Early Detection and Treatment
Implementation/Feasibility
Diagnostic Comparison
Validation Studies
Guidelines
Economics/Quality of Life
Pathophysiology
Review Articles
Editorials
Early Detection and Treatment

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Open Access

1 Reducing Breast Cancer-Related Lymphedema (BCRL) Through Prospective Surveillance Monitoring Using Bioimpedance Spectroscopy (BIS) and Patient Directed Self-Interventions. Kilgore, L.J., et al., Reducing Breast Cancer-Related Lymphedema (BCRL) Through Prospective Surveillance Monitoring Using Bioimpedance Spectroscopy (BIS) and Patient Directed Self-Interventions. Ann Surg Oncol, 2018 Kilgore, L.J., et al. Our results demonstrated that early conservative intervention for breast cancer patients high risk for BCRL who were prospectively monitored by utilizing BIS significantly lowers rates of BCRL. These findings support early prospective screening and intervention for BCRL.
Early detection with patient-directed interventions improves patient outcomes and decreases the risk of persistent BCRL.
Link to paper No
2 A Prospective Study of L-Dex Values in Breast Cancer Patients Pretreatment and Through 12 Months Postoperatively. Ridner, S.H., et al., A Prospective Study of L-Dex Values in Breast Cancer Patients Pretreatment and Through 12 Months Postoperatively. Lymphat Res Biol, 2018. 16(5): p. 435-441 Ridner, S.H., et al. 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. Link to paper No
3 Reducing chronic breast cancer-related lymphedema utilizing a program of prospective surveillance with bioimpedance spectroscopy. Whitworth, P.W. and A. Cooper, Reducing chronic breast cancer-related lymphedema utilizing a program of prospective surveillance with bioimpedance spectroscopy. Breast J, 2018. 24(1): p. 62-65 Whitworth, P.W. and A. Cooper In summary, prospective surveillance of breast cancer patients (most of whom were considered high risk) for the development of BCRL using BIS permitted the detection and simple pre-emptive management of subclinical disease resulting in a very low rate of chronic lymphedema compared to the established, expected range. These findings (which represent the largest group of patients monitored in a structured, program for early detection of BCRL using BIS) support the cost-effective allocation of resources for prospective, BIS assisted, BCRL surveillance within guidelines-based breast cancer survivorship programs. For women at risk for BCRL, this protocol represents a useful option to meet NCCN guidelines for the education, monitoring and treatment of BCRL. Link to paper Yes
4 Preventing Breast Cancer-Related Lymphedema in High-Risk Patients: The Impact of a Structured Surveillance Protocol Using Bioimpedance Spectroscopy. Whitworth, P.W., et al., Preventing Breast Cancer-Related Lymphedema in High-Risk Patients: The Impact of a Structured Surveillance Protocol Using Bioimpedance Spectroscopy. Front Oncol, 2018. 8: p. 197 Whitworth, P.W. et al. The results of this analysis underscore previously published data on the efficacy of prospective BCRL surveillance and early intervention using BIS. Of the 93 high-risk patients prospectively followed and managed in this structured BCRL protocol, only 11% required CDP and only 3% required continued therapy. These excellent outcomes are superior to contemporary studies of conventional measures reporting BCRL rates in similarly treated high-risk patients. Link to paper Yes
5 Utilization of bioimpedance spectroscopy in the prevention of chronic breast cancer-related lymphedema. Kaufman, D.I., et al., Utilization of bioimpedance spectroscopy in the prevention of chronic breast cancer-related lymphedema. Breast Cancer Res Treat, 2017. 166(3): p. 809-815 Kaufman, D.I., et al. In summary, BIS represents a valuable and practical tool for the early detection of subclinical BCRL in patients undergoing prospective monitoring. In this prospective surveillance study, use of BIS allowed for early intervention and a reduction in the predicted rate of chronic BCRL compared to historical controls (no cases of persistent, chronic BCRL were observed after early intervention even in the highest risk patients). Such an approach represents not only a valuable strategy to address the recent NCCN guidelines on survivorship for monitoring for BCRL but also a cost-effective strategy to prevent and manage the potentially devastating effects of chronic BCRL. Link to paper Yes
6 The Impact of L-Dex Measurements in Assessing Breast Cancer-Related Lymphedema as Part of Routine Clinical Practice Laidley, M., Alison and M. Anglin, Beth, The Impact of L-Dex® Measurements in Assessing Breast Cancer Related Lymphedema (BCRL) as Part of Routine Clinical Practice. Frontiers in Oncology, 2016. 6(192). Laidley, A., Anglin B. In summary, BIS represents a valuable and practical tool for the early detection of subclinical BCRL in patients undergoing prospective monitoring. In this prospective surveillance study, use of BIS allowed for early intervention and a reduction in the predicted rate of chronic BCRL compared to historical controls (no cases of persistent, chronic BCRL were observed after early intervention even in the highest risk patients). Such an approach represents not only a valuable strategy to address the recent NCCN guidelines on survivorship for monitoring for BCRL but also a cost-effective strategy to prevent and manage the potentially devastating effects of chronic BCRL. Link to paper Yes
7 The importance of detection of subclinical lymphedema for the prevention of breast cancer-related clinical lymphedema after axillary lymph node dissection; a prospective observational study. Soran, A., et al., The importance of detection of subclinical lymphedema for the prevention of breast cancer-related clinical lymphedema after axillary lymph node dissection; a prospective observational study. Lymphat Res Biol, 2014. 12(4): p. 289-94. Soran, A., Ozmen, T. et al. Periodic monitoring of women at high risk for LE with BIS allows early detection and timely intervention for LE, which reduces the incidence of clinical LE from 36.4% to 4.4%. This may have implications for quality of life and health care costs. Link to paper No
8 The use of Bioimpedance Spectroscopy to Monitor Therapeutic Intervention in Patients Treated for Breast Cancer Related Lymphedema. Shah, C., et al., The use of bioimpedance spectroscopy to monitor therapeutic intervention in patients treated for breast cancer related lymphedema. Lymphology, 2013. 46(4): p. 184-92. Shah C, Vicini F, Beisch P, et al. BIS detected increases in L-Dex scores early after breast surgery and reductions in L-Dex scores as a response to lymphedema treatment. These results demonstrate that BIS conducted in breast cancer clinical settings can be utilized to objectively identify early onset lymphedema and to aid clinicians in monitoring the efficacy of therapeutic intervention in patients treated for BCRL. Further prospective studies are underway to validate these findings. Link to paper Yes
9 Five Year Preliminary Outcomes of a Prospective Surveillance Model to Reduce Upper Extremity Morbidity Related to Breast Cancer Treatment. Stout Gergich, N.L.P., L, et al., Five Year Preliminary Outcomes of a Prospective Surveillance Model To Reduce Upper Extremity Morbidity Related to Breast Cancer Treatment. Cancer Research, 2011. 71(24): p. 1s-653s. Stout This study clearly demonstrates the potential for substantial reduction in UE dysfunction related to breast cancer treatment when using an early identification and intervention model. Morbidity such as pain, reduced range of motion, decreased strength and sub-clinical lymphedema were detected early and managed through the prospective model. These results strongly suggest that prospective surveillance monitoring for functional impairments is an optimal construct to assure long-term function in women after breast cancer treatment. Link to paper Yes
10 Time Course of Mild Arm Lymphedema After Breast Conservation Treatment for Early Stage Breast Cancer. Bar Ad, V., 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): p. 85-90. Bar Ad V, Cheville A, Solin LJ, et al. Mild arm lymphedema can progress to more severe edema, which impacts QoL and function in a significant fraction of breast cancer survivors. This finding mandates a careful follow-up of patients already identified with mild edema and early intervention to attempt to prevent worsening of this potentially not-so-mild complication. Link to paper No
11 Arm lymphoedema in a cohort of breast cancer survivors 10 years after diagnosis. Johansson, K. and E. Branje, Arm lymphoedema in a cohort of breast cancer survivors 10 years after diagnosis. Acta Oncologica, 2010. 49(2): p. 166-173. Johansson K,Branje E. In conclusion, the present study shows that BCRL can be identified at an early stage both in regard to time of diagnosis after operation and to edema volume, and that edema volume can be kept at a low level for a long time. The future challenge in this area will be to improve objective measurements and to validate subjective ones for early identification of BCRL. Link to paper Yes
12 Effectiveness of early physiotherapy to prevent lymphoedema after surgery for breast cancer: randomized, single blinded, clinical trial. Torres Lacomba, M., et al., Effectiveness of early physiotherapy to prevent lymphoedema after surgery for breast cancer: randomized, single blinded, clinical trial. BMJ, 2010. 340: p. b5396. Torres Lacomba M, Yuste Sanchez MJ, Zapico Goni A, et al. Early physiotherapy could help to prevent and reduce secondary lymphoedema in patients after breast cancer surgery involving dissection of axillary lymph nodes, at least for one year after surgery. This result emphasises the role of physiotherapy in the awareness, prevention, early diagnosis, and treatment of secondary lymphoedema. Link to paper Yes
13 Prospective Evaluation of a Prevention Protocol for Lymphedema following Surgery for Breast Cancer. Boccardo, F.M., et al., Prospective evaluation of a prevention protocol for lymphedema following surgery for breast cancer. Lymphology, 2009. 42(1): p. 1-9. Boccardo FM, Ansaldi F, Belini C. The qualitative results of this study suggest that the strategies incorporated into the preventive protocol for prevention as well as early intervention of secondary lymphedema do influence the occurrence and severity of secondary lymphedema in the PG women compared to those in CG. At 24 months after breast cancer surgery, the CG
women had four times the incidence of secondary lymphedema compared to the PG, and in two-thirds of the CG women it was detected at 6 months postoperatively.
Link to paper Yes
14 Preoperative assessment enables the early diagnosis and successful treatment of lymphedema. Stout Gergich, N.L., et al., Preoperative assessment enables the early diagnosis and successful treatment of lymphedema. Cancer, 2008. 112(12): p. 2809-19. Stout Gergich, N. L., L. A. Pfalzer, et al. In conclusion, preoperative assessment in the context of a prospective surveillance model enables the early detection and management of subclinical LE. An early intervention protocol with 20- to 30-mmHg compression garments, as outlined in this report, significantly reduces the affected limb volume to near baseline measures and prevents progression to a more advanced stage of LE for at least the first year postoperatively. Further research is warranted to con-firm the long-term clinical and cost effectiveness of this surveillance model compared with a traditional impairment-based model in treating BC-LE. Link to paper Yes
15 Edema Volume, Not Timing, is the Key to Success in Lymphedema Treatment. Ramos, S.M., L.S. O’Donnell, and G. Knight, Edema volume, not timing, is the key to success in lymphedema treatment. Am J Surg, 1999. 178(4): p. 311-5. Ramos SM, O’Donnell LS, Knight G. Our findings show that no matter what the duration of LE nor the number of treatment visits, those patients having the lowest volumes of edema fluid have the best chance for a successful outcome. Link to paper No
16 The importance of detection of subclinical lymphedema for the prevention of breast cancer-related clinical lymphedema after axillary lymph node dissection; a prospective observational study. Lymphat Res

