updated Rationale and References sections.
Reviewed 05/05/2016 MPTAC review.
Reviewed 05/04/2016 Hematology/Oncology Subcommittee Review. Updated Rationale and References sections. Removed ICD-9 codes from Coding section.
Reviewed 05/07/2015 MPTAC review.
Reviewed 05/06/2015 Hematology/Oncology Subcommittee Review. Updated Rationale and References.
  01/01/2015 Updated Coding section with 01/01/2015 CPT changes; removed code 0239T deleted 12/31/2014.
Reviewed 05/15/2014 MPTAC review.
Reviewed 05/14/2014 Hematology/Oncology Subcommittee Review. Updated Rationale and References.
Reviewed 05/09/2013 MPTAC review.
Reviewed 05/08/2013 Hematology/Oncology Subcommittee Review. No change to Position Statement.
Revised 05/10/2012 MPTAC review.
Revised 05/09/2012 Hematology/Oncology Subcommittee Review. Clarification to Position Statement. Updated Rationale, Background/Overview, and References.
Reviewed 08/18/2011 MPTAC review. Updated Rationale and References.
New 08/19/2010 MPTAC review. Initial document development. Coding section includes CPT changes effective 01/01/2011.