Axillary Reverse Mapping Nodes Research Articles

Evolution of Indocyanine Green Fluorescence in Breast and Axilla Surgery: An Australasian Experience.

The evolution of indocyanine green (ICG) fluorescence in breast and axilla surgery from an Australasian perspective is discussed in this narrative review with a focus on breast cancer and reconstruction surgery. The authors have nearly a decade of experience with ICG in a high-volume institution, which has resulted in publications and ongoing future research evaluating its use for predicting mastectomy skin flap perfusion for reconstruction, lymphatic mapping for sentinel lymph node (SLN) biopsy, and axillary reverse mapping (ARM) for prevention of lymphoedema. In the authors' experience, routine use of ICG angiography during breast reconstruction postmastectomy was demonstrated to be cost-effective for the reduction of ischemic complications in the Australian setting. A novel tracer combination, ICG-technetium-99m offered a safe and effective substitute to the "gold standard" dual tracer for SLN biopsy, although greater costs were associated with ICG. An ongoing trial will evaluate ARM node identification using ICG fluorescence during axillary lymph node dissection and potential predictive factors of ARM node involvement. These data add to the growing literature on ICG and allow future research to build on this to improve understanding of the potential benefits of fluorescence-guided surgery in breast cancer and reconstruction surgery.

Axillary Reverse Mapping in Clinically Node-Positive Breast Cancer Patients

Background: Axillary reverse mapping (ARM) nodes are involved in a significant proportion of clinically node-positive (cN+) breast cancer patients. However, neoadjuvant chemotherapy (NAC) is effective at decreasing the incidence of nodal metastases in cN+ patients. Patients and methods: One hundred forty-five cN+ patients with confirmed nodal involvement on ultrasound-guided fine needle aspiration cytology were enrolled in this study: one group underwent axillary lymph node dissection (ALND) without NAC (upfront surgery group), and the other group underwent ALND following NAC (NAC group). The patients underwent 18F-FDG-positron emission tomography/computed tomography (18F-FDG-PET/CT) before surgery, as well as an ARM procedure during ALND. Results: the rates of involvement of ARM nodes in the NAC group were significantly lower than those of the upfront surgery group (36.6% vs. 62.2%, p < 0.01). Notably, involvement was significantly decreased after NAC in non-luminal-type tumors as compared to the luminal-type (18.4% vs. 48.5%: p < 0.01). Moreover, there was a significant difference in ARM node involvement after NAC between patients with or without axillary uptake of 18F-FDG (61.5% vs. 32.5%: p < 0.01). Conclusions: NAC significantly decreased the risk of ARM node metastases in cN+ patients, but 18F-FDG-PET/CT was not suitable to detect residual metastatic disease of the axilla after NAC.

Triple mapping for axillary staging after neoadjuvant therapy: Axillary reverse mapping with indocyanine green and dual agent sentinel lymph node biopsy

Axillary staging is 1 of the major issues of current breast cancer management after neoadjuvant systemic therapy (NST). Sentinel lymph node biopsy (SLNB) is an option for clinically node negative patients. Axillary reverse mapping (ARM) was introduced to identify and preserve the lymphatic drainage from the arm. The aim of the presented study is to employ triple mapping (radiocolloid, blue dye and indocyanine green [ICG]) to assess the crossover rate and metastatic involvement of ARM nodes after NST. Clinically node positive patients before NST who were converted to N0 and scheduled for targeted axillary dissection were included. sentinel lymph node (SLN) mapping was performed via dual agent mapping. ICG was used for ARM procedure. Blue, hot and fluorescent nodes and lymphatics were visualized in the axilla using infrared camera system and dual opto-nuclear probe (Euoroprobe3). Fifty-two patients underwent targeted axillary dissection and ARM procedures 12 out of whom had axillary node dissection. 45 of the 52 patients had at least 1 hot or blue SLN identified intraoperatively. Of these, 61.5% cases had hot SLNs, 42.3% had hot and blue, 15.4% had hot/blue/fluorescent, 7.7% had blue/fluorescent, 6 11.5% had hot/fluorescent and 7 13.5% had only clipped nodes. The overall identification rate of ARM-nodes by means of ICG technique was 86.5%. Overall crossover of ARM nodes with SLNs was determined in 36.5%. The ICG intensity was found to be higher in both hot and blue SLNS (8 out of 18 ICG positive cases, 44.4%). In 3 of 52 patients (5.7%) metastatic SLNs were hot or blue but fluorescent which predicts metastatic involvement of the ARM-nodes. More than 1-third of the patients revealed a crossover between arm and breast draining nodes. The higher observed rate of overlap might partially explain why more patients develop clinically significant lymphedema after NST even after sentinel lymph node biopsy alone. The triple mapping provides valuable data regarding the competency of lymphatic drainage and would have the potential to serve selecting patients for lymphovenous by-pass procedures at the index procedure. NST reduces the metastatic involvement of the ARM nodes. However, conservative axillary staging with sparing ARM nodes after NST necessitates further studies with larger sample size and longer follow-up.

