Incidence Of Breast Cancer-related Lymphedema Research Articles

Lymphovenous Bypass for Immediate Lymphatic Reconstruction in Breast Cancer Patients Undergoing Axillary Lymph Node Dissection: Minimizing the Risk of Upper Extremity Lymphedema.

Studies have shown a significant reduction in breast cancer-related lymphedema (BCRL) rates in patients undergoing complete axillary lymph node dissection (cALND) combined with immediate lymphatic reconstruction (ILR) using lymphovenous bypass (LVB).The purpose of this study was to determine if ILR with LVB at the time of cALND results in a decreased incidence of BCRL and its impact on patient quality of life (QOL). In this prospective cohort study, patients ≥ 18 years requiring cALND underwent ILR from 2019 to 2021. The primary outcome was bilateral upper limb volumes measured by Brørson's truncated cone formula and the Pero-System (3D Körper Scanner). The secondary outcome was QOL measured by the Lymphedema Quality of Life (LYMQOL) arm patient-reported outcome measurement. Forty-two patients consented to ILR using LVB. ILR was completed in 41 patients with a mean of 1.9 ± 0.9 lymphovenous anastomosis performed. Mean age of patients was 52.4 ± 10.5 years with a mean body mass index of 27.5 ± 4.9 kg/m2. All patients (n = 39, 100%) received adjuvant therapy after ILR. Mean follow-up was 15.2 ± 5.1 months. Five patients met criteria for lymphedema throughout the duration of the study (12.8%), with two patients having resolution, with an overall incidence of 7.7% by the end of the study period. Patients with lymphedema were found to have statistically significant lower total LYMQOL values at 18 months (8.44 ± 1.17 vs. 3.23 ± 0.56, p < 0.001). A mean increase of 0.73 ± 3.5 points was observed for overall QOL average for upper limb function at 18 months compared with 3 months (t = 0.823, p = 0.425). This study showed an incidence of 7.7% lymphedema development throughout the duration of study. We also showed that ILR has the potential to reduce the significant long-term adverse outcomes of lymphedema and improve QOL for patients undergoing cALND.

Incidence and risk factors of breast cancer-related lymphedema in Korea: A nationwide retrospective cohort study.

Breast cancer-related lymphedema (BCRL) is a secondary lymphedema that occurs after breast cancer related treatments. BCRL develops from damage or dysfunction of the normally functioning lymphatic system due to surgery, radiation therapy and rarely due to cancer recurrence. This nationwide, retrospective study was aimed at investigating the incidence and risk factors of BCRL using the database of the Korean National Health Insurance Service (NHIS). Patients with newly diagnosed breast cancer who underwent breast surgery from January 1, 2017 to December 31, 2020, were recruited. The incidence was compared by four groups according to the operation type of breast cancer (breast conserving surgery (BCS) with sentinel lymph node biopsy (S), BCS with axillary lymph node dissection (A), total mastectomy (TM) with S, modified radical mastectomy(MRM)). The incidence rates of lymphedema were calculated by the number of incident events by the total follow-up period. Cox proportional hazard regression was used to calculate the risk of incidence of lymphedema based on a patients' characteristics, breast cancer treatment and comorbidities. The final cohort of operation subjects that satisfied the inclusion criteria was 34,676. BCRL occurred in 4,242 patients (12.2%), and the median follow-up period was 695.4 days. The BCRL was diagnosed in the BCS with S (8.0%), BCS with A (23.5%), TM with S (10.7%), MRM (28.5%) with an incidence of 40.8, 132.2, 55.8 and 171.8 per 1,000 person-years, respectively. Young age, obesity, chemotherapy, radiotherapy, residence in metropolitan areas and hyperlipidemia were identified as risk factors. In Korea, the incidence of BCRL was found to be 12.2%, with the highest risk observed among patients who underwent MRM. Therefore, surgical oncologists should meticulously assess the appropriate surgical approach and consider providing education to patients with risk factors for BCRL, aiming to ensure effective prevention strategies.

Is it the Type of Axillary Surgery or the Number of Removed Lymph Nodes That Increases the Risk of Breast Cancer Related Lymphedema (BCRL)? Results from a Prospective Screening Trial