Biol 12(4): 289-294

Soran, A.,Ozmen, T. et al. 180 patients with breast cancer diagnosis and ALND. Comparison of 3 patient groups: (i) “Pre-op” – L-Dex pre-op and at follow-up (n=72), (ii) “Control” – L-Dex pre-op and only tape measure at follow-up (n=44) and (iii) “No pre-op” – no pre-op assessment L-Dex and tape measure at follow-up (n=64). Groups well matched but no randomization. Detection of LE in early subclinical phase and timely intervention led to a reduction in the incidence of clinical LE incidence from 36.4% to 4.4%.
17 Bioelectrical Impedance for Detecting and Monitoring Lymphedema in Patients with Breast Cancer. Preliminary Results of the Florence Nightingale Breast Study Group. Lymphat Res Biol 2014 (Epub ahead of print) Erdogan Iyigun, Z., et al., 37 patients who underwent surgery for early-stage breast cancer were followed for lymphedema. L-Dex measures taken pre-op, 3, 6, 9 and 12 months post op. 8 patients (21.6%) were identified as having lymphedema, 3 at stage 0, 2 at stage 1 and 3 at stage 2. Intervention resulted in symptomatic improvement for all except one patient. This patients was identified at stage 1 and was non-compliant with therapy and progressed to stage 2. It was concluded that regular monitoring of high-risk patients improves treatment results.
18 The use of Bioimpedance Spectroscopy to Monitor Therapeutic Intervention in Patients Treated for Breast Cancer Related Lymphedema. Lymphology

2013;46:184-92.

Shah C, Vicini F, Beisch P, et al. Retrospective analysis of 50 patients comparing those that underwent BCRL treatment to those that did not. L-Dex scores significantly reduced in those treated and for those with elevated post-operative L-Dex scores, significant reduction with intervention as well. BIS able to detect early onset BCRL and observe treatment response.
19 Five Year Preliminary Outcomes of a Prospective Surveillance Model to Reduce Upper Extremity Morbidity Related to Breast Cancer Treatment. San Antonio Breast Conference, 2011 Stout 5 year update, Stout 2008: Incidence of lymphedema was 7%-22% at 12 months and 11%-38% at 60 months. 12 month to 60 month comparison by stage: Stage 0: 22% vs 38%; Stage I/II: 7% vs 11%; Stage III: 0% vs 0%, respectively. Preliminary data demonstrates long term benefits for early subclinical treatment of patients. “Preoperative assessment, prospective surveillance, and early intervention enhance function and reduces morbidity. Early assessment and intervention should be the standard of care for patients receiving breast cancer treatment.”
20 Arm lymphoedema in a cohort of breast cancer survivors 10 years after diagnosis. Acta Oncol

2010;49:166-173

Johansson K,Branje E. Retrospective study of 292 patient with breast cancer treated with ALND and RT. Those with BCRL were followed for up to 10 years (n=98) with water displacement and volumes kept at a low level throughout. Small volume at diagnosis important to prevent progression.
21 Effectiveness of early physiotherapy to prevent lymphoedema after surgery for breast cancer: randomised, single blinded, clinical trial. BMJ

2010;340:b5396.

Torres Lacomba M, Yuste Sanchez MJ, Zapico Goni A, et al. Randomized trial of 120 women with breast cancer treated with either early physiotherapy and education or education only. At one year, development of BCRL in 7% with interventions vs. 25% without (p=0.01), BCRL diagnosed 4 times more frequently.
22 Time Course of Mild Arm Lymphedema After Breast Conservation Treatment for Early Stage Breast Cancer. Int J Radiat Oncol Biol Phys 2010;76:85-90. Bar Ad V, Cheville A, Solin LJ, et al. Study of 109 patients with BCRL following BCT with mild arm edema (2 cm or less). Freedom from progression 79% at 1 year, 66% at 3 years, 52% at 5 years. Risk of progression even with low volumes.
23 Prospective Evaluation of a Prevention Protocol for Lymphedema following Surgery for Breast Cancer. Lymphology

2009;42:1-9.

Boccardo FM, Ansaldi F, Belini C. Randomized trial of 55 women with breast cancer undergoing ALND; patients were randomized to preventative protocol (lymphoscintigraphy, edema minimization protocol, and early management) or not. At 2 years, 8% developed BCRL (> 200 mL) as compared with 33% in the control group.
24 Preoperative assessment enables the early diagnosis and successful treatment of lymphedema. Cancer

112(12): 2809-2819.

Stout Gergich, N. L., L. A. Pfalzer, et al. Prospective trial of 196 patients, 43 of whom were identified to have BCRL. Compression sleeve given to those with 3% or greater increase in volume (perometry) for 4 weeks. Time to onset 6.9 months post-operatively with intervention associated with a 48 mL reduction that was maintained after intervention. “In conclusion, preoperative assessment in the context of a prospective surveillance model enables the early detection and management of subclinical LE. An early intervention protocol with 20- to 30-mm Hg compression garments, as outlined in this report, significantly reduces the affected limb volume to near baseline measures and prevents progression to a more advanced stage of LE for at least the first year postoperatively.”
25 Lymphoedema secondary to breast cancer: Possibility of diagnostic and therapeutic prevention. Ann Ital Chir 2002;73:493-8.8 Campisi BC, Boccardo F, Zill A, et al. Randomized trial of 50 women with breast cancer randomizing patients to lymphoscintigraphy or normal clinical follow up. Those with lymphoscintigraphy abnormalities provided treatment prior to clinical BCRL development. Subsequent development of clinically evident BCRL in 8% vs. 36% in control group.
26 Edema Volume, Not Timing, is the Key to Success in Lymphedema Treatment. Am J Surg

1999;178:311-5.

