Arm Lymphedema Research Articles

Quantifying Risk of Ipsilateral Arm Lymphedema Causing Functional Impairment in Breast Cancer Patients: Results From a Prospective, Multi-Centre International Study of Treatment Toxicity

Breast cancer related lymphedema (BCRL) of the ipsilateral arm remains a highly morbid long-term side effect of breast cancer treatment, one which can lead to functional impairment. We sought to independently examine clinical and treatment related risk factors for the development of lymphedema-associated functional impairment.The REQUITE Consortium is a multi-center cohort study of patients with breast cancer treated at 26 hospitals in 8 countries from 2014-2017 who were prospectively evaluated for treatment toxicity. All patients received lumpectomy and adjuvant radiotherapy (RT) with or without chemotherapy at the discretion of their treating physician, and were enrolled prior to beginning RT. Arm circumference measurements and patient reported outcome (PRO) toxicity assessments were obtained before RT and annually after RT for a minimum of two years. Lymphedema-associated functional impairment was determined by PRO lymphedema that constrains activity and self-care. Grade 2+ BCRL was defined as ≥10% discrepancy in ipsilateral arm circumference compared to the contralateral arm. Cumulative incidence curves were stratified by the extent of axillary surgery and RT. Multivariable Cox models adjusted for axillary surgery, radiation, body mass index, and chemotherapy.The cohort included 1921 patients followed for a median of 27 months: 1345 received sentinel node biopsy (SLNBx) alone, 90 received SLNBx and regional lymph node RT (RLNR), 136 received axillary node dissection (ALND) alone, 200 received ALND+RLNR, and 150 received no axillary treatment. Invasive breast cancer was present in 1678 (87%) patients, while 591 (30.7%) received chemotherapy. Among the whole cohort, four times as many patients reported functional impairment than Grade 2+ BCRL (4.6% vs 1.1%). On multivariable analysis, taxane-based chemotherapy resulted in a significantly higher risk of functional impairment (hazard ratio [HR] 1.90, P = 0.01), as did ALND (HR 11.92, P = 0.02) and higher BMI (HR 1.06, P < 0.001). Although RLNR and SLNBx did not confer significantly higher risk on multivariable analysis when evaluated individually, the SLNBx+RLNR treatment group demonstrated a trend towards significantly higher risk of functional impairment compared to no axillary treatment (HR 8.21, P = 0.05). The risk of functional impairment was highest in those receiving ALND+RLNR (HR 15.52, P = 0.008) and ALND alone (HR 14.58, P = 0.01), with a 3-year cumulative incidence rate of 21% in both groups.Patients treated with taxane-based chemotherapy and those receiving more extensive axillary surgery are at significantly higher risk of developing ipsilateral arm lymphedema causing functional impairment. Additional variation in this toxicity may be due to genetic predisposition, which is under investigation in REQUITE. Lymphedema-associated functional impairment occurred substantially more often than Grade 2+ BCRL, highlighting the importance of capturing PROs.

A Pilot Study to Quantify Breast Lymphedema for Patients Undergoing Breast Conserving Therapy (BCT) for Breast Cancer

<h3>Purpose/Objective(s)</h3> Upper extremity lymphedema after axillary lymph node dissection and radiation for breast cancer has been well described and studied. As modern treatment techniques have reduced the incidence of arm lymphedema, breast lymphedema has emerged as a common result of BCT and is associated with poor wound healing, infection and impact on quality of life. Because there is no established tool for its evaluation and quantification, we explored the feasibility of using ultrasound to measure breast lymphedema objectively. We evaluated whether this measure correlated with clinical assessment, treatment factors, and patient-reported outcomes. <h3>Materials/Methods</h3> We enrolled 30 women with malignant breast cancer treated with breast conserving surgery, sentinel lymph node biopsy, and breast radiation. Another 10 women with benign disease who had not undergone BCT were sampled as controls. Ultrasound measurements of dermal thickness were performed on the treated breast and untreated breast at the 6:00 position. Post-treatment assessments included physical exam and quality of life DASH questionnaire. We quantified breast lymphedema as the dermal thickness of the affected breast minus the dermal thickness of the unaffected breast. Breast lymphedema was considered present if dermal thickness difference was above the highest-observed value in the benign patients. <h3>Results</h3> Mean age (± SD) was SD 59 ± 13 in the malignant group and 46.4 ± 17 in the benign group and groups were similar with regard to body mass index. Mean dermal thickness difference was higher in the malignant group compared with the benign group (1.03 mm and 0 mm, respectively). Seventy percent of patients in the malignant group met our definition of breast lymphedema (n = 21) and were more likely to report impact on quality of life pertaining to sexual activity (24% vs 11%), breast sensation (52% vs 16%), sleep quality (33% vs 21%) and confidence (24% vs 5%) than patients without breast lymphedema. Extent of axillary surgery was associated with a 1.29 mm increase in difference in dermal thickness for patients with > = 4 nodes removed (95% CI: -0.22, 2.80). The volume of breast tissue radiated was also positively associated, with every 100cc increase in breast volume radiated associated with a 0.17mm greater dermal thickness difference (95% CI: 0.04, 0.30mm). However, there was no association with percent of breast tissue receiving > 105% of prescribed dose (95% CI: -0.07, 0.01), hypofractionation vs. standard fractionation (95% CI: -1.2, 0.68) or total radiation dose (95% CI: -0.5, 1.2). <h3>Conclusion</h3> Breast lymphedema is an impactful sequela of breast cancer treatment but remains understudied with no standard measurement tools. Our pilot study demonstrates that ultrasound is a promising tool for the characterization of breast lymphedema and may improve our understanding of patient and modifiable treatment risk factors.

