Detection Of Breast Cancer-related Lymphedema Research Articles

Abstract PO3-12-07: Utility of Volumetric Measurement for Clinical Diagnosis of Breast Cancer-Related Lymphedema

Abstract Background: Early detection of Breast cancer-related lymphedema (BCRL) is crucial since it can significantly reduce the negative impact on a patient’s quality of life after breast cancer treatment. Several objective screening methods have been used in prior studies but have not proven accurate due to a lack of standardization. Bioimpedance spectroscopy (BIS), which assesses tissue resistance to an electric current and converts it into a score to measure interstitial fluid content, has proven to be an accurate tool in diagnosing lymphedema. SOZO® is a BIS device that generates quantitative results in real time and provides a Lymphedema Index (L-Dex) score by measuring the patient's extracellular fluid volume. However, there is a paucity of literature highlighting its clinical applicability. Thus, we aimed to evaluate the clinical utility of SOZO® in diagnosing BCRL in patients undergoing breast cancer surgery. Materials & Methods: A retrospective chart review was carried out of patients who underwent axillary surgery from January 2019 to December 2022. Demographic information such as age, body mass index (BMI), gender, ethnicity, disease pathology, cancer stage, type of axillary surgery, neoadjuvant and adjuvant treatment received was recorded. Patients undergoing sentinel lymph node biopsy (SLNB) and/or axillary lymph node dissection (ALND) were assessed for their preoperative L-Dex score, and they were followed up postoperatively with repeated measurements of their L-Dex score to diagnose lymphedema for a year at 3 months intervals. Clinical lymphedema was defined as those having an absolute L-Dex score of more than +10 and an increase in L-Dex score by 6.5 from the baseline. SOZO® scores measured at each follow-up were compared to their preoperative baseline scores. Results: A total of 200 patients’ data was evaluated whose mean age and BMI were 57.5+10.9 years and 29.6+5.6 kg/m2, respectively. Eighty-five percent of the patients belonged to ethnic minority groups. Furthermore, 84.5% (n=169) of the patients had SLNB, and 15.5% (n=31) had ALND. All the patients included in the study had their preoperative and postoperative quarterly L-Dex scores recorded. Pre- and post-operative L-Dex scores had a mean of -0.20+6.6 and 0.61+6.8, respectively. A total of 20 (10%) patients developed lymphedema without symptoms detected by SOZO®, with 19 (9.5%) resolving at their respective 3-month follow-up and 1 (0.5%) patient with persistent lymphedema at the end of the 24-month follow-up. All 20 patients were treated with a compression sleeve. Of the 20 patients with lymphedema, 4 patients underwent ALND, whereas 16 patients had SLNB. When compared to their preoperative baseline scores, all patients' SOZO® measurements had an absolute score of more than 10 and an increase of 6.5 from their baseline score. Additionally, 21 other patients had an increase in score of 6.5 from their baseline measurements but did not meet the cut-off range of an absolute score of +10. Therefore, we excluded them from the diagnosis of BCRL, and none of these patients later developed any signs of BCRL, such as swelling, pain, or discomfort. Conclusion: SOZO® procedure can accurately detect BCRL. In our study, 1 patient developed clinical lymphedema after undergoing SLNB and was diagnosed using SOZO®. Additionally, 19 patients who were initially diagnosed with lymphedema were later categorized as transient due to the resolution of lymphedema on follow-up. Early identification of transient lymphedema using SOZO® resulted in the prevention of a potentially life-long debilitation in our patients. Moreover, our findings underscore that an increase in SOZO® score from the baseline by > 6.5 with an absolute score of more than +10 should be the threshold to clinically diagnose lymphedema. Future studies with larger sample sizes and longer follow-up duration are necessary to understand better the utility of SOZO® in diagnosing BCRL. Table 1: Baseline characteristics and follow-up data of the patients included in the study. Citation Format: Fardeen Bhimani, Sheldon Feldman, Yu Chen, Anjuli Gupta, Jessica Pastoriza, Areej Shihabi, Maureen McEvoy. Utility of Volumetric Measurement for Clinical Diagnosis of Breast Cancer-Related Lymphedema [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-12-07.