Ramos SM, O’Donnell LS, Knight G. 69 patients were analyzed for response to decongestive therapy with little correlations shown between duration and volume or duration and response to treatment. However, initial volume corresponds with response. Less than 250 ml leads to 78% reduction vs. 56% with 250-500 ml.

Implementation/Feasibility

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Open Access

1 Bioelectrical impedance self-measurement protocol development and daily variation between healthy volunteers and breast cancer survivors with lymphedema. Ridner, S.H., et al., Bioelectrical impedance self-measurement protocol development and daily variation between healthy volunteers and breast cancer survivors with lymphedema. Lymphat Res Biol, 2014. 12(1): p. 2-9 Ridner SH, Bonner CM, Doersam JK, et al. Home self-measurement using SFBIA is feasible, acceptable, and captures change. This has implications for both self-care support and the possibility of incorporating self-measurement using SFBIA in future clinical trials examining effectiveness of lymphedema treatment. Based upon findings that volunteers with lymphedema felt daily measurements were too burdensome and examination of patterns in the variation of daily L-Dex values amongst that group when compared to healthy volunteers, we believe that self-measurement every 3 days by BCS-LE is feasible and may be beneficial. Link to paper Yes
2 Bioelectrical Impedance for Detecting and Monitoring Patients for the Development of Upper Limb Lymphedema in the Clinic. Vicini, F., et al., Bioelectrical impedance for detecting and monitoring patients for the development of upper limb lymphedema in the clinic. Clin Breast Cancer, 2012. 12(2): p. 133-7. Vicini F, Shah C, Lyden, M, et al. These findings suggest that BI can be used outside laboratory settings to evaluate breast cancer–related lymphedema in the community oncology setting with relative ease and simplicity. Use of BI increased visits by 5 minutes and use of a standardized protocol was easily incorporated into the office workflow. Further BI has the sensitivity to detect differences in extracellular fluid volume within 90 days of surgery, which allowed for the potential diagnosis of BCRL in the subclinical phase; however, further studies are needed on larger patient sets to validate these findings. Link to paper No
3 Bioimpedance Analysis in the Assessment of Lymphoedema Diagnosis and Management Rockson, S.G., Bioimpedance analysis in the assessment of lymphoedema diagnosis and management. Journal of Lymphoedema, 2007. 2(1): p. 44-8. Rockson SG. In prospective evaluations to date, the assessment of lymphoedema by MFBIA has been found to be rapid, accurate, consistent and well accepted by patients and practitioners. Its utility is increasingly acknowledged. The commercial availability of MFBIA spectrometers designed for specific lymphoedema application should encourage more widespread use, both in research and in practice. As discussed, MFBIA is likely to occupy a central role in the future approaches to lymphoedema risk management , diagnosis and therapeutic monitoring. Link to paper Yes
4 Bioelectrical impedance self-measurement protocol development and daily variation between healthy volunteers and breast cancer survivors with lymphedema. Lymphat Res Biol 2014;12:2-9. Ridner SH, Bonner CM, Doersam JK, et al. Pilot study demonstrates feasibility of incorporating home self assessment with BIS.
5 Bioelectrical Impedance for Detecting and Monitoring Patients for the Development of Upper Limb Lymphedema in the Clinic. Clin Breast Cancer2012;12:133-7. Vicini F, Shah C, Lyden, M, et al. Study of 64 patients evaluated with BIS. Provides information on implementation of BIS into clinic and demonstrates feasibility of utilizing BIS to make clinical decisions based on aggressiveness of locoregional therapy.
6 Bioimpedance Analysis in the Assessment of Lymphoedema Diagnosis and Management Journal of Lymphoedema 2007;2:44-8. Rockson SG. MFBIA (BIS) in analysis of lymphedema has been proven to be fast, accurate and well accepted by patients. Will provide good standard for lymphedema detection and tracking.
7 The Impact of L-Dex Measurements in Assessing Breast Cancer-Related Lymphedema as Part of Routine Clinical Practice Front. Oncol., 05 September 2016 | http://dx.doi.org/10.3389/fonc.2016.00192 Laidley, A., Anglin B.
  • This is a retrospective analysis of 326 patients who underwent pre and post-operative L-Dex measurements with median follow up of 21.7 months.
  • Patients who were asymptomatic whose L-Dex scores increased by >10 points as compared to their baseline scores were identified as having BCRL.
  • Patients were stratified by sentinel lymph node biopsy (n=210) and axillary lymph node dissection (n=116) as well as receipt of BCRL treatment.
  • The cumulative incidence rate of subclinical lymphedema was as follows:
    • 4.3% for SLNB
    • 26.7% for ALND
  • BCRL was identified by L-Dex in 40 patients (12.3%)
    • 50% of these resolved following treatment
    • 27.5% underwent treatment without resolution
    • 22.5% had resolution without treatment
  • Persistent clinical lymphedema
    • 0.5% for SLNB
    • 8.6% for ALND
Diagnostic Comparison