Six-Month Follow-up for Investigating the Effect of Prophylactic Lymphovenous Anastomosis on the Prevention of Breast Cancer-Related Lymphedema: A Preliminary Study in a Single Institution

Purpose: This study was performed to assess the effect of prophylactic lymphovenous anastomosis on the prevention of arm lymphedema after axillary lymph node dissection for breast cancer treatment.Methods: Among 69 women referred to undergo axillary lymph node dissection from January 2020 to June 2020, 21 were assigned to the treatment group and 48 to the control group. In the treatment group, 21 patients underwent prophylactic lymphovenous anastomosis for the prevention of breast cancer-related lymphedema. The other 48 patients in the control group did not undergo any preventive surgical treatment. Prophylactic lymphovenous anastomosis was performed at the same time as axillary lymph node dissection and breast cancer surgery. Postoperatively, all patients underwent circumferential measurements at 1, 3, and 6 months and lymphography at 6 months after the surgery. Results: None of the patients in the treatment group had lymphedema after the surgery (0%). In the control group, lymphedema occurred in nine patients (18.8%, p=0.049). No significant differences in the arm circumference were observed in the treatment group during follow-up (p&gt;0.05), whereas the arm circumference in the control group showed a significant increase at 1, 3, and 6 months after axillary lymph node dissection (p&lt;0.05). There were no significant differences between the two groups in the arm circumference changes with respect to baseline at 1, 3, and 6 months after axillary lymph node dissection (p&gt;0.05). Conclusion: Prophylactic lymphovenous anastomosis represents a valid super microsurgical technique for the primary prevention of breast cancer-related lymphedema.

Development and Clinical Validation of the LymphMonitor Technology to Quantitatively Assess Lymphatic Function.

Current diagnostic methods for evaluating the functionality of the lymphatic vascular system usually do not provide quantitative data and suffer from many limitations including high costs, complexity, and the need to perform them in hospital settings. In this work, we present a quantitative, simple outpatient technology named LymphMonitor to quantitatively assess lymphatic function. This method is based on the painless injection of the lymphatic-specific near-infrared fluorescent tracer indocyanine green complexed with human serum albumin, using MicronJet600TM microneedles, and monitoring the disappearance of the fluorescence signal at the injection site over time using a portable detection device named LymphMeter. This technology was investigated in 10 patients with unilateral leg or arm lymphedema. After injection of a tracer solution into each limb, the signal was measured over 3 h and the area under the normalized clearance curve was calculated to quantify the lymphatic function. A statistically significant difference in lymphatic clearance in the healthy versus the lymphedema extremities was found, based on the obtained area under curves of the normalized clearance curves. This study provides the first evidence that the LymphMonitor technology has the potential to diagnose and monitor the lymphatic function in patients.