Axillary surgery has been identified as the main risk factor for BCRL regardless the delivery of regional nodal radiation (RLNR). Yet it remains unknown if it is the type of axillary surgery or the number of removed lymph nodes (LN) that increases BCRL risks. Between 2008 and 2021, 3,350 patients (pts) who received surgery for breast cancer were enrolled in a lymphedema screening trial. Patients with bilateral breast cancer or without axillary surgery were excluded. Perometry was used to assess limb volume preoperatively in all patients. BCRL was defined as a ≥10% relative arm-volume increase arising >3 months postoperatively. The cohort was divided by axillary surgery type: axillary lymph node dissection (ALND) and sentinel lymph node biopsy (SLNB). Radiation was delivered using 3D conformal technique and RLNR was defined as the usage of anterior supraclavicular field. No hypofractionation was used and doses ranged between 50 and 50.4 Gy in 25-28 fractions. Multivariable Cox proportional hazard models compared the cumulative incidence of BCRL and local failure between different patient groups. After applying inclusion criteria, 2,623 pts were available with overall median follow-up s of 6.1 years. Of the entire cohort, 709 (27%) had ALND with a median of 16 LN removed, while 1,914 (73%) received SLNB only with a median of 2 LN removed. The median number of malignant LN and patients receiving RLNR was higher in ALND group compared to SLNB only group. Frequency distribution analysis showed that the main overlap between ALND and SLNB only groups happen in the range of 3-11 LN removed. Therefore, the primary analysis focused only on pts with 3-11 LN across both groups (n = 690: ALND n = 140, SLNB n = 550). The multivariable model adjusted for BMI, RLNR, age and breast surgery showed that in this group with 3-11 LN removed in both cohorts, ALND remained significantly associated with BCRL (HR: 4.2, p<0.0001). Separate analyses for the entire SLNB only group and ALND groups were conducted to evaluate if the BCRL risk increases per each removed LN within the same axillary surgery group. The multivariable analysis for SLNB only pts(N = 1,914) showed that for each LN removed the risk of BCRL did not increase significantly (HR:1.06, p = 0.3), similarly for ALND group (N = 709) for each LN removed (HR:1.02, p = 0.08). For pts with pathologic N2-N3 disease and clinical node negative without neoadjuvant chemotherapy receiving ALND, the number of LN removed did not significantly improve neither Local control (HR:1.02, p = 0.8) nor distant disease survival (HR:1.01, p = 0.6). ALND procedure per se is the main risk factor for BCRL not the number of LNs removed. For high-risk pts with >N2 disease, aggressive ALND did not improve tumor outcome. De-escalation with targeted axillary sampling followed by RLNR should be evaluated. Future lymphedema research should account for type of axillary surgery instead of number of LNs removed as a factor. (NCT01521741).

The efficacy in shoulder range of motion of a snapping manual maneuver added to a standardized exercise protocol in axillary web syndrome: a randomized controlled trial

Purpose Axillary Web Syndrome (AWS) is a common sequela after surgical axillary lymph node dissection (ALND) often manifesting with reduced range of motion (ROM) of the limb, which requires rehabilitation. Notwithstanding, a standardized rehabilitation protocol is currently lacking in clinical practice. Our primary objective was therefore to evaluate the effectiveness of the use of a snapping manual maneuver (SMM, used in our clinical practice) to increase ROM during abduction (ABD) when compared with a standardized stretching exercise (SSE) protocol. A three-year follow-up of the enrolled patients was also carried out to determine the incidence of Breast Cancer-Related Lymphedema (BCRL). Materials and methods Between July 2013 and January 2019, we conducted a single-blinded randomized clinical trial. A total of 60 patients, who underwent ALND in our hospital, came to our clinic under medical advice or on voluntary access and reported AWS symptoms. The patients were randomly assigned into two equally divided groups. The treatment of group one consists in the execution of a supervised SSEs protocol, while group two additionally received a manual snapping maneuver. Patients of both groups received two treatment sessions within two weeks. At the end of the session, they were asked to continue the exercises autonomously on a daily basis, three times per day, for one month. Results There were no statically significant differences in ROM at our one-month follow-up and the incidence of BCRL was equally distributed after three years. Conclusions The use of the manual snapping maneuver in addition to stretching once per week for two weeks does not appear to improve the outcome of the patients in comparison with stretching alone and does not appear to be related to lymphedema in our 3 years follow-up.

A Prospective Study of Radiation Therapy After Immediate Lymphatic Reconstruction: Analysis of the Dosimetric Implications

Axillary lymph node dissection (ALND) and regional nodal irradiation (RNI) are the primary causes of breast cancer-related lymphedema (BCRL). Immediate lymphatic reconstruction (ILR) is a novel surgical procedure that reduces the incidence of BCRL after ALND. The ILR anastomosis is placed in a location thought to be outside the standard radiation therapy fields to prevent radiation-induced fibrosis of the reconstructed vessels; however, there is excess risk of BCRL from RNI even after ILR. The purpose of this study was to understand the radiation dose distribution in relation to the ILR anastomosis. This prospective study included 13 patients treated with ALND/ILR from October 2020 to June 2022. A twirl clip deployed during surgery was used to identify the ILR anastomosis site during radiation treatment planning. All cases were planned using a 3D-conformal technique with opposed tangents and an obliqued supraclavicular (SCV) field. RNI deliberately targeted axillary Levels 1 to 3 and the SCV nodal region in 4 patients and was limited to Level 3 and SCV nodes in 9 patients. The ILR clip was located in Level 1 in 12 patients and Level 2 in 1 patient. In patients with radiation directed at only Level 3 and SCV, the ILR clip was still within the radiation field in 5 of these patients and received a median dose of 3939 cGy (range, 2025-4961 cGy). The median dose to the ILR clip was 3939 cGy (range, 139-4961 cGy) for the entire cohort. The median dose was 4275 cGy (range, 2025-4961 cGy) when the ILR clip was within any radiation field and 233 cGy (range, 139-280 cGy) when the clip was outside all fields. The ILR anastomosis was often directly irradiated with 3D-conformal techniques and received substantial radiation dose, even when the site was not deliberately targeted. Long-term analysis will help determine whether minimizing radiation dose to the anastomosis will decrease BCRL rates.