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Open Access

1 Correlation of L-Dex Bioimpedance Spectroscopy with Limb Volume and Lymphatic Function in Lymphedema Coroneos, C.J., et al., Correlation of L-Dex Bioimpedance Spectroscopy with Limb Volume and Lymphatic Function in Lymphedema. Lymphat Res Biol, 2018 Coroneos, C.J., et al. The L-Dex ratio correlated with limb volume and clinical assessment of pitting edema, and physiologic measures of lymphatic function, and demonstrated face, construct, and criterion validity in response to intervention. These findings support the adjunctive use of the L-Dex ratio with limb volume measurements for objective diagnosis, evaluation of lymphedema severity, longitudinal serial evaluation of lymphedema, and response to conservative and surgical interventions. Link to paper No
2 L-Dex ratio in detecting breast cancer-related lymphedema: reliability, sensitivity, and specificity. Fu, M.R., et al., L-Dex ratio in detecting breast cancer-related lymphedema: reliability, sensitivity, and specificity. Lymphology, 2013. 46(2): p. 85-96. Fu MR, Cleland CM, Guth AA, et al. Findings from our study showed that the BIA using L-Dex ratio was significantly related to interlimb volume difference by sequential circumferential tape measurement using the most commonly accepted definition of lymphedema as a 200-mL difference in limb volume when comparing the affected and unaffected limb. BIA was able to accurately discriminate healthy women, breast cancer survivors with lymphedema and at-risk survivors. Our study supports that cross-sectional assessment of BIA by Imp XCA® is a reliable measure for detecting arm lymphedema following breast cancer treatment with good sensitivity and specificity. The BIA by Imp XCA® is easy to operate and time-efficient, which makes it easy to adopt for clinical practice. In addition, the L-Dex ratio takes into consideration of the differences between dominant and non-dominant limbs, making it easy for clinicians to interpret the results, especially using the dichotomized L-Dex ratio of >+7.1 for lymphedema diagnosis. To lessen breast cancer survivors’ worry about lymphedema development, the BIA may have a role in clinical practice by adding confidence in the detection of arm lymphedema among breast cancer survivors even when pre-surgical BIA baseline measures are not available. Finally, we recommend using the best cutoff point of L-Dex ratio >+7.1 instead of L-Dex >+10 to avoid missing a large number of false non-lymphedema cases when pre-surgical BIA baseline are not available. It should be noted that using the cutoff point of >+7.1 still misses 20% of true lymphedema cases. Given that lymphedema is a progressive and debilitating condition and early treatment usually leads to better clinical outcomes, it is important for clinicians to integrate other assessment methods (such as self-report, clinical observation, or perometry) to ensure accurate detection and diagnosis of lymphedema. Link to paper Yes
3 Determining the precision of dual energy x-ray absorptiometry and bioelectric impedance spectroscopy in the assessment of breast cancer-related lymphedema. Newman, A.L., et al., Determining the precision of dual energy x-ray absorptiometry and bioelectric impedance spectroscopy in the assessment of breast cancer-related lymphedema. Lymphat Res Biol, 2013. 11(2): p. 104-9. Newman AL, Rosenthall L, Towers A, et al. In conclusion, DXA and BIS are two tools with good precision for research and clinical assessment of breast cancerrelated lymphedema. This finding is essential for us to acquire greater insight into the changes in tissue composition occurring with the progression of BCRL and for the development of novel treatments for this chronic condition. Link to paper No
4 Segmental measurement of breast cancer-related arm lymphoedema using perometry and bioimpedance spectroscopy. Czerniec, S., et al., Segmental measurement of breast cancer-related arm lymphoedema using perometry and bioimpedance spectroscopy. Support Care Cancer, 2010. Czerniec SA, Ward LC, Lee MJ, et al. BIS can be used for localised measurement of lymphoedema. This technique will enable focal lymphoedema to be detected before measurable volumetric changes. Link to paper No
5 Does the Effect of Weight Lifting on Lymphedema Following Breast Cancer Differ by Diagnostic Method; Results of a Randomized Controlled Trial. Hayes, S.C., et al., Does the effect of weight lifting on lymphedema following breast cancer differ by diagnostic method: results from a randomized controlled trial. Breast Cancer Res Treat, 2011. Hayes SC, Speck RM, Reimet E, et al. In summary, although the quest for identifying the gold standard in measuring lymphedema continues, current various diagnostic methods can be used to our advantage. The PAL trial and the lymphedema characteristics of the participants highlight the importance of using multiple diagnostic methods to comprehensively evaluate the impact of an intervention (within the research or clinical setting) on lymphedema. Future lymphedema research must consider the potential impact of their method of lymphedema measurement and discuss their findings in light of the measure(s) used. Only then will we be better placed to understand which prevention and treatment strategies truly are effective and safe. Link to paper No
6 Comparison of Diagnostic Accuracy of Clinical Measure of Breast Cancer Related Lymphedema: Area Under the Curve. Smoot, B.J., J.F. Wong, and M.J. Dodd, Comparison of diagnostic accuracy of clinical measures of breast cancer-related lymphedema: area under the curve. Arch Phys Med Rehabil, 2011. 92(4): p. 603-10. Smoot BJ, Wong JF, Dodd MJ. A challenge faced by researchers and clinicians is to determine and use diagnostic methods that accurately identify as many true-positive cases of BCRL as possible. Mild cases may potentially be missed when using current diagnostic decision thresholds that have low sensitivity and areas under the ROC curve. There continues to be a need to investigate appropriate diagnostic cutoff scores to identify lymphedema correctly. Of the objective measures used in this study to evaluate lymphedema, circumference was the least accurate in identifying previously diagnosed lymphedema. BIS and volume calculated from circumference were the most accurate. BIS is easy to use, reliable, and accurate. Because differences in impedance represent differences in extracellular volume, BIS may be more a more appropriate measure of BCRL. Link to paper Yes
7 Assessment of Breast Cancer-Related Arm Lymphedema—Comparison of Physical Measurement Methods and Self-Report. Czerniec, S.A., L.C. Ward, and S.L. Kilbreath, Assessment of breast cancer-related lymphedema: a comparison of moisture meter and spot bioimpedance measurement. Lymphat Res Biol, 2015. 13(1): p. 10-9. Czerniec SA, Ward LC, Regshauge KM, et al. Both TDC and spot bioimpedance may have a role in clinical assessment of tissue compositional change in BCRL. Their relationship with tissue composition, assessed by imaging, is now required. Link to paper No
8 Correlation between Bioelectrical Spectroscopy and Perometry in Assessment of Upper Extremity Swelling. Jain, M.S., J.V. Danoff, and S.M. Paul, Correlation between bioelectrical spectroscopy and perometry in assessment of upper extremity swelling. Lymphology, 2010. 43: p. 85-94. Jain MS, Danoff JV, Paul SM. This study confirms the reliability of BIS and its concurrent validity when compared to perometry based on a sample of 10 women who were susceptible to the development of lymphedema. It supports an earlier study by Ward et al (29) who demonstrated a positive correlation (r=0.926) in patients with lymphedema between these measures by inverting the impedance ratios (unaffected compared to affected) before correlating with the perometry data. BIS appears to be sensitive to changes of extracellular and intracellular fluid and may be a useful instrument for clinical assessment of patients prone to lymphedema. Interpretation of impedance and how it relates to conditions within the body will require additional clinical investigation, and further studies will be necessary to substantiate the use of BIS for early detection of lymphedema and for use in other edematous conditions Link to paper Yes
9 Operational Equivalence of Bioimpedance Indices and Perometry for the Assessment of Unilateral Arm Lymphedema. Ward, L.C., S. Czerniec, and S.L. Kilbreath, Operational equivalence of bioimpedance indices and perometry for the assessment of unilateral arm lymphedema. Lymphat Res Biol, 2009. 7(2): p. 81-5. Ward LC, Czerniec S, Kilbreath SL. In conclusion, both approaches are suitable for assessment of lymphedema. Each has their own advantages and disadvantages. Both are rapid to perform and involve minimal inconvenience to the subject. Both methods require little technical training for the operator. A disadvantage of perometry is that the equipment is more expensive to purchase and is not readily portable, although a portable device is in development. In contrast, impedance instruments are less expensive hand-held devices which are readily usable in the field. For some, a perceived disadvantage of the impedance technique may be that lymphedema is quantified as an index rather than in the more familiar units of volume. The very strong correlation between impedance measurement and volume measurement implies that it should be possible to transform impedance data to volume measurement. Indeed, while this is possible, it is not advised owing to concern over the validity of the assumptions upon which these transformations are based. Furthermore, the relatively poor limits of agreement indicate that the two methods, however, could not be used interchangeably. Finally, the impedance technique would appear to be most suited for the early detection of or monitoring of the early stage of lymphedema when the changes are predominantly in extracellular fluid volume. Link to paper No
10 Quantitative bioimpedance spectroscopy for the assessment of lymphoedema. Ward, L.C., S. Czerniec, and S.L. Kilbreath, Quantitative bioimpedance spectroscopy for the assessment of lymphoedema. Breast Cancer Res Treat, 2009. 117(3): p. 541-7. Ward LC, Czerniec S, Kilbreath SL. It is possible, with certain assumptions, to convert impedance to quantitative measures of volume. In addition, BIS, or its single frequency equivalent, is most appropriately used for early detection of or monitoring of the early stage of lymphoedema when the changes are predominantly in extracellular fluid volume. Link to paper No
11 Lymphedema secondary to breast cancer: how choice of measure influences diagnosis, prevalence, and identifiable risk factors. Hayes, S., et al., Lymphedema secondary to breast cancer: how choice of measure influences diagnosis, prevalence, and identifiable risk factors. Lymphology, 2008. 41(1): p. 18-28. Hayes S, Janda M, Cornish B, et al. These findings are derived from a population-based study which, due to slightly lower participation rates among women with more advanced disease and aggressive treatment, may underestimate the true rates of lymphedema present in the breast cancer population. A significant strength of this work was the ability to compare prevalence, cumulative burden and identified risk factors when lymphedema status was measured on the same group using three different methods. In doing so, the results challenge our current understanding regarding lymphedema following breast cancer, in particular the relationship between specific personal, treatment and behavioral characteristics and lymphedema. Since this is the first time lymphedema has been diagnosed using the BIS method in a longitudinal study, further replication is warranted. Perhaps most importantly, these findings highlight the need to establish consensus on lymphedema diagnosis (method and criteria). Anecdotally, circumference methods are the most popular for diagnosing lymphedema in clinical practice. This is supported by the cumulative burden data showing that self-report of a clinical diagnosis of lymphedema over the medium term was 20%, which approximates that calculated with the SOAC method. However, our sensitivity analyses raise concern for the potential to under-diagnose lymphedema using this technique, particularly when research is emerging that early diagnosis may result in more effective treatment. Link to paper No
12 Reliability of Bioimpedance Spectroscopy and Tonometry after Breast Conserving Cancer Treatment. Moseley, A. and N. Piller, Reliability of bioimpedance spectroscopy and tonometry after breast conserving cancer treatment. Lymphat Res Biol, 2008. 6(2): p. 85-7. Moseley A, Piller N. The reliability of these two measurement techniques provides an opportunity for researchers and clinicians to easily quantify breast tissue and fluid changes which in turn may lead to the earlier diagnosis and targeted treatment of breast edema and lymphedema. Link to paper No
13 Bioelectrical Impedance Analysis: Proven Utility in Lymphedema Risk Assessment and Therapeutic Monitoring. Ward, L.C., Bioelectrical impedance analysis: proven utility in lymphedema risk assessment and therapeutic monitoring. Lymphat Res Biol, 2006. 4(1): p. 51-6. Ward LC. Assessment of lymphedema by BIA has been found to be faster, more consistent, and better accepted by clinicians, therapists, and patients than serial tape measurements or water displacement methods. The equipment is highly portable, relatively inexpensive, and is easy to use by nonspecialist personnel. It is still a novel technique that is only now finding a place in the armoratorium of clinical practice. Its usefulness is acknowledged—“This trial confirms that perometry and bioimpedance were both effective in independently showing a reduction in leg lymphedema . . . and that both methods can be reliably used to measure and follow leg lymphedema.” Undoubtedly, we will see more publications in the future attesting to its value in lymphedema assessment. Link to paper No
14 Comparison of methods to diagnose lymphoedema among breast cancer survivors: 6-month follow-up. Hayes, S., B. Cornish, and B. Newman, Comparison of methods to diagnose lymphoedema among breast cancer survivors: 6-month follow-up. Breast Cancer Res Treat, 2005. 89(3): p. 221-6. Hayes, S., B. Cornish, and B. Newman These are preliminary findings, represent cross-sectional relationships between lymphoedema and a variety of characteristics, and statistical power was limited. Continued research is required utilising greater subject numbers before we can better understand the key risk factors for lymphoedema. Nevertheless, this study includes a representative sample and therefore the conclusions derived from this work are likely generalisable to the wider population of women with unilateral breast cancer, aged 75 years or less and residing within 100 km of Brisbane. Clinical characteristics are provided to assist in determining whether the findings are potentially relevant to women in other geographic areas. Perhaps most importantly, these results highlight that the method used to measure and diagnose lymphoedema significantly influences prevalence estimates as well as the identification of potential risk factors. This work also raises questions about the use of circumferences as
the choice of measurement for lymphoedema in both research and clinical settings.
Link to paper No
15 Bioelectrical impedance for monitoring the efficacy of lymphoedema treatment programmes. Cornish, B.H., et al., Bioelectrical impedance for monitoring the efficacy of lymphoedema treatment programmes. Breast Cancer Res Treat, 1996. 38(2): p. 169-76 Cornish BH, Bunce IH, Ward LC, et al. This study has undertaken the most extensive analysis to date of relationships between TBW (and ECW) and individual impedances obtained at different frequencies ( > 400 frequencies), and has shown marginal advantages of using one frequency over another, even if values predicted from theoretical bioimpedance models are used in the estimations. However in situations where there are disturbances of fluid distribution, values predicted from the Cole-Cole analysis of swept frequency bioimpedance measurements could prove to be more useful. Link to paper No
16 L-Dex ratio in detecting breast cancer-related lymphedema: reliability, sensitivity, and specificity. Lymphology 2013;46:85-96. Fu MR, Cleland CM, Guth AA, et al. Study of 250 women including healthy patients, patients with BCRL, and those at risk to develop BCRL. Bioimpedance found to be reliable in healthy women, those at risk and those with BCRL. Correlated with limb circumference.
17 Determining the precision of dual energy x-ray absorptiometry and bioelectric impedance spectroscopy in the assessment of breast cancer-related lymphedema. Lymphat Res Biol 2013;11:104-9. Newman AL, Rosenthall L, Towers A, et al. Study of 24 women with BCRL. Compared DXA and BIS and found both to be precise in measuring lean mass, fat mass, and ECF volume.
18 Does the Effect of Weight Lifting on Lymphedema Following Breast Cancer Differ by Diagnostic Method; Results of a Randomized Controlled Trial. Breast Cancer Res Treat 2011;130:227-34. Hayes SC, Speck RM, Reimet E, et al. Randomized trial of 295 women with breast cancer comparing 4 diagnostic techniques (water displacement, circumference, BIS, and survey) and comparing weight lifting intervention vs. no weight lifting. BCRL diagnosis varied between 22% and 52%, highlighting difference in sensitivity of diagnostic modalities.
19 Comparison of Diagnostic Accuracy of Clinical Measure of Breast Cancer Related Lymphedema: Area Under the Curve. Arch Phys Mede Rehabil 2011;92:603-10. Smoot BJ, Wong JF, Dodd MJ. Cross-sectional study of women with chronic BCRL (n=70) and no BCRL (n=71). Comparison of past diagnosis by physician and alternative diagnostic techniques. BIS yielded the highest accuracy based on AUC curves in assessing existing BCRL
20 Correlation between Bioelectrical Spectroscopy and Perometry in Assessment of Upper Extremity Swelling. Lymphology 2010;43:85-94. Jain MS, Danoff JV, Paul SM. Study of 10 women treated for breast cancer and found that BIS had high inter and intra-rater reliability and concurrent validity as compared with perometry.
21 Assessment of Breast Cancer-Related Arm Lymphedema—Comparison of Physical Measurement Methods and Self-Report. Cancer Invest 2010;28:54-62. Czerniec SA, Ward LC, Regshauge KM, et al. Study of 51 women, 33 with BCRL and 18 without, examining diagnostic methods (BIS, perometry, self-report, truncated cone). Reliability between methods except self report. However, techniques were not interchangeable. BIS found to be highly reliable.
22 Segmental measurement of breast cancer-related arm lymphoedema using perometry and bioimpedance spectroscopy. Support Care Center 2011;19:703-10. Czerniec SA, Ward LC, Lee MJ, et al. Study of 40 women, 29 with BCRL and 11 without with measurements taken with BIS and perometry. BIS able to detect higher inter-limb ratios than perometry in women lymphedema but not without. Increased sensitivity with BIS.
23 Operational Equivalence of Bioimpedance Indices and Perometry for the Assessment of Unilateral Arm Lymphedema. Lymphat Res Biol 2009;7:81-5. Ward LC, Czerniec S, Kilbreath SL. Study measured impedance in 45 women with BCRL and 21 without and also evaluated volume with perometry. Impedance ratios correlated with perometry volumes.
24 Quantitative bioimpedance spectroscopy for the assessment of lymphoedema. Breast Cancer Res Treat 2009;117:541-7. Ward LC, Czerniec S, Kilbreath SL. Control cohort of women (n=69) utilized to predict arm volumes in women with lymphedema (n=23) and those without (n=13) with comparison to perometry. Arm volumes correlated with those predicted by BIS, with no significant difference in arm size prediction and that measured by BIS. Increase in fluid associated with increase in ECF primarily (60%). This observation concurs with the accepted course of progression of lymphoedema in which the earliest events include accumulation of lymph, an extracellular fluid. The inference can also be drawn that BIS is better suited for monitoring early stage lymphedema, where changes are predominantly in fluid volume.
25 Reliability of Bioimpedance Spectroscopy and Tonometry after Breast Conserving Cancer Treatment. Lymph Res Biol 2008;6:85-7. Moseley A, Piller N. Study of 14 women with breast cancer evaluating reproducibility of tonometry and BIS. Found that the both were reliable and allowed for early detection of fluid increases.
26 Lymphedema secondary to breast cancer: how choice of measure influences diagnosis, prevalence, and identifiable risk factors. Lymphology2008;41:18-28. Hayes S, Janda M, Cornish B, et al. Study of 287 women comparing of different diagnostic techniques (BIS, circumference, self-report) used to identify prevalence/cumulative burden of BCRL following treatment. Difference in prevalence noted by method with 40-60% of cases undetected by circumference or survey that were identified with BIS. Compared with BIS, circumferential measurements had 42% sensitivity and 88% specificity for detection of lymphedema. For self-assessment, the sensitivity was 61% and the specificity was 59%.
27 Bioelectrical Impedance Analysis: Proven Utility in Lymphedema Risk Assessment and Therapeutic Monitoring. Lymphat Res Biol 2006;4:51-6. Ward LC. Variation of repeated assessments (same day) (Average ± Std Dev) – Lymphometer (Bioimpedance ECW ratio): 0.60 ± 15.4%; Tape measure ratio: 2.1 ± 35%; Arm Volume (Tape) : 1.4 ± 31%; Bioelectric impedance measurements using the Lymphometer were: 1) Faster, 2) Better accepted by nursing personnel, 3) More consistent than either serial tape measurements or water displacement methods.
28 Comparison of methods to diagnose lymphoedema among breast cancer survivors: 6-month follow-up. Breast Cancer Res Treat 2005;89:221-6. Cornish BH, Bunce IH, Ward LC, et al. Study of 20 patients with breast cancer and 20 healthy controls assessed with multifrequency bioimpedance. Demonstrate increased sensitivity with MFBIA as compared with circumference standard.
29 Bioelectrical impedance for monitoring the efficacy of lymphoedema treatment programmes. Breast Cancer Res Treat 1996;38:169-76. Cornish BH, Bunce IH, Ward LC, et al. Study of 20 patients with breast cancer and 20 healthy controls assessed with multifrequency bioimpedance. Demonstrate increased sensitivity with MFBIA as compared with circumference standard.
Validation Studies

