Response to Letter to the Editor: Randomized Trial Assessing Prospective Surveillance and Exercise for Preventing Breast Cancer-Related Lymphedema in High-Risk Patients.

Background: We evaluated the impact of structured surveillance using bioimpedance spectroscopy (BIS) to prevent clinical BCRL in a group of high-risk (axillary lymph node dissection) patients. Methods: From April 2010 through November 2016, 93 patients who were treated with axillary lymph node dissection (ALND) were prospectively monitored with BIS using L-Dex (Impedimed). Patients received a pre-operative baseline L-Dex measurement followed by post-operative assessments at regular intervals. An elevated L-Dex score was defined as an increase of ≥10 points above baseline (considered subclinical BCRL). Intervention consisted of applying an over the counter (OTC) sleeve for 4 weeks followed by re-evaluation. The need for complete decongestive physiotherapy (CDP) represented a surrogate for the development of clinically significant, chronic BCRL. Results: Median follow-up was 24 months (range: 0.3-206.4 months). The median number of nodes removed was 19 (range: 5-41) and the median number of positive nodes was 3. Median age was 53 years old. Eighty five percent of patients underwent mastectomy and the remainder breast conserving therapy. 55% of patients received taxane based chemotherapy, 24% received some form of axillary RT (15% high tangents and 9% comprehensive regional nodal RT) and 74% had an elevated body mass index (BMI, > 25). Overall, 75% of these patients had at least one additional high-risk feature, 48% had at least two, and 6% had 3 (either taxane chemotherapy, axillary RT or elevated BMI). Thirty-three patients (35.4%) developed an elevated L-Dex score at some point during follow up. Overall, 10 patients (11%) required CDP at any point after treatment. Conclusions: The results of this analysis support 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, 11% required CDP. These results compare favorably to all contemporary studies reporting BCRL rates in high-risk patients. Citation Format: Whitworth P, Cooper A, Shah C, Vicini F. The impact of a structured surveillance protocol using bioimpedance spectroscopy (BIS) on preventing breast cancer related lymphedema (BCRL) in high-Risk patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-14-08.

118 Background: Survivorship represents an increasing focus in the management of breast cancer with chronic toxicities including breast cancer-related lymphedema (BCRL). This study looked at prospective surveillance using bioimpedance spectroscopy (BIS) to reduce risks of chronic BCRL requiring referral for complete decongestive therapy (CDT). Methods: 132 patients at high-risk for the development of BCRL were prospectively followed using BIS with serial monitoring. This included a pre-operative baseline assessment and a minimum of two post-operative follow up assessments. Interventions were initiated when the L-Dex score increased by greater than 10 units from baseline and consisted of conservative treatment with a compression sleeve for four weeks. Patients were also clinically monitored for the development of BCRL. Results: Median follow-up was 19.3 months (range 4-54 mos). Of the 132 patients evaluated, 24 (18.1%) were subsequently diagnosed with elevated L-Dex scores and underwent intervention. Of the 24 that underwent treatment, 14 (58%) had resolution of their elevated L-Dex scores following four weeks of therapy with 10 having persistent elevations and clinical BCRL which necessitated referral to physical therapy for CDT. A further 7 subjects were diagnosed and not treated for elevated L-Dex scores, but had complete resolution (return to baseline) at last visit. At last follow-up, only 10 patients (7.6 %) had unresolved, clinical stage 1, BCRL. Conclusions: The use of L-Dex to prospectively follow our high-risk patients and prescribe intervention with a compression sleeve for 4 weeks when scores are elevated resulted in only a 7.6 % rate of stage 1, chronic BCRL. This rate of BCRL has been reported as 15-20%, suggesting that a prospective program of screening and intervention using L-Dex does result in clinically meaningful reductions in this long-term sequelae of treatment.