A 4-Year Institutional Experience of Immediate Lymphatic Reconstruction.

Up to one in three patients may go on to develop breast cancer-related lymphedema (BCRL) after treatment. Immediate lymphatic reconstruction (ILR) has been shown in early studies to reduce the risk of BCRL, but long-term outcomes are limited because of its recent introduction and institutions' differing eligibility requirements. This study evaluated the incidence of BCRL in a cohort that underwent ILR over the long term. A retrospective review of all patients referred for ILR at the authors' institution from September of 2016 through September of 2020 was performed. Patients with preoperative measurements, a minimum of 6 months of follow-up data, and at least one completed lymphovenous bypass were identified. Medical records were reviewed for demographics, cancer treatment data, intraoperative management, and lymphedema incidence. A total of 186 patients with unilateral node-positive breast cancer underwent axillary nodal surgery and an attempt at ILR over the study period. Ninety patients underwent successful ILR and met all eligibility criteria, with a mean patient age of 54 ± 12.1 years and median body mass index of 26.6 kg/m 2 [interquartile range (IQR), 24.0 to 30.7 kg/m 2 ]. The median number of lymph nodes removed was 14 (IQR, eight to 19). Median follow-up was 17 months (range, 6 to 49 months). Eighty-seven percent of patients underwent adjuvant radiotherapy, and among them, 97% received regional lymph node irradiation. The overall rate of lymphedema was 9% at the end of the study period. With the use of strict follow-up guidelines over the long term, the authors' findings support that ILR at the time of axillary lymph node dissection is an effective procedure that reduces the risk of BCRL in a high-risk patient population. Therapeutic, IV.

Abstract P2-14-10: Axillary Reverse Mapping Aids in Reducing the Rates of BCRL in Underserved Ethnically Diverse Population

Abstract Background: Breast Cancer Related Lymphedema (BCRL), is a long-term side effect affecting the patient’s quality of life after lymph node surgery. Historically BCRL is seen in 5-7% and 15-40% of patients undergoing sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) respectively; with the risk increasing two-fold in low-income and ethnic minority groups. Axillary Reverse Mapping (ARM) is a novel technique to distinguish drainage pathways of the arm and breast, and prior studies have reported significantly lower rates of BCRL with ARM. Lymphatic re-approximation can prevent and/or reduce lymphedema rates in cases where crossover nodes are encountered. Furthermore, blue nodes can be preserved during ALND; however, if resected during ALND, lymphatic venous (LYMPHA) procedure can help to restore lymphatic flow. However, there is a paucity of literature looking at the utility of ARM in ethnically minority groups. Therefore, we aimed to evaluate the prevalence of lymphedema in our patient population with breast cancer undergoing SLNB and ALND using ARM and in turn compare these findings to historical controls. Materials &amp; Methods: A retrospective study was carried out on patients who underwent axillary surgery with ARM from January 2019 to July 2021. Patient demographics such as age, BMI, gender, and ethnicity were recorded. Patients undergoing mastectomy vs breast conservation with SLNB ± ALND associated with ARM were monitored for lymphedema for a year at 3-month intervals using SOZO® scores, and then for another 2 years clinically. At each follow-up, SOZO® scores were computed using bioimpedance spectroscopy and compared to preoperative baseline scores. Results: A total of 142 patients’ data was evaluated, of which 83.8% belonged to the minority group (African American = 46, Hispanic = 63, Asian = 10). Mean BMI accounted for 29.1+5.31. Breast conservation surgery and mastectomy were performed in 71.8% (n=102) and 28.1% (n=40) of patients respectively. SLNB was performed on 88.7% (n=126) of the patients and ALND was carried out on 11.3% (n=16). Furthermore, 73.9% (n=105) of the patients underwent radiation therapy. Positive lymph nodes were identified in 24.6% (n=35) of patients. Blue nodes and blue lymphatics were encountered in 17.6% (n=25) and 32.4% (n=46) of patients respectively. Out of the blue nodes identified (n=25), 44% (n=11) were excised and 32% (n=8) were diagnosed as crossover nodes. All the crossover nodes were resected but none of them contributed to the development of lymphedema. Moreover, 90.9% of the patients with blue lymphatics underwent lymphatic re-approximation after excision of the blue nodes. Of the 142 patients, 59 had a three-month follow-up of which 2 patients (3.4%) developed clinical lymphedema diagnosed via SOZO® who had undergone SLNB which resolved by 6-month follow-up. Additionally, compared to the historical incidence of BCRL which accounts for up to 40.4% in ethnic minorities, we found a significantly lower incidence of lymphedema (p&amp;lt; 0.001) in our patient population. Moreover, in our study, ALND and radiation therapy did not contribute to lymphedema rates. Conclusion: ARM procedure can significantly lower BCRL even in ethnically minority groups. 3.4% of patients undergoing SLNB developed BCRL, which was significantly lower than historically reported data. Furthermore, in our study, no patients who underwent ALND developed lymphedema. Also, crossover nodes or radiation therapy did not contribute to the development of lymphedema after surgery demonstrating the effectiveness of ARM technique. Further studies with larger sample size and longer follow-up duration are necessary to better understand the utility of ARM technique in this population. Table 1 Baseline characteristics and follow-up data of the patients undergoing Axillary Reverse Mapping with SLNB ± ALND Citation Format: Fardeen Bhimani, Maureen McEvoy, Kelly Johnson, Sheldon Feldman. Axillary Reverse Mapping Aids in Reducing the Rates of BCRL in Underserved Ethnically Diverse Population [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 P2-14-10.