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1 Bioimpedance in the assessment of unilateral lymphedema of a limb: the optimal frequency. Gaw, R., R. Box, and B. Cornish, Bioimpedance in the assessment of unilateral lymphedema of a limb: the optimal frequency. Lymphat Res Biol, 2011. 9(2): p. 93-9 Gaw R, Box R, Cornish B. R0 has been shown previously as the best measurement frequency to assess lymphedema of the arms, as it is more accurate in measuring the extracellular water content of a limb. The present study has shown that the standard deviation of contralateral limb impedance ratios in a normal population increases as the measurement frequency increases. As such, cut off criteria used to identify the onset of lymphedema also increases and sensitivity is reduced. The spread of the control L-Dex and the L-Dex calculated for both arm and leg test subjects, has also been shown to increase with frequency. The frequency at which an overlap occurs between the lower quartile of the test group L-Dex and the upper quartile of the control group L-Dex begins at about 30 kHz. This results in a decreased sensitivity for the detection of lymphedema above this frequency. A comparison between the L-Dex calculated at 0 kHz and the L-Dex calculated at any non-zero single frequency shows that the mean difference between the methods remains constant over the frequency range in a healthy population and increases in the test lymphedema populations. This demonstrates the importance of using low frequency impedance measurements to provide an accurate assessment of the presence of lymphoedema and provides further supporting evidence that the current frequency used in bioimpedance should be below 30 kHz to accurately assess unilateral lymphedema. The 95% confidence interval was also shown to increase with frequency for each population group. This again shows an improved sensitivity in assessing lymphedema at low measurement frequencies. The many single frequency body composition devices available on the market traditionally measure the impedance at 50 kHz. This study shows that the application of these devices to the assessment of lymphoedema is less sensitive to extracellular fluid changes. It has been demonstrated that changes in the extracellular fluid in unilateral lymphedema patients (both arm and leg) can only be monitored accurately and reliably using bioimpedance devices with BIS capabilities or applied current frequencies below 30 kHz. Link to paper No
2 Confirmation of the Reference Impedance Ratios Used for Assessment of Breast Cancer-Related Lymphedema by Bioelectrical Impedance Spectroscopy. Ward, L., et al., Confirmation of the reference impedance ratios used for assessment of breast cancer-related lymphedema by bioelectrical impedance spectroscopy. Lymphatic Research and Biology, 2011. 9(1): p. 47-51. Ward LC, Dylke E, Czerniec S, et al. In summary, new criterion thresholds for the assessment of BCRL by BIS have been determined. Although statistically different to the established reference values, the magnitude of the difference is sufficiently small to be of no practical clinical consequence. It is concluded that, in accord with the observations of Ridner et al., the present reference thresholds may be used with confidence as markers for lymphedema. Link to paper No
3 Reference ranges for assessment of unilateral lymphedema in legs by bioelectrical impedance spectroscopy Ward, L., et al., Reference ranges for assessment of unilateral lymphedema in legs by bioelectrical impedance spectroscopy. Lymphatic Research and Biology, 2011. 9(1): p. 43-46 Ward LC, Dylke E, Czerniec S, et al. The impedance ratio thresholds for lymphedema of the legs have been established, opening the way for BIS to become established clinically for the early detection and assessment of lower limb lymphedema. Link to paper No
4 Comparing Bioelectrical Impedance Values in Assessing Early Upper Limb Lymphedema after Breast Cancer Surgery. In Vivo 2012;26:863-7. Berlit S, Brade J, Tuschy B, et al. Whole body bioimpedance for 33 women treated for breast cancer. Found good sensitivity and specificity along with high negative predictive value.
5 Confirmation of the Reference Impedance Ratios Used for Assessment of Breast Cancer-Related Lymphedema by Bioelectrical Impedance Spectroscopy. Lymphat Res Biol 2011;9:47-51. Ward LC, Dylke E, Czerniec S, et al. Study of 172 healthy females indicates that impedance ratio thresholds are consistent with those previously identified.
6 Bioimpedance in the assessment of unilateral lymphedema of a limb: the optimal frequency. Lymphat Res Biol2011;9:93-9. Gaw R, Box R, Cornish B. Studied limb impedance in healthy cohort as well as those with upper and lower extremity edema. Found good differentiation between the arm and leg L-Dex measured for lymphedema subjects and the arm and leg L-Dex measured for control subjects up to a frequency of about 30 kHz. Concludes that impedance measurements above a frequency of 30 kHz decrease sensitivity to extracellular fluid and are not reliable for early detection of lymphedema. (The FDA cleared BIS device calculates impedance ratios based on an optimal 0 kHz frequency.)
Guidelines