BackgroundThis analysis was performed to assess the impact of early intervention following prospective surveillance using bioimpedance spectroscopy (BIS) to detect and manage breast cancer-related lymphedema (BCRL).MethodsFrom 8/2010 to 12/2016, 206 consecutive patients were evaluated with BIS. The protocol included pre-operative assessment with L-Dex as well as post-operative assessments at regular intervals. Patients with L-Dex scores >10 from baseline were considered to have subclinical BCRL and were treated with over-the-counter (OTC) compression sleeve for 4 weeks. High-risk patients were defined as undergoing axillary lymph node dissection (ALND), receiving regional nodal irradiation (RNI), or taxane chemotherapy. Chronic BCRL was defined as the need for complex decongestive physiotherapy (CDP).ResultsMedian follow-up was 25.9 months. Overall, 17% of patients had one high-risk feature, 8% two, and 7% had three. 9.8% of patients were diagnosed with subclinical BCRL with highest rates seen following ALND (23 vs. 7%, p = 0.01). Development of subclinical BCRL was associated with ALND and receipt of RNI. At last follow-up, no patients (0%) developed chronic, clinically detectable, BCRL. Subset analysis was performed of the 30 patients undergoing ALND. Median number of nodes removed was 18 and median number of positive nodes was 2. 77% received taxane chemotherapy, 62% axillary RT, and 48% had elevated BMI. Overall, 86% of patients had at least one additional high-risk feature, 70% at least two, and 23% had all three. Seven patients (23%) had abnormally elevated L-Dex scores at some point during follow-up. To date, none has required CDP.ConclusionsThe results of this study support prospective surveillance utilizing BIS initiated pre-operatively with subsequent post-operative follow-up measurements for the detection of subclinical BCRL. Intervention triggered by subclinical BCRL detection with an elevated L-Dex score was associated with no cases progressing to chronic, clinically detectable BCRL even in very high-risk patients.

Background: We report outcomes using prospective BIS surveillance in a high-risk cohort of patients who all underwent axillary lymph node dissection (ALND). Methods: From 8/2010 through 12/2016, 206 consecutive patients were evaluated with BIS as part of a prospective surveillance program. 30 underwent ALND and constitute the study population. The program included pre-operative BIS measurement as well as post-operative assessments at regular intervals. Patients with L-Dex readings increasing by more than 10 from baseline were considered to have subclinical BCRL and treated with an over-the-counter (OTC) compression sleeve for 4 weeks. For the purpose of this analysis, additional high-risk features were defined as receipt of axillary radiation, a high body mass index (BMI) or the use of taxane based chemotherapy. Chronic BCRL was defined as the need for complex decongestive physiotherapy (CDP). Results: Median follow-up was 36 months (range: 4.8-122.1 months). The median number of nodes removed was 18 (range: 5-32) and the median number of positive nodes was two. The median age for the cohort was 57.5 years old with 70% of patients undergoing mastectomy and the remainder breast conserving therapy. With respect to additional high-risk features, 77% also received taxane-based chemotherapy, 62% axillary irradiation, and 48% had an elevated BMI. Overall, 86% of patients had at least one additional high-risk feature, 70% at least two, and 23% had all three additional high-risk features. Seven patients (23%) had an elevated L-Dex score at some point during follow-up and underwent intervention with an OTC sleeve for 4 weeks. To date, no patients have required CDP at any time. Conclusions: Prospective surveillance with BIS in a high-risk cohort of patients all undergoing ALND (plus additional high-risk features) led to no patients requiring CDP. These excellent findings are consistent with growing data supporting the use of BIS in prospective BCRL surveillance programs. Citation Format: Kaufman D, Shah C, Vicini F. Low rates of chronic breast cancer related lymphedema (BCRL) in a cohort of high-Risk patients undergoing prospective surveillance with bioimpedance spectroscopy (BIS) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-14-09.