Advanced translation and cultural adaption of the LYMPH-Q Upper Extremity Module from English to Danish

BackgroundTo better quantify the impact that breast cancer-related arm lymphedema (BCRL) has on health-related quality of life (HR-QOL), a disease-specific patient-reported outcome measure (PROM) is needed. The LYMPH-Q Upper Extremity Module was recently developed for patients with BCRL. The aim of this study was to perform an advanced translation and culturally adapt the LYMPH-Q Upper Extremity Module for use in Denmark.MethodsThe LYMPH-Q Upper Extremity Module was translated into Danish according to the guidelines of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) and the World Health Organization (WHO). The process included two forward and one back translation, an expert panel meeting, and cognitive debriefing interviews with patients. The focus of the translation was to develop a Danish version that used appropriate patient-friendly language while maintaining the meaning of the items, instructions and response options.ResultsThe two forward translations resulted in minor differences in terminology. These discrepancies were discussed among the translators and a harmonized Danish version 1 was achieved. Comparison of the back translation to the original English version identified 14 items/instructions/response options that required re-translation. Subsequently, experts helped to identify and resolve the language for 10 items/instructions/response options that did not maintain the same meaning as the English version. Participants in the cognitive debriefing interviews did not report any difficulties with understanding the items/instructions/response options.ConclusionsThe translation and cultural adaption process led to the development of a conceptually equivalent Danish version of the LYMPH-Q Upper Extremity Module.Level of Evidence: Not gradable

Nighttime compression supports improved self-management of breast cancer-related lymphedema: A multicenter randomized controlled trial.

Lymphedema is a prevalent long-term effect of breast cancer treatment associated with reduced quality of life. This study examined the efficacy of nighttime compression as a self-management strategy for women with chronic breast cancer-related lymphedema. Th authors conducted a parallel 3-arm, multicenter, randomized trial. Women were recruited from 3 centers in Canada and randomized to group 1 (daytime compression garment alone [standard care]), group 2 (daytime compression garment plus nighttime compression bandaging), or group 3 (daytime compression garment plus the use of a nighttime compression system garment). The primary outcome was the change in excess arm volume from the baseline to 12weeks. Participants from all groups used a nighttime compression system garment from weeks 13 to 24. One hundred twenty women were enrolled, 118 completed the randomized trial, and 114 completed the 24-week follow-up. The rates of adherence to nighttime compression were 95%±15% and 96%±11% in the compression bandaging and nighttime compression system groups, respectively. After the intervention, the addition of nighttime compression was found to be superior to standard care for both absolute milliliter reductions (P=.006) and percentage reductions (P=.002) in excess arm lymphedema volume. Significant within-group changes were seen for quality of life across all groups; however, no between-group differences were found (P>.05). The trial demonstrated a significant improvement in arm lymphedema volume from the addition of nighttime compression whether through the application of compression bandaging or through the use of a nighttime compression system garment. Lymphedema is swelling that occurs in the arm on the side of the surgery for breast cancer. Lymphedema occurs in approximately 21% of women. Lymphedema tends to worsen over time and can result in recurrent infections in the arm, functional impairment, and pain. Currently, treatment consists of intensive treatments to reduce the swelling followed by regular use of a compression sleeve during the day. This study examined and found a benefit from the addition of nighttime compression (whether through self-applied compression bandaging or through the use of a nighttime compression system garment) to the use of a daytime compression sleeve.

Hypofractionated Radiation Therapy (HFRT) of Breast/Chest Wall and Regional Nodes in Locally Advanced Breast Cancer: Toxicity Profile and Survival Outcomes in Retrospective Monoistitutional Study

AIMTo evaluate the efficacy and safety of hypofractionated radiation therapy (HFRT) of the breast/chest wall and regional nodes in patients with locally advanced breast cancer and positive lymph nodes. Materials and MethodsOne hundred and twenty-two patients treated between October 2016 and March 2020 with HFRT were retrospectively reviewed. A total dose of 42.4 Gy was delivered to the chest wall and lymph nodes in 16 fractions of 2.65 Gy each, using the IMRT technique. Patients treated with breast-conserving surgery received an overdose (concomitant boost of 3 Gy daily) with the SIB (Simultaneous Integrated Boost) technique. ResultsMedian age at diagnosis was 58 years (range 34-86 years) and median follow-up was 22 months (range 6-48 months). Overall survival (OS) at 1, 2 and 3 years was 100%, 97.3% and 90%, respectively. Disease-free survival (DFS) at 1, 2, and 3 years was 91.4%, 87%, and 84.8%, respectively. Distant metastasis-free survival (MFS) at 1, 2 and 3 years was 93.1%, 88% and 85.7%, respectively. Two patients (1.6%) experienced local recurrence on the chest wall during FUP. Twenty-one patients (17%) showed a grade 2 dermal toxicity, no grade 3 acute skin toxicity was found. Sixteen patients (13%) showed early-stage arm lymphedema (grade ≤ 2). Twenty-three patients (19%) showed a grade 2 late skin toxicity. Twenty patients (16%) had grade ≤ 2 late arm lymphedema. ConclusionGiven the excellent local control, survival rates and the low toxicity profile demonstrated, HFRT could be considered a valid therapeutic option in patients with locally advanced breast cancer.