Stellate Ganglion Block Improves Postoperative Sleep Quality and Analgesia in Patients with Breast Cancer: A Randomized Controlled Trial.

Postoperative impaired sleep quality and pain are associated with adverse outcomes. Stellate ganglion block (SGB) has shown promising results in enhancing sleep quality and alleviating neuropathic pain. This study aimed to investigate the effects of ultrasound-guided SGB on postoperative sleep quality and pain in patients undergoing breast cancer surgery. This study is a parallel-group randomized controlled clinical trial with two groups: SGB and control. Fifty female patients undergoing breast cancer surgery were randomized in a 1:1 ratio to receive preoperative ultrasound-guided single-injection SGB (SGB group) or just an ultrasound scan (control group). All participants were blinded to the group assignment. The primary outcome was postoperative sleep quality, assessed by the St. Mary's Hospital Sleep Questionnaire and actigraphy 2days postoperatively. The secondary outcome was postoperative pain, measured by thevisual analog scale. A total of 48 patients completed the study, with 23 patients in the control group and 25 in the SGB group. The postoperative St. Mary's Hospital Sleep Questionnaire scores were significantly higher in the SGB group than in the control group on 1day postoperative (30.88 ± 2.44 versus 27.35 ± 4.12 points, P = 0.001). The SGB also increased the total sleep time and sleep efficiency (main actigraphy indicators) during the first two postoperative nights. Compared with the control group, preoperative SGB reduced postoperative pain and the incidence of breast cancer-related lymphedema (20% versus 52.2%, P = 0.02, odds ratio 0.229, 95% confidence interval 0.064-0.821). There were no adverse events related to SGB. Preoperative ultrasound-guided SGB improves postoperative sleep quality and analgesia in patients undergoing breast cancer surgery. SGB may be a safe and practical treatment to enhance the postoperative quality of life in patients with breast cancer. The study was registered in the Chinese Clinical Trial Registry (ChiCTR2100046620, principal investigator: Kai Zeng, date of registration: 23 May 2021).

Breast cancer-related lymphedema correlated with incidence of cellulitis and mortality.

This study investigated breast cancer-related lymphedema (BCRL) and its correlation with the incidence of cellulitis and mortality in the National Health Insurance (NHI) database in Taiwan. Between 2004 and 2014, the NHI database of patients with breast cancer who underwent surgical procedures, adjuvant therapies, BCRL, cellulitis, and mortality were retrospectively reviewed. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for incidence of BCRL and cellulitis in different treatment groups. The associations of BCRL with the incidence of cellulitis and mortality were further analyzed using the Kaplan-Meier curve. Among 100 301 patients, 5464 (5.4%) developed BCRL with a median onset of 1.3 years. At a mean follow-up of 4.77 years, the incidence of cellulitis in the BCRL group (12.7%, 694/5464 patients) was significantly higher than in the no-BCRL group (2.73%, 2589/94 837 patients) (HR: 3.74; 95% CI: 3.43-4.08; p < 0.0001). At a mean follow-up of 5.77 years, the mortality rate in the cellulitis group (34.21%, 1123/3283 patients) was significantly greater than in the no-cellulitis group (16.29%, 15 804/97 018 patients) (HR: 1.17; 95% CI: 1.1-1.24; p < 0.0001). BCRL had a significantly higher incidence of cellulitis and mortality.

Lymphedema in Inflammatory Breast Cancer Patients Following Trimodal Treatment.