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1 Bioimpedance Spectroscopy for Breast Cancer Related Lymphedema Assessment: Clinical Practice Guidelines Shah, C., F.A. Vicini, and D. Arthur, Bioimpedance Spectroscopy for Breast Cancer Related Lymphedema Assessment: Clinical Practice Guidelines. Breast J, 2016 Shah, C., Vicini, F. A. and Arthur, D. With increasing data supporting early detection and treatment of BCRL, BIS has emerged as an important diagnostic modality due to its ability to detect subclinical lymphedema. BIS can be utilized as part of routine breast cancer clinical care starting with measurements prior to locoregional therapy and continued as part of survivorship using an increase of 10 to trigger early therapy for BCRL. Link to paper No
2 Recent Advances in Breast Cancer Related Lymphedema Detection and Treatment: White Paper Avon Expert Panel – Lymphedema White Paper Avon Foundation for Women The white paper recommends that breast cancer survivors be closely monitored for the development of lymphedema and learn how to reduce their risk of developing the disorder, such as by recognizing the physical triggers (e.g. cuts or burns on the fingers) that may transform the disease from latent to active and by maintaining meticulous skin care hygiene and a healthy body weight. Recent studies in weight lifting, exercise and weight loss also have demonstrated a benefit in preventing lymphedema: stretching, aerobics and arm and leg weight lifting resulted in fewer flare-ups among patients with lymphedema and reduced the chance of developing the condition among at-risk patients by 70%. Link to paper Yes
3 National Lymphedema Network Position Papers NLN Position Paper – Diagnosis and Treatmetn of Lymphedena National Lymphedema Network Recommend reliable, reproducible assessment technique with standardized cut offs to initiate treatment. Bioelectrical spectroscopy (BIS) represents a reliable technique that can be used to detect early lymphedema. Link to paper Yes
4 National Lymphedema Network Position Papers http://www.lymphnet.org/pdfDocs/nlnBCLE.pdf National Lymphedema Network Recommend reliable, reproducible assessment technique with standardized cut offs to initiate treatment. Bioelectrical spectroscopy (BIS) represents a reliable technique that can be used to detect early lymphedema.
5 Recent Advances in Breast Cancer Related Lymphedema Detection and Treatment: White Paper http://www.avonfoundation.org/assets/le-meeting/le-white-paper.pdf Avon Foundation for Women Recognizes bioimpedance as a new technique that can be utilized for early detection. Notes BIS is validated and economical compared to alternatives used for early detection.
6 Bioimpedance Spectroscopy for Breast Cancer Related Lymphedema Assessment: Clinical Practice Guidelines Breast J. 2016;22(6):645-50. Shah, C., Vicini, F. A. and Arthur, D.
  • The authors put forth Clinical Practice Guidelines in the early detection and management of BCRL based on a review of the available literature and techniques available. Included in the guidelines are;
    • At-risk patients
    • Assessment techniques
    • Protocol (assessment schedule)
    • Intervention
  • BIS has emerged as an important diagnostic tool for the early detection of BCRL due to its ability to detect subclinical disease. It can be utilized as part of routine clinical practice prior to locoregional therapy and continuing through survivorship.
Economics/Quality of Life