Tissue Dielectric Constant and Water Displacement Method Can Detect Changes of Mild Breast Cancer-Related Arm Lymphedema.

Background: Most commonly, volume measurements are used to evaluate the effect of lymphedema treatment, but as the accumulation of lymph fluid can be local, this method may not always be the best. Tissue dielectric constant (TDC) can be applied to identify local lymphedema changes, but has not been used before when evaluating treatment in mild arm lymphedema. Thus, the overall aim of this study was to examine if TDC and water displacement method (WDM) can measure changes in mild breast cancer-related lymphedema during the 6-month standard treatment. More specifically, we examined changes within and between three defined groups based on lymphedema thresholds of TDC and WDM at start of treatment, as well as changes of the highest TDC ratio and site. Methods and Results: Forty-six women with mild arm lymphedema, received treatment with compression sleeves, mostly ccl 1, and instructions about self-care. Local tissue water was measured by TDC at six defined sites and lymphedema relative volume (LRV) by WDM before treatment and at first, second, third, and sixth month. There was a significant decrease in the site with the highest TDC ratio, as well as LRV at all follow-up visits. At 6 months, TDC ratio had decreased mean 0.26 (p < 0.001) and LRV mean - 3.3% (p < 0.001). There was a significant difference between the groups in change of TDC ratio, but not in LRV. Sixty percent changed the overall highest TDC ratio to another site during 6 months. Conclusion: Both TDC and WDM could detect changes in mild arm lymphedema but should be interpreted separately.

Long-Term Results of Postoperative Hypofractionated Accelerated Breast and Lymph Node Radiotherapy (HypoAR) with Hypofractionated Boost.

We report long-term results (median follow-up 12 years) of hypofractionated accelerated radiotherapy (HypoAR) in patients treated with breast-conserving surgery. In total, 367 women were treated with HypoAR. Axillary and supraclavicular area (ASA) were treated in patients with involved nodes. In total, 290 patients (scheme A) received 3.5 Gy/day ×10 fractions (breast/ASA) followed by two 4 Gy fractions with electrons to the affected breast quadrant within 16 days. In total, 77 patients (Scheme B) received 2.7 Gy/day for 16 consecutive fractions (breast/ASA) within 22 days, while concurrently, the affected breast quadrant received an electron booster dose of 0.8 Gy for the first 13 fractions. Amifostine was offered to 252/367 patients. Early radiation toxicity was minimal. Regarding late toxicities, symptomatic breast edema was noted in 2.2%, asymptomatic breast fibrosis in 1.9%, and arm lymphedema in 3.7% of patients. Amifostine reduced early radiation dermatitis (p = 0.001). In total, 2.2% of patients developed contralateral breast and 1.6% other carcinomas. Locoregional recurrence (LR) occurred in 3.1% of patients (0% for in situ carcinomas). Positive margins after surgery, extracapsular node invasion, and HER2-enriched/triple-negative tumors were linked with significantly worse LR-free survival. The involvement of more than three nodes and luminal type other than A were independent prognostic variables of metastasis and death events. HypoAR delivering a biological dose of 50–52 Gy to the breast/ASA is a safe and effective therapy for patients treated with conservative surgery. The risk of carcinogenesis is low. Positive surgical margins, extracapsular node invasion, and HER2-enriched/triple-negative phenotypes appear as a cluster of features linked with a higher risk for locoregional relapse.

Functional axillary dissection based on lymphatic drainage for breast cancer: a single center randomized clinical trial