Breast cancer-related lymphedema (BCRL) is a debilitating sequela of breast cancer treatment and is becoming a greater concern in light of improved long-term survival. Inflammatory breast cancer (IBC) is a rare and aggressive malignancy for which systemic therapy, surgery, and radiotherapy remain the standard of care, thereby making IBC patients highly susceptible to developing BCRL. This study evaluated BCRL in IBC following trimodal therapy. IBC patients treated from 2016 to 2019 were identified from an institutional database. Patients were excluded if they presented with recurrent disease, underwent bilateral axillary surgery, did not complete trimodal therapy, or were lost to follow-up. Demographic, clinicopathologic factors, oncologic outcomes, and perometer measurements were recorded. BCRL was defined by clinician diagnosis and/or objective perometer measurements when available. Time to development of BCRL and treatment received were captured. Eighty-three patients were included. Median follow-up was 33 months. The incidence of BCRL was 50.6% (n = 42). Mean time to BCRL from surgery was 13 (range 2-24) months. Demographic and clinicopathologic features were similar between patients with and without BCRL with exception of higher proportion receiving delayed reconstruction in the BCRL group (38.1% vs. 14.6%, p = 0.03). Forty patients (95.2%) underwent BCRL treatment, which included physical therapy (n = 39), compression (n = 38), therapeutic lymphovenous bypass (n = 13), and/or vascularized lymph node transfer (n = 12). IBC patients are at high-risk for BCRL after treatment, impacting 51% of patients in this cohort. Strategies to reduce or prevent BCRL and improve real-time diagnosis should be implemented to better direct early management in this patient population.

BREAST CANCER-RELATED LYMPHEDEMA: RISK FACTORS, DIAGNOSIS, MANAGEMENT, PREVENTION

Breast cancer-related lymphedema (BCRL) is a negative outcome of breast cancer or its treatment, which affects 1 of every 5 patients. Disruption of the lymph flow results in its accumulation in the tissues with resulting edema. Diagnosis is based on the presence of symptoms such as progressive upper extremity swelling, limb pain and discomfort, skin changes, restricted range of motion, and the measurement of the extremity girth. First-line treatment is nonivasive, which includes compressions or physiotherapy. Prevention strategy focuses on compres­sion therapy or exercises, however, limiting the extent of lymph node removal is the only measure shown to reduce the incidence of BCRL.

Relationship of Adjuvant Radiation and the Lymphedema Index: A Valuable Trend to Follow Subclinical Lymphedema in Patients After Immediate Lymphatic Reconstruction.

Immediate lymphaticovenular bypass (immediate lymphatic reconstruction [ILR]) at the time of axillary lymph node dissection has emerged as a preventative paradigm to decrease the incidence of breast cancer-related lymphedema in high-risk patients. These patients are often treated with adjuvant therapies, including radiation. Bioimpedance spectroscopy is a validated tool for trending breast cancer-related lymphedema and identifying subclinical disease. Lymphedema Index (LDEX) values are commonly obtained in ILR patients; however, postoperative trends and relationships with adjuvant treatments are yet to be reported in the literature. After International Review Board approval, 100 consecutive patients underwent axillary lymph node dissection with axillary reverse lymphatic mapping and ILR at a tertiary cancer center. These patients were then followed prospectively in a multidisciplinary lymphedema clinic at 3-month intervals with clinical examination, circumferential limb girth measurements and bioimpedance spectroscopy (LDEX). Seventy-two patients met inclusion for analysis at 3 months, 60 at 6 months, 51 at 9 months, 45 at 12 months, 41 at 15 months, and 22 at 18 months. A majority of the patients included underwent adjuvant radiation. Average LDEX score for patients who developed lymphedema was 3.02 at 3 months, at 29.1 months, 17.8 at 9 months, 15.05 at 12 months, 18.75 at 15 months, and 7.7 at 18 months. Patients who went on to develop lymphedema had a higher LDEX score at 6 months (29.1 vs 3.20, P = 0.1329), which reached a significant difference beginning at 9 months (17.8 vs 3.19, P = 0.0004). All patients who went on to develop lymphedema received adjuvant radiation. These data provide valuable insight guiding follow-up after ILR. Six-month LDEX is much higher in patients who developed lymphedema, all of which underwent adjuvant radiation therapy, which correlates with the time of completion of their treatment. Average LDEX value after this remains significantly higher in this population. Patients who demonstrate this increase in LDEX and received adjuvant radiation are at highest risk to develop lymphedema despite ILR. All patients who developed lymphedema despite ILR had adjuvant radiation, and this is likely a contributing factor. Injury from adjuvant radiation and its impact after ILR is not insignificant and warrants further studies.

Immediate Lymphatic Reconstruction during Axillary Node Dissection for Breast Cancer: A Systematic Review and Meta-analysis.