Early Detection of Breast Cancer-Related Lymphedema: Accuracy of Indocyanine Green Lymphography Compared with Bioimpedance Spectroscopy and Subclinical Lymphedema Symptoms.

Introduction: The reported incidences of breast cancer-related lymphedema (LE) affecting the arms vary greatly. Reason for this variability includes different diagnostic techniques used across studies. In the current study, we compared the accuracy of indocyanine green lymphography (ICG_L) and bioimpedance spectroscopy (BIS) in detecting LE before presentation of clinical signs. Methods and Results: Patients with no initial detectable signs of clinical LE of their arms after axillary lymph node dissection or removal of >5 lymph nodes on sentinel lymph node biopsy were included. Subclinical LE was defined as BIS values outside the normal range [(≥7 units (or >10 units)] or a 7-unit (or 10 unit) change between two measurements. We tracked ICG_L and BIS measurements for 133 potentially affected arms (n = 123). ICG_L detected signs of lymphatic flow disruption in 63 arms (47%). Based on the BIS value of 7 units, 60 arms (45%) had values outside the normal range. When using ICG_L-identified LE cases as true positives, BIS had a 54% accuracy (area under the curve [AUC] = 0.54) in detecting LE. Accuracy was 61% for subclinical LE symptoms when compared with ICG_L (AUC = 0.62). Both BIS and subclinical LE symptoms had <0.70 AUC-receiver characteristic operator curve, suggesting that BIS and development of subclinical LE symptoms are not adequate for identifying patients with subclinical LE. Conclusion: ICG_L is a reliable diagnostic tool for detecting early signs of lymphatic flow disruption in subclinical LE. Utilizing ICG_L to diagnose subclinical LE followed by a personalized treatment plan may provide patients the best chance of preventing disease progression.

Early Detection of Breast Cancer-Related Lymphedema in COVID-19 Pandemic.

Background: This study aimed at presenting a prospective surveillance model of care delivered at home for women qualified for surgery due to breast cancer under the epidemic-related restrictions. Methods and Results: Women (age ≥18 years, diagnosed with breast cancer, no clinical features of upper limbs lymphedema, and a volume difference between the limbs <5%, not using any prophylactic compression products) will be provided with comprehensive education in the field of self-measurements and lymphedema prevention. The outcome measures include limb volume (circumferential measurements with a tape at 4 cm intervals), simplified protocol of three measurement points combined with the symptoms monitoring (according to the physical section of Lymphedema Quality of Life Inventory [LyQLI]). We propose a new calculation method as the RACI (relative arm circumference increase) in accordance with previous research-RAVI (relative arm volume increase) and the new proposal-the RACD (relative arm circumference difference). According to cylinder formula it can be calculated that 5% increase in limb volume results in ∼2% change in RACI. Regular appointments will be planned at 3, 6, 9, and 12 months after the enrollment. Additional urgent appointments will be arranged after the home or phone "red flags" (an increase circumference by ≥2%, positive pitting test, and any new symptoms) detection. We hypothesize that performing only three measurements combined with the typical symptoms monitoring would be accurate for lymphedema diagnosis based on the RAVI of ≥5%. Moreover, RACI/RACD increments combined with positive symptoms would correlate with RAVI. Conclusions: The new proposal of protocol can be the optimal solution in COVID-19 pandemic.

Determination of Bioelectrical Impedance Thresholds for Early Detection of Breast Cancer-related Lymphedema.