Objective: To evaluate the effectiveness and safety of functional axillary dissection based on lymphatic drainage (FUND) in decreasing breast cancer-related lymphedema (BCRL) events. Methods: A total of 168 eligible patients in Zhongnan Hospital of Wuhan University from July 2018 to February 2019 were randomly assigned to the FUND group or axillary lymph node dissection (ALND) group using random number table generated by SPSS. In the FUND group, methylene blue (MB) was adopted to reveal the sentinel lymph node (SLN) for all patients; 0.1 ml MB was injected into the SLNs before resection to reveal the efferent lymphatic channels and subsequent-echelon lymph node. The blue-stained lymphatic channels were mapped by bluntly dissecting along the lymphatic drainage channels from the breast to the axilla. Then, the SLNs were removed and pathologically analyzed by immediate frozen sectioning (FS); if the SLNs were positive, the blue-stained bALNs in breast lymphatic level (BLL) Ⅱ were removed and sent for immediate FS; if the blue-stained ALNs in BLL Ⅱ were confirmed negative, the tissues in BLL Ⅱ were removed'en bloc'. Clinicopathologic information for all the patients in the two groups were collected. The fixed-point circumference volume measurement method and the Norman questionnaire scoring method were used to evaluate the arm lymphedema between the two groups. Clinicopathological characteristics, incidences of arm lymphedema, locoregional recurrence, and distant metastasis between the two groups were compared. Results: The mean age were (50.3±8.0) in the FUND group and (51.1±9.0) in the ALND group. Seventy-four cases (88.1%) in the FUND group successfully underwent FUND surgery, and patients whose breast lymphatics failed to be stained blue underwent standard ALND. There was no statistically significant difference in terms of age, BMI, histological types, surgical approaches and adjunct therapy between the FUND group (n=74) and ALND group (n=84) (P>0.05). The average operation time of the FUND group and the stand ALND group were (169±15) and (123±12) min respectively (range: 145-198, 103-146 min) (P<0.001), and the number of lymph nodes removed [M (Q1, Q3)] were 8.3 (6, 15) and 12.9 (7, 18) (P=0.019). The cumulative BCRL rate, within a median follow-up of 24 months and 23 months respectively for FUND and ALND group, were 10.8% (8/74) vs 23.8% (20/84) (P=0.033) measured by fixed-point circumference volume measurement method, and was 12.2% (9/74) vs 27.4% (23/84) by Norman questionnaire (P=0.018). There were no local regional recurrence events during the follow-up period between the two groups. Conclusion: For breast cancer patients with clinically node-positive axilla or positive SLN, FUND based on lymphatic drainage was a less radical axillary surgery, with which eliminating the risk of BCRL might be achieved.

The prevalence of arm lymphedema after radiation treatment in patients with breast cancer

AbstractAim:To evaluate the prevalence and risk factors of arm lymphedema in patients with breast cancer.Materials and methods:Between 2006 and 2017, we investigated patients with breast cancer after breast surgery who received adjuvant radiotherapy at the breast or chest wall, and/or adjuvant radiotherapy at regional lymph nodes, and standard systemic chemotherapy depending on disease stage and risk factors. We assessed arm lymphedema using arm circumference measurement differences on the treated side compared with the opposite arm (≥2 cm measurements at any one position). Associations between arm lymphedema and potential risk factors were identified using statistical analysis.Results:In 308 patients, arm lymphedema prevalence was 6·2%. Patients having ≥20 lymph nodes removed (hazard ratio (HR) = 3·29; 95% confidence interval (CI): 1·12–8·87), undergoing regional lymph node irradiation (HR = 1·81; 95% CI: 1·09–13·28), and no arm and shoulder exercises after treatment (HR = 3·16; 95% CI: 1·89–5·26) had a higher risk of arm lymphedema.Findings:Arm lymphedema is a serious breast cancer complication and is a preventable morbidity. Planning arm and shoulder exercises in line with adjuvant treatments and increasing clinical awareness of early indications could help lower the risk of occurrence.

Evolutionary ensemble feature selection learning for image‐based assessment of lymphedema arm volume

SummaryArm lymphedema is a side effect of surgery and radiation therapy in patients with breast cancer. There are several methods to measure lymphedema arm volume, such as water displacement (WD) and circumferential measurement (CM). Although these techniques have a satisfactory level of accuracy, they have some limitations for clinical use in practical applications. To overcome these drawbacks, a horizontal‐vertical image scanning (HVIS) tool, is presented as a valid method for arm volume measurement. To predict the arm volume, an evolutionary ensemble feature selection learning (named EEFSL) comprising different base learners (KNN, SVM, ANFIS, Decision Tree, and Naïve Bayes) is presented. In order to improve the performance of the EEFSL model, its hyperparameters are optimized using genetic algorithm (GA). The hyperparameters include the weights of different base learners and the specific features for each base learner. The fitness function of GA is to maximize the correlation between predicted and actual arm volumes. The proposed method was successfully developed for arm measurement of 60 arms from 30 women with arm lymphedema. Obtained results indicate that the proposed HVIS‐EEFSL method is a reliable and valid technique to measure arm volume of patients with lymphedema, suitable for daily clinical use instead of WD and CM.