Background: With improved breast cancer outcomes, an increasing focus on sequelae of treatment as part of survivorship has emerged. Breast cancer related lymphedema (BCRL) represents one such sequelae. Increasing data and recent NCCN guidelines support the use of prospective BCRL surveillance to allow for early detection and intervention as a method to reduce chronic, irreversible BCRL. Therefore, this study was performed to evaluate the impact early detection and treatment of BCRL in breast cancer patients undergoing prospective surveillance with bioimpedance spectroscopy (BIS). Methods: From 8/2010 through 12/2016, 206 patients were evaluated with BIS as part of a prospective surveillance program.The protocol included pre-operative assessment with BIS as well as post-operative assessments with BIS at regular intervals. Patients with L-Dex readings increasing by more than 10 from baseline were considered to have subclinical BCRL and treated with a compression sleeve for 4 weeks. For the purpose of this analysis, high-risk was defined as receipt of ALND, regional nodal irradiation, or taxane chemotherapy. Chronic BCRL was defined as the need for complex decongestive physiotherapy. Results: A total of 206 patients were analyzed, with a mean age of 61 years old and a median follow up of 25.9 months. Overall, 17% of patients had least one high-risk feature, 8% had two factors, and 7% had all three factors. A total of 21 patients (9.8%) were diagnosed with subclinical BCRL. Increased rates of subclinical BCRL were seen in patients undergoing ALND (23% vs. 7%, p=0.01) with ALND and receipt of RNI associated with development of subclinical BCRL. At last follow-up, no patients had persistent, chronic BCRL following early, conservative intervention measures. Conclusions: The results of this study support prospective surveillance and early treatment utilizing BIS. Intervention triggered by subclinical BCRL detection with an elevated L-Dex score was associated with a very low rate of chronic BCRL. Citation Format: Kaufman D, Shah C, Vicini F. Utilization of bioimpedance spectroscopy in the prevention of chronic breast cancer related lymphedema [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-12-03.

Objective: The occurrence of breast cancer-related lymphedema (BCRL) in postoperative breast cancer survivors is described and the independent risk factors of BCRL are analyzed. A BCRL nomogram prediction model is constructed, and its effectiveness is evaluated to screen out high-risk patients with BCRL. Methods: A univariate analysis was carried out to determine the risk factors possibly related to BCRL, and a logistic regression analysis was utilized to determine the independent risk factors related to BCRL. A BCRL nomogram prediction model was built, and a nomogram was drawn by R software v4.1.0. The area under the curve (AUC) of the receiver operating characteristic (ROC) and the Hosmer-Lemeshow test were used to evaluate the efficacy of the constructed model to assess its clinical application value. Results: The risk factors independently associated with BCRL were body mass index (BMI), handedness on the operation side, no BCRL-related rehabilitation plan, axillary lymph node dissection (ALND), taxane-based chemotherapy, and radiotherapy (all p < 0.05). The BCRL nomogram prediction model was built on this basis, and the results of the efficacy evaluation showed a good fit: AUC = 0.952 (95% confidence interval: 0.930-0.973) for the ROC and χ2 = 6.963, p = 0.540 for the Hosmer-Lemeshow test. Conclusions: The risk factors for BCRL included higher BMI, handedness on the operation side, no BCRL-related rehabilitation plan, ALND, taxane-based chemotherapy, and radiotherapy. In addition, the BCRL nomogram prediction model accurately calculated the risk of possible BCRL among breast cancer survivors and effectively screened for high-risk patients with BCRL. Therefore, this prediction model can provide a basis for rehabilitation physicians and therapists to formulate early and individualized prevention and treatment programs.

Randomized Trial Assessing Prospective Surveillance and Exercise for Preventing Breast Cancer-Related Lymphedema in High-Risk Patients.