Background:The objective of this study is to summarize the current body of evidence detailing the impact of immediate lymphatic reconstruction (ILR) on the incidence of breast cancer-related lymphedema (BCRL) following axillary node dissection (ALND).Methods:Medline and Embase databases were queried for publications, where ILR was performed at the time of ALND for breast cancer. Exclusion criteria included lymphaticovenous anastomosis for established BCRL, animal studies, non-breast cancer patient population studies, and descriptive studies detailing surgical technique. Meta-analysis was performed with a forest plot generated using a Mantel -Haenszel statistical method, with a random-effect analysis model. Effect measure was reported as risk ratios with associated 95% confidence intervals. The risk of bias within studies was assessed by the Cochrane Collaboration tool.Results:This systematic review yielded data from 11 studies and 417 breast cancer patients who underwent ILR surgery at the time of ALND. There were 24 of 417 (5.7%) patients who developed BCRL following ILR. Meta-analysis revealed that in the ILR group, 6 of 90 patients (6.7%) developed lymphedema, whereas in the control group, 17 of 50 patients (34%) developed lymphedema. Patients in the ILR group had a risk ratio of 0.22 (CI, 0.09 -0.52) of lymphedema with a number needed to treat of four.Conclusions:There is a clear signal indicating the benefit of ILR in preventing BCRL. Randomized control trials are underway to validate these findings. ILR may prove to be a beneficial intervention for improving the quality of life of breast cancer survivors.

59. A FOUR-YEAR INSTITUTIONAL EXPERIENCE OF IMMEDIATE LYMPHATIC RECONSTRUCTION

PURPOSE: Up to one in three breast cancer patients undergoing axillary lymph node dissection (ALND) and radiation develop breast cancer related lymphedema (BCRL). Immediate lymphatic reconstruction (ILR) is a surgical procedure that has been shown in early studies to reduce the risk of BCRL. However, longer-term outcomes are limited. This study evaluates the incidence of BCRL in a cohort that underwent ILR over the long-term. METHODS: A retrospective review of patients brought to the OR for ILR at our institution from September 1st, 2016 until September 1st, 2020 was performed. Patients with preoperative measurements not consistent with lymphedema, at least one bypass performed, and minimum 6-months follow-up were identified. Records were reviewed for demographics, cancer treatment data, intra-operative management, and lymphedema incidence. Eligible patients were followed through February 2021. RESULTS: A total of 186 women with unilateral node-positive breast cancer underwent ALND and attempted ILR. 90 patients underwent successful ILR and met inclusion/exclusion criteria. Mean age was 53.9 (SD 12.5) years and median BMI 26.6 (Q1-Q3 24.0-29.9) kg/m2. Median number of lymph nodes removed was 14 (8-19). 87% of patients underwent adjuvant radiotherapy of which 97% received regional lymph node radiation. Median follow-up was 17 months (range: 6-49). 15.5% had a minimum of 1 surveillance visit consistent with lymphedema. At the study conclusion, 6.7% had resolved. The final rate of BCRL was 8.8%. CONCLUSION: Utilizing strict follow-up guidelines over the long-term, our findings support ILR at time of axillary surgery as a safe procedure that reduces the risk of BCRL.

Reverse Lymphatic Mapping and Immediate Microsurgical Lymphatic Reconstruction Reduces Early Risk of Breast Cancer-Related Lymphedema.

Breast cancer-related lymphedema is a progressive disease that poses tremendous physical, psychosocial, and financial burden on patients. Immediate lymphaticovenular anastomosis at the time of axillary lymph node dissection is emerging as a potential therapeutic paradigm to decrease the incidence of breast cancer-related lymphedema in high-risk patients. Eighty-one consecutive patients underwent reverse lymphatic mapping and, when feasible, supermicrosurgical immediate lymphaticovenular anastomosis at the time of axillary lymph node dissection at a tertiary care cancer center. Patients were followed prospectively in a multidisciplinary lymphedema clinic (plastic surgery, certified lymphatic therapy, dietary, case management) at 3-month intervals with clinical examination, circumferential limb girth measurements, and bioimpedance spectroscopy. An institutional control cohort was assessed for the presence of objectively diagnosed and treated breast cancer-related lymphedema. Data were analyzed by a university statistician. Seventy-eight patients met inclusion, and 66 underwent immediate lymphaticovenular anastomosis. Mean follow-up was 250 days. When compared to a retrospective control group, the rate of lymphedema in patients who underwent immediate lymphaticovenular anastomosis was significantly lower (6 percent versus 44 percent; p < 0.0001). Patients with 6-month follow-up treated with combined adjuvant radiation therapy and chemotherapy had significantly greater risk of developing breast cancer-related lymphedema (p = 0.04) compared to those without combined adjuvant therapy. Arborized anastomotic technique had a statistically shorter operative time than end-to-end anastomosis (p = 0.005). This series of consecutive patients demonstrate a 6 percent incidence of early-onset breast cancer-related lymphedema with immediate lymphaticovenular anastomosis and an increased risk in those undergoing combined adjuvant treatment. These early data represent an encouraging and substantial decrease of breast cancer-related lymphedema in high-risk patients. Therapeutic, III.