Dantrolene Prevents the Lymphostasis Caused by Doxorubicin in the Rat Mesenteric Circulation.

Background and Purpose: Doxorubicin (DOX) is a risk factor for arm lymphedema in breast cancer patients. We reported that DOX opens ryanodine receptors (RYRs) to enact “calcium leak,” which disrupts the rhythmic contractions of lymph vessels (LVs) to attenuate lymph flow. Here, we evaluated whether dantrolene, a clinically available RYR1 subtype antagonist, prevents the detrimental effects of DOX on lymphatic function.Experimental Approach: Isolated rat mesenteric LVs were cannulated, pressurized (4–5 mm Hg) and equilibrated in physiological salt solution and Fura-2AM. Video microscopy recorded changes in diameter and Fura-2AM fluorescence tracked cytosolic free calcium ([Ca2+ i]). High-speed in vivo microscopy assessed mesenteric lymph flow in anesthetized rats. Flow cytometry evaluated RYR1 expression in freshly isolated mesenteric lymphatic muscle cells (LMCs).Key Results: DOX (10 μmol/L) increased resting [Ca2+ i] by 17.5 ± 3.7% in isolated LVs (n = 11). The rise in [Ca2+ i] was prevented by dantrolene (3 μmol/L; n = 10). A single rapid infusion of DOX (10 mg/kg i.v.) reduced positive volumetric lymph flow to 29.7 ± 10.8% (n = 7) of baseline in mesenteric LVs in vivo. In contrast, flow in LVs superfused with dantrolene (10 μmol/L) only decreased to 76.3 ± 14.0% (n = 7) of baseline in response to DOX infusion. Subsequently, expression of the RYR1 subtype protein as the presumed dantrolene binding site was confirm in isolated mesenteric LMCs by flow cytometry.Conclusion and Implications: We conclude that dantrolene attenuates the acute impairment of lymph flow by DOX and suggest that its prophylactic use in patients subjected to DOX chemotherapy may lower lymphedema risk.

Stepwise Limited Axillary Lymph Node Dissection Based on Lymphatic Drainage from the Breast to Decrease Breast Cancer-Related Lymphedema: A Randomized Controlled Trial.

Comprehensive axillary surgery is associated with an elevated rate of morbidity. This trial aimed to demonstrate the feasibility of axillary dissection of lymph nodes from the breast (bALND) for the purpose of limiting the extent of surgery. Patients enrolled from two tertiary referral centers from September 2018 to September 2019 were randomly allocated to two groups: bALND and standard axillary lymph node dissection (sALND). In the bALND group, the sentinel lymph node was filled with 0.1 ml methylene blue before resection. Then, bALND based on lymphatic drainage was subsequently performed. Lymph nodes at each breast lymphatic level and lymph nodes at Berg levels were sent for separate pathological examination. Arm lymphedema, locoregional recurrence, and distant metastasis were documented. In the bALND group, lymphatic vessels and subsequent-echelon lymph nodes from the breast were stained blue after injection of methylene blue in 404 (89.0%, 404/454) cases, and 57.8% (228/394) of the patients harbored fewer than four metastatic nodes. With a median follow-up of 18 months, the incidence of arm lymphedema was 6.6% (26/394) in the bALND group versus 13.7% (60/438) in the sALND group (p = 0.008), while regional recurrence presented no difference between the two surgical procedures (0.76% vs 0.68%, p = 0.896). For node-positive breast cancer patients, bALND based on lymphatic drainage is a less radical axillary surgery that can eliminate morbidity without impairing cancer control.

Adipocytes are larger in lymphedematous extremities than in controls

Lymphedema is caused by dysfunctional lymph vessels or as a complication of cancer treatment leading to edema and adipose tissue deposition. One hypothesis is that adipocyte hypertrophy contributes to the volume increase in lymphedema. The aim of the study was to compare adipocyte size in arm and leg lymphedema and controls. The adipocyte size difference was also compared between the arms and legs. Furthermore, any link between adipocyte size difference and gender, lymphedema onset, duration, previous radio- and chemotherapy was studied, as well as any relationship to total excess volume increase in the extremities, body mass index (BMI) and body weight. Adipose tissue biopsies from the lymphedematous and non-affected extremities were taken from 47 patients. The adipocytes sizes were measured using an Olympus PROVIS microscope, Olympus DP50 camera (Olympus, Tokyo, Japan) and ImageJ program (NIH, Bethesda, MD). Additional information was obtained from the Lymphedema Center database. The data were assembled in Excel and statistics was calculated in SPSS® Statistics 23 (IBM®, Armonk, NY). The adipocyte size (mean ± SEM) in the lymphedematous extremities was significantly larger, 8880 ± 291 μm2, compared to the adipocyte size in the non-affected extremities, where it was 7143 ± 280 μm2, i.e. 24% larger (p < .001). The adipocyte size increase was larger in arm than in leg lymphedema. No correlation was found between adipocyte size and gender or onset. However, a negative correlation was found between adipocyte size difference and duration. No correlation was found between adipocyte size and previous chemo- or radiotherapy. There was a positive correlation between adipocyte size and BMI. Hypertrophy of adipocytes was seen in the lymphedematous extremities versus control and contributes to the excess volume.