Axillary reverse mapping using near-infrared fluorescence imaging in invasive breast cancer (ARMONIC study)

BackgroundAxillary lymph node dissection (ALND) in patients with breast cancer has potential side effects, including upper-limb lymphedema. Axillary reverse mapping (ARM) is a technique that enables discrimination of the lymphatic drainage of the upper limb in the axillary lymph node basin from that of the breast. We aimed to evaluate ARM node identification by near-infrared (NIR) fluorescence imaging during total mastectomy with ALND and then to analyze potential predictive factors of ARM node involvement. MethodsThe study enrolled 119 patients diagnosed with invasive breast cancer with an indication for ALND. NIR imaging using indocyanine green dye was performed in 109 patients during standard ALND to identify ARM nodes and their corresponding lymphatic ducts. Results94.5% of patients had ARM nodes identified (95%CI = [88.4–98.0]). The ARM nodes were localized in zone D in 63.4% of cases. Metastatic axillary lymph nodes were found in 55% in the whole cohort, and 19.4% also had metastasis in ARM nodes. Two patients had metastatic ARM nodes but not in the remaining axillary lymph nodes. No serious adverse events were observed. Only the amount of mitosis was significantly associated with ARM node metastasis. ConclusionsARM by NIR fluorescence imaging could be a reliable technique to identify ARM nodes in real-time when ALND is performed. The clinical data compared with ARM node histological diagnosis showed only the amount of mitosis in the diagnostic biopsy is a potential predictive factor of ARM node involvement. Clinical trial registrationNCT02994225.

Near-Infrared Fluorescence Axillary Reverse Mapping (ARM) Procedure in Invasive Breast Cancer: Relationship between Fluorescence Signal in ARM Lymph Nodes and Clinical Outcomes

Simple SummaryNear-infrared fluorescence axillary reverse mapping (ARM) is a promising procedure for identification and preservation of arm lymphatic drainage during axillary lymph node dissection (ALND). We included 109 patients to analyze the indocyanine green fluorescence signal in ARM lymph nodes after resection. The fluorescence signal from ARM lymph nodes were compared with clinical findings to determine the importance of this criterion on the potential management of patients with ALND. ARM lymph nodes were identified in 94.5% of cases. The mean normalized fluorescence signal intensity value was 0.47 with no significant signal difference between metastatic and non-metastatic ARM lymph nodes. Only the preoperative diagnosis of metastasis in the axillary nodes of patients was significantly associated with a higher ARM node fluorescence signal intensity. Although preliminary results did not show that fluorescence signal intensity is a reliable diagnostic tool, the NIR fluorescence ARM procedure may be useful for ARM lymph node identification.The near-infrared (NIR) fluorescence axillary reverse mapping (ARM) procedure is a promising tool to identify and preserve arm lymphatic drainage during axillary lymph node dissection (ALND). The ARMONIC clinical trial was conducted to validate the technique on a large cohort of patients and to analyze the predictive clinical factors for ARM lymph node metastasis. For the first time, the fluorescence signal intensity from the ARM lymph nodes was measured and correlated with clinical findings. A total of 109 patients with invasive breast cancer and indications of mastectomy and ALND underwent the NIR fluorescence ARM procedure. Indocyanine green was administered by intradermal injection followed by intraoperative identification and resection of the ARM lymph nodes with NIR fluorescence camera guidance. The fluorescence signal intensity and signal distribution were then measured ex vivo and compared with clinical outcomes. ARM lymph nodes were successfully identified by fluorescence in 94.5% of cases. The mean normalized fluorescence signal intensity value was 0.47 with no significant signal difference between metastatic and non-metastatic ARM lymph nodes (p = 0.3728). At the microscopic level, the fluorescence signal distribution was focally intense in lymphoid tissue areas. Only the preoperative diagnosis of metastasis in the axillary nodes of patients was significantly associated with a higher ARM node fluorescence signal intensity (p = 0.0253), though it was not significantly associated with the pathological nodal (pN) status (p = 0.8081). Based on an optimal cut-off fluorescence value, the final sensitivity and specificity of the NIR fluorescence ARM procedure for ARM lymph node metastatic involvement were 64.7% and 47.3%, respectively. Although our preliminary results did not show that fluorescence signal intensity is a reliable diagnostic tool, the NIR fluorescence ARM procedure may be useful for ARM lymph node identification. Clinical trial registration: NCT02994225.

Application of Fluorescence Dye in Combination with Methylene Blue for Axillary Reverse Mapping in Patients with Modified Radical Mastectomy for Breast Cancer.