399 Background: The rural and underserved have unique challenges and barriers to receiving evaluation and treatment for BCRL. Prospective identification and PREHAB for those at high risk including mastectomy over age 60, axillary node dissection, and radiation reduces the risk of BCRL and post-operative treatment encounters. In a rural Virginia breast program in 2021, 71% (40/56) of breast cancer (BC) patients were identified as high-risk for BCRL. Only fifteen percent (6/40) of high-risk patients received PREHAB with fifty-two percent (29/56) of total BC patients required post-operative encounters for treatment of BCRL. A quality improvement project to improve these numbers was implemented. Methods: We sought to increase the number of PREHAB encounters for patients at high-risk for developing BCRL and to decrease the total number of BC patients requiring post-operative BCRL treatment encounters. A Certified Lymphedema Therapist (CLT) prospectively identified patients at high-risk for development of BRCL during multidisciplinary breast cancer conference (MBCC). High-risk patients were offered PREHAB appointments, and the rates of PREHAB and post-operative intervention encounters were recorded. Results: In 2022, 76% (51/67) of BC patients were identified as high-risk for developing BCRL. Thirty-seven percent (19/51) received PREHAB, a 22% increase from 2021. The average number of visits was 7.7 visits for patients who received PREHAB and 19.2 visits for patients who did not. Forty-two percent (28/67) of total BC patients required post-operative encounters for treatment of BCRL, a 10% decrease from 2021. Barriers/Challenges: Both providers and patients showed limited engagement in the PREHAB model at the start of the program. Patient barriers to treatment included transportation and time limitations. Conclusions: A dedicated focus including high-risk screening, PREHAB, and a CLT at MBCC, can improve outcomes for BCRL in a rural and underserved population. Future investigation will include measuring BCRL rates over time.

Background Studies on the efficacy of prescription omega-3 polyunsaturated fatty acids to reduce cardiovascular events have produced conflicting results. Research design and methods This 3-year prospective post-marketing surveillance study evaluated the effect of omega-3-acid ethyl esters (O3AEE; usual dosage 2 g/day) on cardiovascular events in high-risk statin-treated Japanese patients with hypertriglyceridemia. Statin-treated patients not receiving O3AEE were included as a reference cohort. The composite primary endpoint was cardiovascular death, myocardial infarction, stroke, angina requiring coronary revascularization, or peripheral arterial disease requiring surgery or peripheral arterial intervention. Results At 3 years, Kaplan–Meier estimated cumulative incidence of the primary endpoint was 2.5% (95% confidence interval, 2.1%–2.9%) in O3AEE-treated patients (N = 6,580) and 2.7% (2.4%–3.1%) in non-O3AEE-treated patients (N = 7,784; hazard ratio, 0.99; 95% confidence interval, 0.79–1.23). Incidence of heart failure requiring hospitalization was 0.4% with O3AEE versus 0.8% in non-O3AEE-treated patients (hazard ratio, 0.47; 95% confidence interval, 0.28–0.78; P<0.05). Conclusions Among patients receiving statins, cardiovascular event incidence did not differ significantly between O3AEE-treated patients and non-O3AEE-treated patients. Further studies are required before definitive conclusions can be drawn on the effect of O3AEE on cardiovascular event incidence in high-risk patients with hypertriglyceridemia. Trial registration ClinicalTrials.gov, NCT02285166.