Weight loss does not decrease risk of breast cancer-related arm lymphedema.

The goal of this study was to determine the relationship between postoperative weight change and breast cancer-related lymphedema (BCRL). In this cohort study, 1161 women underwent unilateral breast surgery for breast cancer from 2005 to 2020 and were prospectively screened for BCRL. Arm volume measurements were obtained via an optoelectronic perometer preoperatively, postoperatively, and in the follow-up setting every 6 to 12 months. Mean follow-up from preoperative baseline was 49.1 months. The main outcome was BCRL, defined as a relative volume change of the ipsilateral arm of ≥10% at least 3 months after surgery. A total of 92 patients (7.9%) developed BCRL. Net weight loss versus net weight gain from baseline to last follow-up was not protective against developing BCRL (hazard ratio, 1.38; 95% confidence interval, 0.89-2.13; P = .152). Although weight loss may be recommended as part of an individualized lifestyle management program for overall health, weight loss alone may not decrease the risk of developing BCRL.

Assessment of Potential Risk Factors and Skin Ultrasound Presentation Associated with Breast Cancer-Related Lymphedema in Long-Term Breast Cancer Survivors.

Breast cancer has been reported to have the highest survival rate among various cancers. However, breast cancer survivors face several challenges following breast cancer treatment including breast cancer-related lymphedema (BCRL), sexual dysfunction, and psychological distress. This study aimed to investigate the potential risk factors of BCRL in long term breast cancer survivors. A total of 160 female breast cancer subjects were recruited on a voluntary basis and arm lymphedema was assessed through self-reporting of diagnosis, arm circumference measurement, and ultrasound examination. A total of 33/160 or 20.5% of the women developed BCRL with significantly higher scores for upper extremity disability (37.14 ± 18.90 vs. 20.08 ± 15.29, p < 0.001) and a lower score for quality of life (103.91 ± 21.80 vs. 115.49 ± 16.80, p = 0.009) as compared to non-lymphedema cases. Univariate analysis revealed that multiple surgeries (OR = 5.70, 95% CI: 1.21–26.8, p < 0.001), axillary lymph nodes excision (>10) (OR = 2.83, 95% CI: 0.94–8.11, p = 0.047), being overweight (≥25 kg/m2) (OR = 2.57, 95% CI: 1.04 – 6.38, p = 0.036), received fewer post-surgery rehabilitation treatment (OR = 2.37, 95% CI: 1.05–5.39, p = 0.036) and hypertension (OR = 2.38, 95% CI: 1.01–5.62, p = 0.043) were associated with an increased risk of BCRL. Meanwhile, multivariate analysis showed that multiple surgeries remained significant and elevated the likelihood of BCRL (OR = 5.83, 95% CI: 1.14–29.78, p = 0.034). Arm swelling was more prominent in the forearm area demonstrated by the highest difference of arm circumference measurement when compared to the upper arm (2.07 ± 2.48 vs. 1.34 ± 1.91 cm, p < 0.001). The total of skinfold thickness of the affected forearm was also significantly higher than the unaffected arms (p < 0.05) as evidenced by the ultrasound examination. The continuous search for risk factors in specific populations may facilitate the development of a standardized method to reduce the occurrence of BCRL and provide better management for breast cancer patients.

Cellulitis Is Associated with Severe Breast Cancer-Related Lymphedema: An Observational Study of Tissue Composition.