Abstract GS4-01: Impact of race and ethnicity on incidence and severity of breast cancer related lymphedema after axillary lymph node dissection: Results of a prospective screening study

Abstract GS4-01: Impact of race and ethnicity on incidence and severity of breast cancer related lymphedema after axillary lymph node dissection: Results of a prospective screening study

Abstract P3-19-08: Breast cancer related lymphedema in patients undergoing RNI: Is the axillary lateral vessel thoracic junction an organ-at-risk?

Abstract Background: Breast-cancer related lymphedema (BCRL) is a devastating treatment complication driven by the extent of axillary surgery (axillary lymph node dissection [ALND] versus sentinel lymph node biopsy [SLNB]). Regional nodal irradiation (RNI) may increase the risk of BCRL by up to 5%. Recently, investigators identified a region of the axilla known as the axillary-lateral thoracic vessel juncture (ALTJ) as a potential organ-at-risk (OAR) demonstrating that increasing radiation dose to the ALTJ was associated with a higher risk of BCRL. Here, we set to validate whether radiation dose to the ALTJ is associated with BCRL. Materials/Methods: We identified patients with stage II-III breast cancer treated with adjuvant RNI after M or L from 2013-2018 excluding those with BCRL pre-radiation. RNI treatment planning included delineation of clinical target volumes (CTVs): breast or chest wall and regional lymph nodes per the RTOG Breast Cancer Atlas. The CTVs were expanded by 5mm to create the planning target volume (PTV). Dose delivered was 50 Gy/25 fractions with goal of 47.5 Gy (95%) to 95% of each PTV. We defined BCRL as difference in arm circumference between the ipsilateral and contralateral limb &amp;gt;2.5 cm at any 1 visit or ≥2 cm on at least 2 visits. All patients suspected of having BCRL at routine follow-up visits were evaluated by physical therapy. The ALTJ was retrospectively contoured and the following metrics collected: maximum/minimum/mean dose; V10Gy-V50Gy. Follow-up time was defined as the time from surgery to the development of BCRL or last follow-up. Cox proportional hazards regression models were used to test the association between clinical and dosimetric parameters with the development of BCRL. All variables with p&amp;lt;0.10 on univariate analysis were entered in the final multivariate model (p&amp;lt;0.05 considered statistically significant). Results: Population includes 378 patients with median age 53 years (interquartile range [IQR], 45-61 years), median body mass index (BMI) 28.4 kg/m2 (IQR, 24.3-33.4 kg/m2), 60% HR+/HER2-, 89% chemotherapy, 53% stage III, 71% underwent M, and 82% underwent ALND with median of 18 nodes removed (IQR, 11-25) and median of 2+ nodes (IQR, 1-5). Median follow-up time was 54.5 months (IQR, 40.3-72.2 months). The ALTJ and axilla PTV overlapped in 91% of the patients. BCRL developed in 97 patients (25.7%) at a median of 18.9 months (IQR, 9.9-30.6 months). The 4-year cumulative incidence of BCRL was 23.5% (26.6% ALND vs. 8.7% SLNB, p=0.002). On univariate analysis, increasing age (HR=1.02, p=.039), increasing BMI (HR=1.04, p=0.002), increasing number of nodes removed (HR=1.04, p&amp;lt;0.0001), and use of IMRT vs. 3DCRT (HR=1.50, p=0.041) were all significantly associated with developing BCRL while increasing size of the axilla PTV (HR=0.96, p=0.047) was associated with a lower risk. None of the ALTJ metrics were associated with developing BCRL. Increasing ALTJ V45 was marginally associated with a lower risk of BCRL (HR=0.96, p=0.091). On multivariate analysis, increasing age (HR=1.02, p=0.021), increasing BMI (HR=1.04, p=0.004), and increasing number of nodes removed (HR=1.03, p=0.001) were associated with a higher risk of developing BCRL while use of IMRT (HR=1.24, p=0.338), size of the axilla PTV (HR=0.96, p=0.110) and ALTJ V45 (HR=0.99, p=0.708) were not. There were 10 local-regional recurrence (LRR) events as a first failure, 8 of which occurred with simultaneous distant metastases (DM). Of these LRRs, 5 included an axillary nodal component (all with DM) resulting in a 2.6% 4-year LRR rate (1.4% axillary recurrence rate). Conclusion: In this analysis, ALTJ is not validated as a critical OAR for reducing BCRL risk. Until such an OAR is discovered, the axillary PTV should not be modified or dose reduced in efforts to reduce BCRL given the low LRR and inability to validate ALTJ as an OAR. Citation Format: Erin Healy, Sachin Jhawar, Sasha Beyer, Julia R White, Jose G Bazan. Breast cancer related lymphedema in patients undergoing RNI: Is the axillary lateral vessel thoracic junction an organ-at-risk? [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-08.