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1 Quality of life of women with lower limb swelling or lymphedema 3-5 years following endometrial cancer. Rowlands, I.J., et al., Quality of life of women with lower limb swelling or lymphedema 3-5 years following endometrial cancer. Gynecol Oncol, 2014. 133(2): p. 314-8. Rowlands IJ, Beesley VL, Janda M, et al. In conclusion, we show that both LLL and LLS may limit the physical QoL of long-term endometrial cancer survivors, and the mental QoL of women who report experiencing swelling but who are not diagnosed with LLL. Thus, the emotional and physical well-being of women with lymphedema-like symptoms could be managed better through early referral to evidence-based lymphedema intervention programs, such as those of exercise training, bandaging or elevation [8,41,42]. Ongoing health care attention may be particularly important given the enormous personal and social costs associated with lymphedema. Link to paper No
2 Economic Benefits of BIS-Aided Assessment of post-BC Lymphedema in the United States. Bilir, S.P., M.P. DeKoven, and J. Munakata, Economic benefits of BIS-aided assessment of post-BC lymphedema in the United States. Am J Manag Care, 2012. 18(5): p. 234-41. Billr SP, DeKoven MP, Munakata J. Over 1 year, BIS-aided assessment of lymphedema for patients following treatment for BC results in cost savings, even without considering potential cost savings associated with averted downstream sequelae. Link to paper Yes
3 Incidence, treatment costs, and complications of lymphedema after breast cancer among women of working age: a 2-Year follow-up study. Shih, Y.C., et al., Incidence, Treatment Costs, and Complications of Lymphedema After Breast Cancer Among Women of Working Age: A 2-Year Follow-Up Study. J Clin Oncol, 2009. Shih YC, Xu Y, Cormier JN, et al. Although the use of claims data may underestimate the true incidence of lymphedema, women with BCRL had a greater risk of infections and incurred higher medical costs. The substantial costs documented here suggest that further efforts should be made to elucidate reduction and prevention strategies for BCRL. Link to paper Yes
4 Quality of life of women with lower limb swelling or lymphedema 3-5 years following endometrial cancer. Gynecol Oncol 2014; 133(2): 314-8. Rowlands IJ, Beesley VL, Janda M, et al. Survey of 1399 women with endometrial cancer. Those with lower limb lymphedema/swelling had reduced physical QOL 3-5 years following treatment.
5 Economic Benefits of BIS-Aided Assessment of post-BC Lymphedema in the United States. Am J Manag Care2012:234-41. Billr SP, DeKoven MP, Munakata J. Economic analysis demonstrating that BIS utilization would lead to a cost savings which is magnified when considering sequelae of BCRL.
6 Incidence, treatment costs, and complications of lymphedema after breast cancer among women of working age: a 2-Year follow-up study. J Clin Oncol 2009;27:2007-14 Shih YC, Xu Y, Cormier JN, et al. Claims study of 1,877 patients for 2 years after the start of cancer treatment. 10% of patients developed lymphedema with ALND and chemotherapy associated with development. Higher medical costs associated with BCRL diagnosis ($23, 167 vs. $14,877) with higher rates of cellulitis/lymphangitis noted.
Pathophysiology

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1 Correlation of Bioimpedance Spectroscopy with Risk Factors for the Development of Breast Cancer-Related Lymphedema. Vicini, F., et al., Correlation of Bioimpedance Spectroscopy with Risk Factors for the Development of Breast Cancer-Related Lymphedema. Lymphat Res Biol, 2018. Vicini, F., et al. Risk factors for development of BCRL were associated with both the magnitude and timing of change in L-Dex scores. These findings demonstrate the utility of serial L-Dex measurements in providing an objective assessment of a patient’s lymphedema status and the value of L-Dex serial measurements to assist in monitoring patients for the development of BCRL. This supports the clinical utilization of serial L-Dex scores to follow patients at risk for BCRL. Link to paper Yes
2 Pathophysiology of lymphedema. Ridner, S.H., Pathophysiology of lymphedema. Semin Oncol Nurs, 2013. 29(1): p. 4-11. Ridner SH. “CONCLUSION: Many cancer patients and survivors are at risk for lymphedema that can occur in any area of the body.
IMPLICATIONS FOR NURSING PRACTICE: Nurses should become leaders in the early identification of lymphedema. When caring for patients with lymphedema, nurses should: 1) encourage self-care, 2) provide emotional support, 3) offer patient and lay caregiver education, 4) assess symptoms patients with lymphedema may be experiencing, and 5) develop a plan of management.”
Link to paper No
3 The pathophysiology of lymphedema. Mortimer, P.S., The pathophysiology of lymphedema. Cancer, 1998. 83(12 Suppl American): p. 2798-802. Mortimer PS. The primary insult to the axillary lymphatic system by surgery and radiotherapy is presumably the root cause
of postmastectomy edema (PME), but there is strong evidence to suggest that hemodynamic factors contribute to sustaining edema even if they are not causal. The basic rule that all edemas result from an imbalance between capillary filtration and tissue (lymph) drainage, in itself, demands consideration of the state of the microcirculation as well as of the lymphatic drainage. Total arm blood flow and vascular bed size appear to be increased in PME, factors that will increase capillary filtration in the limb overall. One of the problems in
studying PME is that patients are investigated at one moment in time during an evolving process. The pathophysiology of PME is not simply lymphatic obstruction, and unravelling the complex sequence of events in PME will need research not only on established PME but also at its earlier, latent stage.
Link to paper Yes
4 Pathophysiology of lymphedema. Semin Oncol Nurs 2013;29:4-11. Ridner SH. Lymphedema pathophysiology overview and implications.
5 Current concepts and future directions in the diagnosis and management of lymphatic vascular disease. Vasc Med 2010;15:223-31. Rockson SG. A review of lymphatic biology, pathology and evolving concepts about the diagnostic and therapeutic approaches based on the relevant fluid changes.
6 The pathophysiology of lymphedema. Cancer 1998;83:2798-802. Mortimer PS. Edema represents an increase in interstitial fluid volume sufficient to manifest with swelling. Any edema, whatever the underlying cause, is due to an imbalance between capillary filtration and lymph drainage.
Review Articles