Breast cancer-related lymphedema (BCRL) is a common complication of axillary lymph node dissection (ALND) but can also develop after sentinel lymph node biopsy (SLNB). Several models have been developed to predict the risk of disease development before and after surgery; however, these models have shortcomings that include the omission of race, inclusion of variables that are not readily available to patients, low sensitivity or specificity, and lack of risk assessment for patients treated with SLNB. To create simple and accurate prediction models for BCRL that can be used to estimate preoperative or postoperative risk. In this prognostic study, women with breast cancer who underwent ALND or SLNB from 1999 to 2020 at Memorial Sloan Kettering Cancer Center and the Mayo Clinic were included. Data were analyzed from September to December 2022. Diagnosis of lymphedema based on measurements. Two predictive models were formulated via logistic regression: a preoperative model (model 1) and a postoperative model (model 2). Model 1 was externally validated using a cohort of 34 438 patients with an International Classification of Diseases diagnosis of breast cancer. Of 1882 included patients, all were female, and the mean (SD) age was 55.6 (12.2) years; 80 patients (4.3%) were Asian, 190 (10.1%) were Black, 1558 (82.8%) were White, and 54 (2.9%) were another race (including American Indian and Alaska Native, other race, patient refused to disclose, or unknown). A total of 218 patients (11.6%) were diagnosed with BCRL at a mean (SD) follow-up of 3.9 (1.8) years. The BCRL rate was significantly higher among Black women (42 of 190 [22.1%]) compared with all other races (Asian, 10 of 80 [12.5%]; White, 158 of 1558 [10.1%]; other race, 8 of 54 [14.8%]; P < .001). Model 1 included age, weight, height, race, ALND/SLNB status, any radiation therapy, and any chemotherapy. Model 2 included age, weight, race, ALND/SLNB status, any chemotherapy, and patient-reported arm swelling. Accuracy was 73.0% for model 1 (sensitivity, 76.6%; specificity, 72.5%; area under the receiver operating characteristic curve [AUC], 0.78; 95% CI, 0.75-0.81) at a cutoff of 0.18, and accuracy was 81.1% for model 2 (sensitivity, 78.0%; specificity, 81.5%; AUC, 0.86; 95% CI, 0.83-0.88) at a cutoff of 0.10. Both models demonstrated high AUCs on external (model 1: 0.75; 95% CI, 0.74-0.76) or internal (model 2: 0.82; 95% CI, 0.79-0.85) validation. In this study, preoperative and postoperative prediction models for BCRL were highly accurate and clinically relevant tools comprised of accessible inputs and underscored the effects of racial differences on BCRL risk. The preoperative model identified high-risk patients who require close monitoring or preventative measures. The postoperative model can be used for screening of high-risk patients, thus decreasing the need for frequent clinic visits and arm volume measurements.

PCN274 MONITORING WITH BIOIMPEDANCE SPECTROSCOPY TO REDUCE THE RATE OF PROGRESSION TO CHRONIC BREAST CANCER RELATED LYMPHEDEMA: A META-ANALYSIS

There is little research on hand edema in the population at risk for breast cancer-related lymphedema (BCRL). Study aims included reporting potential importance of hand edema (HE) as a risk factor for progression of edema in patients treated for breast cancer at risk for BCRL, reporting risk factors for BCRL, and reporting treatment of HE. This was a retrospective analysis of 9 patients treated for breast cancer in Massachusetts General Hospital's lymphedema screening program who presented with isolated HE. Limb volumes via perometry, BCRL risk factors, and HE treatment are reported. Edema was mostly isolated to the hand. Three patients had arm edema >5% on perometry; and 2 of these had edema outside the hand on clinical examination. Patients were at high risk of BCRL with an average of 2.9/5 known risk factors. Arm edema progressed to >10% in 2 high-risk patients. Treatment resulted in an average hand volume reduction of 10.2% via perometry and improvement upon clinical examination. The small sample size and lack of validated measures of subjective data were limitations. In this cohort, patients with HE carried significant risk factors for BCRL. Two out of 9 (22%), both carrying ≥4/5 risk factors, progressed to edema >10%. Isolated HE may be a prognostic factor for edema progression in patients treated for breast cancer at risk for BCRL. Further research is warranted.

Breast cancer-related lymphedema (BCRL) can have a significant impact on breast cancer survivors quality of life. The purpose of this review is to evaluate diagnostic tools for the assessment of BCRL. Multiple BCRL diagnostic tools are available, though older diagnostic tools have low sensitivity, limiting the ability for sub-clinical BCRL diagnosis while BIS and perometry have increased sensitivity and theability to diagnose BCRL sub-clinically. Prospective studies have demonstrated such an approach coupled to early intervention is associated with low rates of chronic BCRLwhile a recently published randomized trial demonstrated that prospective surveillance with BIS coupled with early intervention reduced rates of chronic BCRL as compared to circumference measurements with compression garments. Prospective and randomized data support the use of prospective surveillance for BCRL. The strongest data available comes from the PREVENT trial and supports prospective BCRL surveillance with bioimpedance spectroscopy coupled to early intervention with a compression sleeve.

