CLUE tool emerges as reliable and valid tool to assess breast cancer-related lymphedema severity

Oct. 04, 2019

Breast cancer-related lymphedema (BCRL) is an abnormal accumulation of protein-rich interstitial fluid that can accumulate in the upper extremity, breast and torso. BCRL is often a consequence of cancer treatment, when portions of the lymphatic system become injured during surgical resection or radiation. Left untreated, BCRL may progress and lead to infections, hospitalizations, increased health care costs and reduced quality of life.

Currently available methods to measure upper extremity lymphedema include bioimpedance spectroscopy (BIS), limb size measurements (including water displacement, circumferential tape measurements and perometry) and self-report. All of these methods have strengths and limitations in their capacity to diagnose and assess BCRL.

The Cancer-Related Lymphedema of the Upper Extremity (CLUE) tool is a relatively new, standardized clinical and physical assessment tool for lymphedema. It is designed for use by health care professionals who care for patients with a history of breast cancer. This tool uses the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, as well as clinically relevant BCRL domains identified by lymphedema experts and reinforced through consensus processes among investigators.

The need to accurately evaluate the efficacy of prevention and treatment strategies for BCRL prompted a team of researchers to study the reliability of the CLUE tool as a means to formally grade or measure the severity of lymphedema. The results of this study were published in the Archives of Physical Medicine and Rehabilitation in 2019.

"Developing a standardized physical assessment for BCRL that is reliable and valid could help us establish a common clinical standard and a uniform single score for use when estimating treatment efficacy in clinical trials," explains Andrea L. Cheville, M.D., a co-author on the Archives of Physical Medicine and Rehabilitation article and a physiatrist and researcher at Mayo Clinic's campus in Rochester, Minnesota. "The purpose of this study was to determine the intra- and interrater reliability and concurrent validity of the newly developed CLUE tool."


The researchers designed and conducted a blinded repeated-measures observational study that involved 71 women with and without lymphedema who are breast cancer survivors (between ages 31 and 81) and were recruited between 2014 and 2015.

Researchers recorded measures of lymphedema symptom severity performed in two rounds of assessment using the following methods:

  • Perometric measurements
  • Norman lymphedema survey responses
  • CLUE tool scores, including visual assessment of obscuration of anatomical architecture, assessment of deviation from normal anatomical contour, tissue texture assessment, and pitting or nonpitting edema assessment

Assessments were completed independently by two highly experienced, certified lymphedema therapists (rater 1 and rater 2). During the first assessment, participants completed the Norman lymphedema survey and perometry, and they underwent all of the physical assessments included in the CLUE tool. Participants were classified as having stage 0, 1, 2 or 3 lymphedema according to CTCAE by rater 1. The participants then returned within 21 days for a second assessment performed by the same rater. Raters were blinded to assessments performed by other raters and to participant responses on the Norman lymphedema survey.

Results and conclusions

According to Dr. Cheville and colleagues, the study results indicate that the CLUE tool demonstrated excellent overall inter- and intrarater reliability. Additionally, the overall CLUE score for the upper extremity demonstrated moderately strong concurrent validity when applying both objective and subjective measures.

"The CLUE tool appears to be a reliable and valid clinical assessment tool that adds minimal administrative burden. It also provides clinicians and researchers with a standardized clinical assessment of BCRL and a single score that captures the multidimensionality of lymphedema," says Dr. Cheville. "Future research should strive to determine whether the CLUE tool can also detect subclinical and or new-onset lymphedema and sensitivity to change."

For more information

Spinelli B, et al. Intra- and interrater reliability and concurrent validity of a new tool for assessment of breast cancer-related lymphedema of the upper extremity. Archives of Physical Medicine and Rehabilitation. 2019;100:315.