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1 Cancer-Related Lymphedema Risk Factors, Diagnosis, Treatment, and Impact: A Review Paskett, E.D., et al., Cancer-related lymphedema risk factors, diagnosis, treatment, and impact: a review. J Clin Oncol, 2012. 30(30): p. 3726-33. Paskett ED, Dean JA, Oliveri JM, et al. Research into causes, prevention, and effect on QOL of LE and information on LE in cancers other than breast is needed. Consensus on definitions and measurement, increased patient and provider awareness of signs and symptoms, and proper and prompt treatment/access, including psychosocial support, are needed to better understand, prevent, and treat LE. Link to paper Yes
2 Breast Cancer Related Arm Lymphedema: Incidence Rates, Diagnostic Techniques, Optimal Management and Risk Reduction Strategies. Shah, C. and F.A. Vicini, Breast cancer-related arm lymphedema: incidence rates, diagnostic techniques, optimal management and risk reduction strategies. Int J Radiat Oncol Biol Phys, 2011. 81(4): p. 907-14. Shah C, Vicini FA. Significant heterogeneity exists in the literature regarding incidence, diagnosis, and management of BCRL. Surgical, radiation, and chemotherapeutic decisions should be made with insight regarding the incidence of BCRL for each procedure and in combination. Newer diagnosis techniques including DEXA and BIS represent significant improvements over traditional techniques by providing standardized cutoffs, limiting observer variability, increasing sensitivity with the potential of subclinical detection, and accurately measuring the extracellular fluid space. Treatment paradigms have evolved over the last decade with the use of compression sleeves for subclinical disease demonstrating excellent outcomes with minimal morbidity and CDP being used in more advanced cases of BCRL with increasing support in the literature. Long-term outcomes with treatment strategies are limited. Risk reduction strategies need to incorporate treatment and patient factors that increase BCRL and include proactive surveillance and diagnosis to increase the percentage of patients who are diagnosed with subclinical disease. Link to paper No
3 Lymphedema: How Do We Diagnose and Reduce the Risk of This Dreaded Complication of Breast Cancer Treatment? Bernas, M., et al., Lymphedema: How Do We Diagnose and Reduce the Risk of This Dreaded Complication of Breast Cancer Treatment? Current Breast Cancer Reports, 2010. 2(1): p. 53-58. Bernas MJ, Askew RL, Armer JM, et al. Lymphedema is a dreaded condition that can affect cancer survivors long after their definitive treatment. Sometimes more importantly for these patients, it can function as an outward sign to the public of their cancer history. With the increasing use of sentinel lymph node biopsy and some of the more recent prevention/minimization protocols, the incidence of lymphedema caused by surgical dissection is expected to decline. However, a higher risk still remains for those women who have nodal disease requiring axillary dissection and/or radiation therapy. Health care providers involved with cancer patients need to become more educated about lymphedema, aware of current risk reduction practices, and familiar with methods of diagnosis and assessment so that we can identify patients with early swelling for referral to lymphedema treatment specialists at a time when treatment is more effective. Link to paper No
4 Lymphedema: A primer on the identification and management of a chronic condition in oncologic treatment. Lawenda, B.D., T.E. Mondry, and P.A. Johnstone, Lymphedema: a primer on the identification and management of a chronic condition in oncologic treatment. CA Cancer J Clin, 2009. 59(1): p. 8-24. Lawenda BD, Mondry TE, Johnstone PA. Conventional oncologic therapies, including radiation therapy and surgery, have made significant improvements in the outcomes of patients’ lives. Nevertheless, despite numerous advances in techniques to improve outcomes and decrease toxicity, many of these interventions can leave patients with untoward complications, such as lymphedema. Lymphedema is a chronic and incurable condition that must be discussed with each at-risk patient. It is our responsibility as oncologists and patient educators to become familiar with the early signs and symptoms of lymphedema, the basic pathophysiology, prevention/risk reduction behaviors, and general management techniques. There are numerous informational resources available to educate practitioners and patients about lymphedema and to help find reputable lymphedema management specialists (Table 4.) Importantly, with the early identification and management of lymphedema, we can help many of our patients maintain their quality of life by minimizing cosmetic, functional, psychoemotional, and potentially life-threatening complications. Link to paper Yes
5 Addressing the Unmet Needs in Lymphedema Risk Management. Rockson, S.G., Addressing the unmet needs in lymphedema risk management. Lymphat Res Biol, 2006. 4(1): p. 42-6. Rockson SG. Risk stratification and aggressive early intervention may have the capacity to forestall, or even eliminate, the consequences of lymphedema. The elusive aspect of disease latency complicates the identification of high risk patients; therefore, the potential for effective strategies exists, but requires the ability to accurately identify these high risk individuals. Availability of accurate, noninvasive technology for the detection of latent or early disease may facilitate the implementation of preventive strategies. Link to paper No
6 Bioelectrical Impedance Analysis: Proven Utility in Lymphedema Risk Assessment and Therapeutic Monitoring. Ward, L.C., Bioelectrical impedance analysis: proven utility in lymphedema risk assessment and therapeutic monitoring. Lymphat Res Biol, 2006. 4(1): p. 51-6. Ward LC. Assessment of lymphedema by BIA has been found to be faster, more consistent, and better accepted by clinicians, therapists, and patients than serial tape measurements or water displacement methods. The equipment is highly portable, relatively inexpensive, and is easy to use by nonspecialist personnel. It is still a novel technique that is only now finding a place in the armoratorium of clinical practice. Its usefulness is acknowledged—“This trial confirms that perometry and bioimpedance were both effective in independently showing a reduction in leg lymphedema . . . and that both methods can be reliably used to measure and follow leg lymphedema.” Undoubtedly, we will see more publications in the future attesting to its value in lymphedema assessment. Link to paper No
7 Cancer-Related Lymphedema Risk Factors, Diagnosis, Treatment, and Impact: A Review J Clin Oncol 2012;30:3726-33. Paskett ED, Dean JA, Oliveri JM, et al. Review of cancer-related lymphedema with identification of bioimpedance as an emerging diagnostic technique with greater ease and comfort than traditional diagnostics. Notes that lymphedema can significantly impair QOL.
8 Breast Cancer Related Arm Lymphedema: Incidence Rates, Diagnostic Techniques, Optimal Management and Risk Reduction Strategies. Int J Radiat Oncol Biol Phys 2011;81:907-14. Shah C, Vicini FA. “Traditional measures use total arm volume as a surrogate for LE (lymphedema). However, this is not completely accurate because LE represents an increase in the extracellular fluid volume. ….newer modalities can directly measure the extracellular volume, potentially providing increased diagnostic accuracy… Newer diagnosis techniques including DEXA and BIS represent significant improvements over traditional techniques by providing standardized cutoffs, limiting observer variability, increasing sensitivity with the potential of subclinical detection, and accurately measuring the extracellular fluid space.”
9 Lymphedema: How Do We Diagnose and Reduce the Risk of This Dreaded Complication of Breast Cancer Treatment? Current Breast Cancer Reports 2010; 2:53-58 Bernas MJ, Askew RL, Armer JM, et al. Encourages healthcare providers involved with cancer patients to become more educated about lymphedema, aware of current risk-reduction practices, and familiar with methods of diagnosis and assessment, so that patients with early swelling can be referred to lymphedema treatment specialists at a time when treatment is more effective.
10 Lymphedema: A primer on the identification and management of a chronic condition in oncologic treatment. CA Cancer J Clin 2009;59:8-24. Lawenda BD, Mondry TE, Johnstone PA. Review focuses on early identification and management of lymphedema along with pre-surgical assessment of risk. Supports BIS as reliable and accurate measure.
11 Addressing the Unmet Needs in Lymphedema Risk Management. Lymphat Res Biol 2006;4:42-6. Rockson SG. Criteria for early diagnosis of breast cancer related lymphoedema:
12 Bioelectrical Impedance Analysis: Proven Utility in Lymphedema Risk Assessment and Therapeutic Monitoring. Lymphat Res Biol 2006;4:51-6 Ward LC. Supports BIS as a diagnostic modality with potential for earlier detection and feasible implementation into clinic.
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1 Diagnosis of Early and Subclinical Lymphedema Following Breast Cancer Rockson, S.G., Diagnosis of Early and Subclinical Lymphedema Following Breast Cancer. Lymphat Res Biol, 2018. 16(5): p. 425 Rockson SG. From this work, the authors have concluded that, at the time of breast cancer diagnosis, the values for bioimpedance ratios are similar to normative values. Furthermore, identified maximum changes in these values at 12 months suggest that frequent assessment during this index year provides potential benefit. Finally, their work suggests that an even lower threshold than conventionally held might be considered to establish the presence of subclinical lymphedema. Link to paper No
2 Lymphedema after Breast Cancer Treatment Rockson, S.G., Lymphedema after Breast Cancer Treatment. N Engl J Med, 2018. 379(20): p. 1937-1944 Rockson SG. The patient described in the vignette is at increased risk for the development of lymphedema owing to her elevated BMI and her history of axillary lymph-node dissection, nodal metastasis, and radiotherapy. I would recommend a surveillance program that includes quarterly assessment of bioimpedance during this first year after treatment, which is when the majority of cases appear. There should also be prompt use of compression garments and, as necessary, use of decongestive physiotherapy for symptoms or for worrisome changes in bioimpedance. The patient should be encouraged to attain and maintain an ideal body weight through diet and regular exercise. The uncertain merits of conventional risk-reduction behaviors, including the use of a
prophylactic compression sleeve, should be explained to the patient so that she can make informed, personalized decisions as to whether she should incorporate these strategies into her plans for aftercare.
Link to paper No
3 Is BIS ready for prime time as the gold standard measurement? Ward, L., Is BIS ready for prime time as the gold standard measure? Journal of Lymphoedema, 2009. 4(2): p. 52-56. Ward L. Is BIS ready for prime time as the method of choice for lymphoedema detection? Many authors identify lack of standardisation for the detection and evaluation of lymphoedema as an impediment to lymphoedema care and therapy. This article asked the question, ‘Is BIS ready for prime time as a gold standard for lymphoedema detection?’. To this question, my answer is a qualified ‘yes’. A convincing argument can be made that on theoretical grounds, analytical and technical accuracy and precision and practicality in use, impedance technology is the method of choice when compared to competing technologies. The case is well made for its adoption for the assessment of lymphoedema post-breast cancer treatment. It should be acknowledged that impedance ratios, in common with the other assessment modalities, should not be considered as providing the definitive diagnostic criterion. They must always be considered alongside the clinical judgement of the clinician, lymphoedema practitioner or lymphologist. To quote Stanton et al (2006) in relation to BCRL: ‘Careful examination of the arms of patients with breast cancer is vital. Comparison of arm volumes (or circumferences) alone, will not detect early BCRL and will result in an underestimate of its prevalence in studies of the complications of axillary surgery’. Like all technologies, BIS is under constant development and refinement. Pressing needs are for optimisation and thorough validation of the method for quantification of bilateral lymphoedema. Its adoption awaits these further studies. The challenge for the lymphoedema research community is to undertake these studies at the earliest opportunity. Link to paper Yes
4 Is BIS ready for prime time as the gold standard measurement? Journal of Lymphoedema2009;4:52-6. Ward L. Editorial suggests that BIS should be considered new standard for lymphedema assessment due the sensitivity, specificity, and reproducibility of results.