Background Axillary reverse mapping (ARM) is a novel intraoperative technique developed in recent years. This study was aimed at determining the effect of combined use of fluorescence dye and methylene blue, as well as its feasibility of ARM in patients with breast cancers who undergo modified radical mastectomy. Method From January 2016 to June 2017, 46 patients with primary breast cancer at stage I-IV (Tis-T3, N0-N3, and M0) who received modified radical mastectomy were enrolled in this study. The exclusion criteria included preoperative radiotherapy/chemotherapy or bilateral disease. Patients were divided into 2 groups: methylene blue group (22 patients, 47.8%) and methylene blue+indocyanine green (ICG) group (24 patients, 52.2%). ARM was performed before surgery. Results The overall visualization rate of ARM nodes was 80.4% (37/46). The visualization rate was significantly increased in methylene blue+ICG group (91.67%, 22/24) than that in methylene blue group (63.64%, 14/22) (P = 0.032). There was a statistical difference of visualization rate between clinical groups of N0-N1 and N3-N4 (t = 2.431, P = 0.19 < 0.05). Although there was no significant difference found in the total drainage volume and arm perimeter of patients between the two groups (P > 0.05), the harden diameter of the injection site in methylene blue+ICG group was significantly longer than that in methylene blue group (P < 0.05). Among the 44 patients with different molecular profiling of breast cancer, there was no significant difference of visualization rate of ARM nodes in luminal A group (100%,5/5), luminal B group (75.0%, 18/24, P = 0.21), HER2 group (75.0%, 6/8, P = 0.22), and basal-like group (85.7%, 6/7, P = 0.37). Conclusions ARM using methylene blue+ICG presented greater identification rate than that with methylene blue alone, especially in patients with more invasive breast cancer. Our finding offers support for the improvement of ARM in future breast cancer management.

Utility of Axillary Reverse Mapping (ARM) and Incidence of Metastasis in Arm Draining Lymph Nodes in Patients with Breast Cancer.

Objective Lymphedema of the upper limb is the most common complication in patients with breast cancer, who require axillary lymph node (LN) dissection. Proposition of identifying upper limb draining LN and preserving it, during axillary dissection can reduce significant postoperative morbidity, but it has the risk of inadequate oncological resection. This study was planned to find out metastatic rate in axillary reverse mapping (ARM) nodes in our population. Materials and Methods Lymphoscintigraphy (LSG) was performed using intradermal injection of 99m Tc Sulfur Colloid into ipsilateral second and third interdigital web spaces of hand in patients with breast cancer. Planar, single-photon emission computed tomography-computed tomography images were acquired followed by intraoperative localization of arm draining LNs using Gamma Probe. All identified ARM nodes were dissected and sent for histopathological examination to confirm metastatic involvement. Results Twenty eligible patients were prospectively analyzed. The identification rate of arm draining LN with LSG was 90% (18/20). Among 14 eligible patients included in the study, ARM node metastasis was seen in two patients. A total of 64 ARM nodes were dissected from 14 patients, 4/64 nodes (2 patients) were positive for metastases (6.25%). Of the six patients excluded from the study, in 1 patient ARM node could not be identified on Gamma Probe, in two cases, it could not be retrieved surgically, in next two cases ARM could not be identified on LSG and remaining one case was removed because of previous surgical intervention. Conclusion In the current study, LSG showed the identification rate of 90% for ARM nodes in patients with carcinoma breast and metastatic involvement was seen in 6.25% (4/64) of these nodes in 2/14 (14.2%) patients, which is in agreement with previously published data. Oncological safety of preserving ARM nodes needs to be evaluated in the larger population.

Abstract P1-01-02: Pathologic nodal status is a predictor for metastatic disease in lymph nodes identified by axillary reverse mapping