Background: Bioelectrical impedance technology is a common technique used for the early detection of breast cancer-related lymphedema (BCRL). However, studies on the threshold value established by Inbody 720 device (Biospace, Korea) have been extremely limited. We aimed to determine its reference range and cutoff values.Methods: All patients were recruited from October 2017 to October 2019 at the Peking University People's Hospital Breast Center. In total, 82 patients with unilateral BCRL and 1305 healthy subjects were recruited in this study. We measured the extracellular fluid (ECF) ratio, extracellular water (ECW) ratio, as well as the single-frequency bioimpedance analysis (SFBIA) ratios at 1 and 5 kHz with the Inbody 720 device. The Youden index-based cutoff points, mean + 2SD and mean + 3SD values of these four indicators for both dominant and nondominant arms were also calculated.Results: Data were collected from 1387 women, including healthy subjects and patients with lymphedema. All statistical analyses were performed with SPSS. Significant differences were found between the two groups in the ECW, ECF, and SFBIA ratios. For the dominant affected arms, the Youden index-based cutoff points for the ECF, ECW, as well as SFBIA ratios at 1 and 5 kHz were 1.009, 1.008, 1.068, and 1.068, respectively. For the nondominant affected arms, the Youden index-based cutoff points were 1.014, 1.013, 1.047, and 1.048, respectively. The mean + 2 standard deviations (SD) and mean + 3SD values were also calculated.Conclusions: We determined the Youden index-based cutoff points, mean + 2SD and mean + 3SD values of the ECF, ECW, as well as SFBIA ratios at 1 and 5 kHz for both dominant and nondominant arms with data from 1305 healthy subjects. Next, the Youden index-based cutoff points, the mean + 2SD and mean + 3SD values were used to recognize patients with lymphedema. We found that the Youden index-based cutoff points and the mean + 2SD showed similar identification capacity on lymphedema, and they seemed to distinguish more patients with lymphedema than mean + 3SD values.

Three Decades of Bioelectrical Impedance Spectroscopy in Lymphedema Assessment: An Historical Perspective.

Bioelectrical impedance spectroscopy (BIS) is a technology that is widely used for the assessment of body composition. The method is based on the measurement of the electrical resistance of the body or a body region that can be quantitatively related to the amount of water in the tissues. Lymphedema is characterized, at least in its early stages, as an accumulation of lymph, an extracellular fluid. In the late 1980s, it was recognized that it might be possible to adapt BIS protocols to measure this increase in lymph volume. Subsequently, the use of BIS for the early detection of breast cancer-related lymphedema was demonstrated in the early 1990s, with BIS reference values indicative of lymphedema published in 2001. The subsequent two decades have seen BIS become a widely accepted method for lymphedema assessment. This review traces the evolution of the BIS technique since its inception and presents the current state of the art, with particular emphasis on utility in clinical practice.

Interchangeability of Two Electrode Placement Protocols Used by Bioimpedance Spectroscopy Devices in the Detection of Breast Cancer-Related Lymphedema.

Background: Bioimpedance spectroscopy (BIS) devices are routinely used in the assessment of breast cancer-related lymphedema (BCRL). The equipotential electrode placement is a commonly used protocol for the assessment of BCRL. However, the sternal notch electrode placement protocol is also in use. Whether these two protocols are interchangeable is not known. Methods and Results: Ethical approval was received from the institutional ethics committee at Tata Memorial Hospital, India. BIS measurements (whole-body right side and affected and unaffected arms) of 100 women with or at risk of BCRL were measured using equipotential and sternal notch protocols. Resistance at zero frequency (R0) was determined, and agreement of the absolute R0 values and the R0 ratio (unaffected/affected) between protocols was evaluated (Bland-Altman analysis and Passing-Bablok regression analysis). Mean absolute differences between protocols were very small for whole-body right side, affected arm, unaffected arm, and the interarm ratio at 0.23 ohms (95% confidence interval [CI]: -3.8 to 4.3), -5.7 ohms (95% CI: -7.5 to -3.9), -9.09 ohms (95% CI: -11.4 to -6.8), and -0.008 ohms (95% CI: -0.02 to 0.001), respectively. Limits of agreement (two standard deviation) between protocols were narrow for whole-body right side, affected arm, unaffected arm, and interarm ratio without any systematic or proportional differences for whole-body right side and the interarm ratio (5.8% to -5.6%, 3.7% to -7.4%, 3.5% to -8.2%, and 5.8% to -5.6%, respectively). Conclusion: The equipotential and sternal notch protocols could be used interchangeably in BCRL assessment. The Clinical Trial Registration number: CTRI/2017/12/010762.