Background: Breast cancer related lymphedema (BCRL) represents a dreaded complication of breast cancer treatment that can lead to morbidity, diminished quality of life, and psychosocial harm and is associated with increased costs. Increasingly, data has supported the concept of prospective BCRL surveillance coupled with early intervention to mitigate these effects. Methods: We performed a systematic review of the literature searching for published randomized and prospective data evaluating prospective BCRL surveillance with early intervention. Results: We identified 12 studies (2,907 patients) including 4 randomized trials (1,203 patients) and 8 prospective studies (1,704 patients). Randomized data consistently demonstrate that early intervention reduces rates of progression to chronic BCRL with multiple paradigms and diagnostic modalities utilized; the strongest data in the review comes from the randomized PREVENT trial which demonstrated early detection with bioimpedance spectroscopy (BIS), coupled with a compression garment applied for 12 hours a day over 4 weeks, significantly reduced the rate of chronic BCRL compared to tape measurement. Conclusions: Current data support the role of prospective BCRL surveillance with early detection and intervention to reduce rates of chronic BCRL. Breast cancer patients at risk for BCRL should undergo prospective surveillance as part of survivorship. Given the level 1 data demonstrating that BIS is superior to conventional tape measure, it should be included as the standard BCRL diagnostic modality unless an equally effective modality is employed. Citation Format: Pat Whitworth, Frank Vicini, Stephanie Valente, Kirstyn Brownson, Beth Dupree, Manpreet Kohli, Laura Lawson, Chirag Shah. Reducing Rates of Chronic Breast Cancer Related Lymphedema with Screening &amp; Early Intervention: An Update of Recent Data [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-08-15.

BackgroundDelirium in patients with hip fractures lead to higher morbidity and mortality. Prevention in high-risk patients by prescribing low dose haloperidol is currently under investigation.MethodsThis prospective cohort surveillance assessed hip fracture patients for risk of developing a delirium with the Risk Model for Delirium (RD) score. High-risk patients (score ≥ 5 points) were treated with a prophylactic low-dose of haloperidol according to hospital protocol. Primary outcome was delirium incidence. Secondary outcomes were differences between high- and low-risk patients in delirium, length of stay (LOS), return to pre-fracture living situation and mortality. Logistic regression analysis was performed with age, ASA-classification, known dementia, having a partner, type of fracture, institutional residence and psychotropic drug use as possible confounders.Results445 hip fracture patients aged 65 years and older were admitted from January 2008 to December 2009. The RD-score was completed in 378 patients, 173 (45.8%) high-risk patients were treated with prophylactic medication. Sensitivity was 71.6%, specificity 63.8% and the negative predictive value (NPV) of a score < 5 was 85.9%.Delirium incidence (27.0%) was not significantly different compared to 2007 (27.8%) 2006 (23.9%) and 2005 (29.0%) prior to implementation of the RD- protocol.Logistic regression analysis showed that high-risk patients did have a significant higher delirium incidence (42.2% vs. 14.1%, OR 4.1, CI 2.43-7.02). They were more likely to be residing at an alternative living situation after 3 months (62.3% vs. 17.0%, OR 6.57, CI 3.23-13.37) and less likely to be discharged from hospital before 10 days (34.9% vs. 55.9%, OR 1.63, CI 1.03-2.59). Significant independent risk factors for a delirium were a RD-score ≥ 5 (OR 4.13, CI 2.43-7.02), male gender (OR 1.93, CI 0.99-1.07) and age (OR 1.03, CI 0.99-1.07).ConclusionsIntroducing the delirium prevention protocol did not reduce delirium incidence.The RD-score did identify patients with a high risk to develop a delirium. This high-risk group had a longer LOS and returned to pre-fracture living situation less often.The NPV of a score < 5 was high, as it should be for a screening instrument. Concluding, the RD-score is a useful tool to identify patients with poorer outcome.