Simple SummaryCellulitis is a common complication in Breast Cancer-Related Lymphedema (BCRL); however, it is not known whether cellulitis is associated with the severity and biocompositon of BCRL. This study showed that cellulitis was associated with more excess volume, fat, and lean arm mass. Treatments should aim to prevent cellulitis in BCRL to possibly avoid the condition exacerbating.Cellulitis is a common complication in Breast Cancer-Related Lymphedema (BCRL). The excess amount of fat and lean mass in BCRL is a vital factor in patient stratification, prognosis, and treatments. However, it is not known whether cellulitis is associated with the excess fat and lean mass in BCRL. Therefore, this prospective observational study was designed to fundamentally understand the heterogonous biocomposition of BCRL. For this study, we consecutively enrolled 206 patients with unilateral BCRL between January 2019 and February 2020. All patients underwent Dual-Energy X-Ray Absorptiometry scans, bioimpedance spectroscopy, indocyanine green lymphangiography comprehensive history of potential risk factors, and a clinical exam. Multivariate linear and beta regression models were used to determine the strength of association and margins effect. Sixty-nine patients (33%) had at least one previous episode of cellulitis. Notably, a previous episode of cellulitis was associated with 20 percentage points more excess fat and 10 percentage points more excess lean mass compared to patients without cellulitis (p < 0.05). Moreover, each 1 increase in the patients BMI was associated with a 0.03 unit increase in the fat mass proportion of the lymphedema arm. Cellulitis was associated with more excess fat and lean arm mass in BCRL. In addition, patients BMI affect the proportion of fat mass in the arm.

Development and Psychometric Validation of a Patient-Reported Outcome Measure for Arm Lymphedema: The LYMPH-Q Upper Extremity Module

BackgroundA multiphased mixed-methods study was performed to develop and validate a comprehensive patient-reported outcome measure (PROM) for arm lymphedema in women with breast cancer (i.e., the LYMPH-Q Upper Extremity Module).MethodsQualitative interviews (January 2017 and June 2018) were performed with 15 women to elicit concepts specific to arm lymphedema after breast cancer treatment. Data were audio-recorded, transcribed, and coded. Scales were refined through cognitive interviews (October and Decemeber 2018) with 16 patients and input from 12 clinical experts. The scales were field-tested (October 2019 and January 2020) with an international sample of 3222 women in the United States and Denmark. Rasch measurement theory (RMT) analysis was used to examine reliability and validity.ResultsThe qualitative phase resulted in six independently functioning scales that measure arm symptoms, function, appearance, psychological function, and satisfaction with information and with arm sleeves. In the RMT analysis, all items in each scale had ordered thresholds and nonsignificant chi-square p values. For all the scales, the reliability statistics with and without extremes for the Person Separation Index were 0.80 or higher, Cronbach’s alpha was 0.89 or higher, and the Intraclass Correlation Coefficients were 0.92 or higher. Lower (worse) scores on the LYMPH-Q Upper Extremity scales were associated with reporting of more severe arm swelling, an arm problem caused by cancer and/or its treatment, and wearing of an arm sleeve in the past 12 months.ConclusionsThe LYMPH-Q Upper Extremity Module can be used to measure outcomes that matter to women with upper extremity lymphedema. This new PROM was designed using a modern psychometric approach and, as such, can be used in research and in clinical care.

Self-reported symptoms of arm lymphedema and health-related quality of life among female breast cancer survivors

We examined cross-sectional associations between arm lymphedema symptoms and health-related quality of life (HRQoL) in the Health, Eating, Activity and Lifestyle (HEAL) Study. 499 women diagnosed with localized or regional breast cancer at ages 35–64 years completed a survey, on average 40 months after diagnosis, querying presence of lymphedema, nine lymphedema-related symptoms, e.g., tension, burning pain, mobility loss, and warmth/redness, and HRQoL. Analysis of covariance models were used to assess HRQoL scores in relation to presence of lymphedema and lymphedema-related symptoms. Lymphedema was self-reported by 137 women, of whom 98 were experiencing lymphedema at the time of the assessment. The most common symptoms were heaviness (52%), numbness (47%), and tightness (45%). Perceived physical health was worse for women reporting past or current lymphedema than those reporting no lymphedema (P-value < 0.0001). No difference was observed for perceived mental health (P-value = 0.31). Perceived physical health, stress, and lymphedema-specific HRQoL scores worsened as number of symptoms increased (P-values ≤ 0.01). Women reporting tension in the arm had lower physical health (P-value = 0.01), and those experiencing burning pain, tension, heaviness, or warmth/redness in the arm had lower lymphedema-specific HRQoL (P-values < 0.05). Treatment targeting specific lymphedema-related symptoms in addition to size/volume reduction may improve some aspects of HRQoL among affected women.