A Prospective Study of L-Dex Values in Breast Cancer Patients Pretreatment and Through 12 Months Postoperatively

Data regarding pretreatment, bioimpedance spectroscopy (BIS) L-Dex® values for patients newly diagnosed with breast cancer, and longitudinal data 12 months postoperatively are lacking. This study describes L-Dex values at the time of breast cancer diagnosis and maximum L-Dex change within 12 months of surgery. Patients were enrolled in a parent, clinical trial that compares the effectiveness of BIS for early detection of breast cancer-related lymphedema to tape measurement. A total of 280 women with a pretreatment and at least one postoperative L-Dex measurement (within 12 months of surgery) were included. Pretreatment L-Dex readings were compared with population norms and maximum L-Dex changes within 12 months were examined. An L-Dex U400 device was used to obtain BIS measurements. The documented normative mean value using this device is 0.00, which is at the 49th percentile for this sample. Approximately 6% of patients had a pretreatment L-Dex value of ≥7.0; 1.8% had an L-Dex value ≥10.0. For 12 months, 17.1% (n = 48) of patients had a maximum change in L-Dex value from pretreatment of ≥7.0 L-Dex units, suggestive of clinical lymphedema. At the time of breast cancer diagnosis, L-Dex values are similar to normative values. Identified maximum changes in L-Dex values 12 months postoperatively suggest that frequent L-Dex measurements during that time frame are of potential clinical benefit. Our findings are consistent with research supporting an L-Dex value of ≥7 as indicative of clinical lymphedema with subclinical lymphedema logically occurring at somewhat lower likely, near ≥6.5.

Perometry versus simulated circumferential tape measurement for the detection of breast cancer-related lymphedema.

Despite increasing emphasis on screening and early intervention for breast cancer-related lymphedema (BCRL), there is marked heterogeneity in diagnostic methodology, including for volumetric measures. This retrospective study compared two volumetric modalities, perometry and simulated circumferential tape measurement (anatomic- and interval-based), for BCRL detection. Between 2005 and 2017, 287 female patients with unilateral breast cancer were prospectively screened for BCRL by perometry and the relative volume change (RVC) formula. Circumferential measurement was performed by sampling at five anatomic landmark-based points or 4-cm intervals from pairs of perometerarm diameter measurements. Volumetric conversion was by a frustum model. The Bland-Altman method was used to compare segmental volume differences. Confusion matrix analysis was performed for each circumferential measurement technique against perometry. Median follow-up was 34.7months over4 postoperative visits. There was no difference in total arm volume comparing any of the circumferential measurementtechniques to perometry. Landmark-based methods significantly underestimated upper arm volume (mean difference - 207mL [- 336, - 78 mL]) and overestimated forearm volume (mean difference + 170mL [+ 105, + 237mL]). Landmark-based methods had greater sensitivity and specificity compared to 4-cm interval methods for detection of both RVC ≥ 10 and 5-10%. Landmark-based methods were comparable to perometry for detection of RVC ≥ 10%, but sensitivity was only 63.2-66.7% for RVC 5-10%. This hypothesis-generating study suggested the superiority of anatomic landmark-based circumferential tape measurement compared to interval-based methods, while generating questions about the underestimation of upper arm volume and overestimation of forearm volume of circumferential tape measurement compared to perometry.

Early Assessment for Prevention of Breast Cancer–Related Lymphedema

Abstract Breast cancer–related lymphedema (BCRL) is an incurable, disfiguring, progressive complication occurring after breast cancer treatment. BCRL is difficult to treat and is characterized by significant and persistent swelling. Lymphedema is the most common morbidity resulting from breast cancer treatment. Therefore, BCRL should be assessed during clinic visits in oncology and primary care settings. An evidence-based algorithm for early detection of BCRL in primary care settings is presented with explanations of the protocol elements.