Evaluation of the Effect of Axillary Radiotherapy Dose and the Development of Lymphedema in Breast Cancer Patients

Purpose: The present study is aiming to correlate different radiotherapy techniques, fractionations, and doses received by each axillary LN level and axillary vessels with the development of breast cancer-related lymphedema (BCRL). Methods and Materials: We retrospectively studied 181 female breast cancer patients who were diagnosed and treated by radiation therapy during the period from January 2012 to December 2017. The radiotherapy treatment plans were recalled from the archives. The axillary LN levels I, II, III, supraclavicular LN were contoured as well as axillary vessels. New dose volume histograms were generated to correlate between the radiotherapy dose t and the development of BCRL. Results: The study included 162 patients treated with a 3D radiotherapy technique and 19 treated with a 2D radiotherapy technique; 124 patients underwent MRM, while 57 patients underwent BCS; 117 patients were treated with a hypofractionated technique, while 64 patients were treated with a conventional radiotherapy technique. The cumulative incidence of BCRL after radiotherapy was 20.4%. There was a statistically significant relationship between the 2D radiotherapy technique compared with 3DCRT and development of lymphedema (55 vs. 16.6, respectively; p < 0.001). Patients who were treated with conventional radiotherapy had significantly higher rates of lymphedema (42.2%) compared with hypofractionated radiotherapy (8.5%) (p < 0.001). There was a non-significant relationship between mean radiotherapy dose to axillary levels or axillary vessels and development of lymphedema. Conclusion: Breast cancer radiotherapy with the 2D technique and conventional fractionation protocol might increase the risk of BCRL. No correlation was observed between radiotherapy dose to each axillary LN level, axillary vessels and BCRL.

Development and Validation of an Intraoperative Nomogram to Predict Breast Cancer-Related Lymphedema Based on the Arm Lymphatics Distribution.

Preoperatively determining those patients who are at high risk of encountering breast cancer-related lymphedema (BCRL) is still not well understood. This study aimed to develop a simple intraoperative nomogram for BCRL, incorporating a protective factor. Overall, 320 breast cancer patients at Zhongnan Hospital (training set) and 221 patients at Dongfeng General Hospital (external validation cohort) treated between November 2017 and December 2018 were included. Prior to axillary lymph node dissection (ALND), 1mL (2.5 mg) of indocyanine green was administered to the area of the internal bicipital sulcus of the upper limb. The fluorescence image was obtained and the proportion of arm lymph flow above the level of the axillary vein was calculated. Multivariate logistic regression was performed using this proportion together with clinical data. A nomogram was then constructed and assessed for its discrimination and calibration ability and clinical utility in the training and external validation sets. The cumulative incidence of BCRL was 18.7% (60/320), with a median follow-up of 29months (20-34). In the multivariate logistic regression analysis, body mass index, taxane, radiotherapy, and proportion of arm lymph flow above the level of the axillary vein were identified as independent risk factors. In the training and validation cohorts, the calibration curve performed well (p=0.721 and p=0.315, respectively), and the area under the receiver operating characteristic curve values were 0.829 (95% confidence interval [CI] 0.773-0.885) and 0.804 (95% CI 0.732-0.877), respectively. High-risk patients could be identified intraoperatively with this nomogram, and timely intervention could be performed with preservation of the arm lymphatics.

The effectiveness of axillary reverse mapping in preventing breast cancer-related lymphedema: a meta-analysis based on randomized controlled trials.

Here, we carried out an extensive meta-analysis to investigate the effectiveness of the use of axillary reverse mapping (ARM) during axillary lymph node dissection (ALND) in preventing breast cancer-related lymphedema (BCRL). Database searches to identify relevant randomized controlled trials (RCTs) were performed of MEDLINE (PubMed), Web of Science, Embase, and the Cochrane Library. Eligible articles with a publication date from database establishment to December 2020 were retrieved by combining keywords including: "breast cancer", "breast carcinoma", "breast neoplasm", "axillary reverse mapping", "axillary lymph node dissection", "lymphatic arm drainage", and "lymphedema". Independent data extraction was conducted, and Review Manager (version 5.3) was used for statistical analyses. Five eligible RCTs were included in the meta-analysis. A total of 37 patients suffered arm lymphedema (37/786, 4.71%) in the experimental group (ARM during ALND), compared with 164 arm lymphedemas (164/873, 18.79%) in the control group (ALND alone). The results showed that ARM during ALND was superior to ALND alone in reducing the incidence of BCRL [OR =0.20, 95% confidence intervals (CI): 0.13-0.29, P<0.00001]; however, the 2 procedures did not differ significantly in terms of oncological safety or shoulder movement (OR =0.30, 95% CI: 0.03-2.96, P=0.30; OR =0.44, 95% CI: 0.14-1.40, P=0.17). ARM during ALND can prevent and reduce the occurrence of BCRL in patients with early-stage BC during long-term follow-up. Due to the limited number of RCTs available, more in-depth, high-quality RCTs are urgently needed to provide a reliable and convincing basis for the application of ARM during ALND.