Abstract OT3-07-01: A randomized trial evaluating bioimpedance spectroscopy vs. tape measurement in the prevention of lymphedema following breast cancer treatment

Abstract Background: Breast cancer related lymphedema (BCRL) represents a common treatment associated complication following surgery, radiation and/or chemotherapy. Increasing data has demonstrated the ability of new diagnostic modalities to detect BCRL in the subclinical phase of the process allowing for early intervention. Trial Design: This 2-group stratified randomized clinical trial evaluates the effectiveness of bioimpedance spectroscopy (BIS) for early detection and prevention of BCRL compared to tape measurement (TM). Baseline assessments are made pre-operatively. Two-months post-op, patients are censored out if they have developed any of the exclusion conditions, did not have a mastectomy, axillary dissection, &amp;gt;6 sentinel nodes removed, radiation therapy, or taxane. Remaining patients are randomized within site to either BIS or TM; monitored at 3 to 6-month intervals up to 36-months post-op for a change over baseline specified to trigger a compression sleeve &amp; gauntlet intervention. Cohort trigger thresholds are change of ≥10 L-Dex units or 5 to &amp;lt;10% volume. If the intervention is triggered, measurements by the other method are taken before initiating the 4-week intervention. Post intervention, patients are monitored only with TM. Volume change of ≥10% results in study removal and physician referral. At the 2 study endpoints (36 month visit or volume change of ≥10%) measurements are taken with each method. Eligibility Criteria: Inclusion criteria: ≥ 18 with histologically confirmed stage I-III breast cancer (BC) or DCIS with planned surgery. Exclusion criteria include history of BC therapy or lymphedema. Specific Aims: The primary hypothesis is that subclinical detection of BCRL with BIS and early intervention will reduce the rate of lymphedema progression (as measured by referral to complex decongestive physiotherapy) compared to TM. Secondary outcomes include BCRL risk factors, quality of life, and time to treatment. Statistical Methods: Sample size and powering were based on the hypothesis that BIS would reduce progression rate by 20%. A rate of 50% progression in the TM group was used as the standard. 1100 patients will be enrolled to result in randomized groups of 100 (Total N=200) Statistics include relative risks with respective bootstrapped 95% C.I. and Cochran-Mantel-Haenszel tests. Present Accrual and Target Accrual: Overall, the study target or expected enrollment as of the end of March 31, 2016 was 690 participants, 534 were actually enrolled (actual accrual 77% of target). Accrual at the study sites ranged from 15 to 104% of target. Contact Information: Sheila Ridner: 615-322-0831, Sheila.ridner@vanderbilt.edu Support: ImpediMed Limited, ImpediMed, Inc. and medi USA. Citation Format: Ridner S, Shah C, Dietrich M, Vicini F. A randomized trial evaluating bioimpedance spectroscopy vs. tape measurement in the prevention of lymphedema following breast cancer treatment [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT3-07-01.

Proactive approach to risk reduction and early detection of breast cancer-related lymphedema.

95 Background: Advances in surgery and post-operative treatment continue to reduce the incidence of late effects of cancer treatment such as lymphedema. Yet, many breast cancer survivors still face considerable post-operative challenges as a result of developing lymphedema. The purpose of this study was to preliminarily evaluate an educational and behavioral program “The Optimal YOU” to enhance lymphedema risk reduction among patients with breast cancer. The intervention focuses on preventing inflammation-infection, promoting lymph drainage, and maintaining optimal BMI as well as preoperative and subsequent follow-up assessment of limb volume changes and symptoms. Methods: A quasi-experimental design with repeated-measures was used to assess outcomes of The Optimal YOU program at pre-operative baseline, post-operative, 6-month, and 12-month follow-up. A total of 147 patients newly diagnosed with breast cancer were recruited and received the program. The program outcome data include lymph volume changes by infra-red perometer-S350, lymphedema-related symptoms by Lymphedema Symptom Experience Index, and body mass index (BMI) by Bioimpedance DF50. Results: Among the 147 patients, 141 patients completed the study (4% attrition rate). Majority (94%) of patients maintained preoperative limb volume and improved their symptom experience at 12-month follow-up. During the 12-month study period, only five patients (6%) developed lymphedema and were referred for lymphedema treatment. At 12-month follow-up, among the five patients who developed measurable lymphedema, two patients’ limb volume returned to pre-operative level without compression therapy only by maintaining exercises of The Optimal YOU to promote daily lymph flow. About 80% of patients maintained or improved their preoperative BMI. Conclusions: The study shows that proactive approach to implementing The Optimal YOU program is effective to risk reduction and early detection of breast cancer-related lymphedema by focusing on preventing inflammation-infection, promoting lymph drainage, and maintaining optimal BMI.