Abstract Background Breast cancer is the most common cancer in female patients worldwide. Although axillary management in breast cancer has been de-escalated to reduce untoward effects, breast cancer-related lymphedema (BCRL) is still not uncommon. Axillary reverse mapping (ARM) emerges as a novel technique that identifies the lymphatic system draining the upper extremities. Preservation of this system and associated lymph nodes theoretically reduces the chance of BCRL. However, concerns regarding oncologic safety have limited the adoption of the technique. Objective To identify factors associated with metastatic disease in lymph nodes identified by ARM in breast cancer patients. Materials and methods Breast cancer patients treated at King Chulalongkorn Memorial Hospital from October 2018 to January 2021 who underwent axillary lymph node dissection (ALND) underwent concurrent ARM whereby five milliliters of 1% isosulfan blue dye was injected at the medial aspect of the arm as previously described elsewhere. Patient demographics and clinical data such as clinical staging, pathological staging, cancer subtype, and whether neoadjuvant chemotherapy was administered were collected and analyzed. Result Thirty-six patients with a median age of 57 were included in this prospective study. ARM lymph node identification success rate was 83% (30 of 36 patients) with a median of 2 identified ARM lymph nodes (range 0-11 nodes). Metastatic disease in ARM nodes was present in 30% of patients. ARM success rate did not depend on whether preoperative chemotherapy had been given (ARM lymph nodes identified in 7 out of 8 patients without preoperative chemotherapy and 23 out of 28 in patients with preoperative chemotherapy; p=0.36). There was no statistically significant difference in metastatic disease in ARM-identified nodes and clinical stage (stage II=13.3%, stage III=33.3%, and stage IV=50.0%; p=0.18). However, higher pathologic N stage was associated with finding metastasis in ARM-identified lymph nodes (N0=0%, N1=15.8%, N2=33.3%, and N3=80%; p=0.005). Conclusions ARM is a novel technique which can potentially reduce BCRL. However, a significant number of ARM lymph nodes were found to have pathologically-proven metastatic disease, especially in higher pathologic N stages (pN2 and pN3). Therefore, for oncologic safety, consideration should be given to removal of all ARM lymph nodes in breast cancer patients undergoing formal axillary dissection. Keywords: Axillary Reverse Mapping, Axillar dissection, Lymphedema, Breast Cancer Citation Format: Rak Saengphongchawan, Sopark Manasnayakorn. Pathologic nodal status is a predictor for metastatic disease in lymph nodes identified by axillary reverse mapping [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 P1-01-02.

Preventing Breast Cancer-Related Lymphedema: Feasibility of Axillary Reverse Mapping Technique

Introduction. Our study aimed to determine the feasibility of axillary reverse mapping (ARM) technique, the identification rate of ARM nodes and their metastatic involvement, as well as to identify the factors that influence the identification and metastatic involvement. Material and methods. In total, 30 breast cancer patients scheduled for axillary lymph node dissection were enrolled in our study. The lymphatic nodes that drain the arm were identified by injecting 1 mL of blue dye in the ipsilateral upper arm; then, the ARM nodes were resected along with the other lymph nodes and sent for histological evaluation. Results. Identification of ARM node was successful in 18 patients (60%) and 22.22% of the identified ARM lymph nodes had metastatic involvement. Patients with identified ARM nodes had a significant lower BMI and a statistically significant relationship between axillary lymph node status and ARM node metastases was proven. Most of ARM lymph nodes (96.3%) were found above the intercostobrachial nerve, under the axillary vein and lateral to the thoracodorsal bundle. Conclusions. The ARM procedure is easy to reproduce but might not be appropriate for patients with a high BMI. The rate of metastatic involvement of ARM nodes is significant and no factor can predict it, showing that the preservation of these nodes cannot be considered.

The involvement of axillary reverse mapping nodes in patients with clinically node-negative breast cancer.

Axillary reverse mapping (ARM) was developed to preserve the lymphatic drainage from the upper arm during sentinel lymph-node (SLN) biopsy or axillary lymph-node dissection (ALND). However, the oncological safety of ARM has been controversial because of not infrequent involvement of ARM nodes. Patients with clinically negative nodes (cN0) underwent SLN biopsy and ARM. SLNs were identified using blue dye and radioisotope, and ARM nodes were traced using the fluorescent method. Patients with positive SLN underwent the standard ALND. After surgery, they were followed up for more than 3 years. A total of 507 patients with cN0 breast cancer were enrolled between May 2009 and November 2017. SLNs were identified in 499 (98%) of 507 patients, and ARM nodes were identified in 159 (31%) patients in the SLN field. The crossover rate of SLN-ARM nodes was 28%. Among 95 patients with positive SLNs, 70 patients underwent conventional ALND. ARM nodes were identified in 65 (93%) of those patients in the ALND field. The mean number of removed ARM nodes was 7.2 (range 0-25) in patients who underwent the standard ALND. Although ARM nodes were involved in 18 of 65 patients, the involved ARM nodes were the same SLNs identified in 14 (78%) patients. Since SLN-ARM nodes should be removed, ARM nodes were involved only in 4 (5.7%) patients after SLN biopsy. Except for positive SLN-ARM nodes, the involvement of ARM nodes is infrequent in patients with positive SLN.

Axillary Reverse Mapping in Patients Undergoing Axillary Lymph Node Dissection: A Single Institution Experience From India

IntroductionAxillary lymph node dissection (ALND) remains the gold standard for clinically node-positive and sentinel node biopsy (SLNB) positive breast cancer patients, but it is associated with the debilitating morbidity of lymphedema. Recently, a new technique of axillary reverse mapping (ARM) has been described which helps in differentiating arm lymphatics from breast lymphatics.AimTo evaluate the applicability of the ARM technique with blue dye and the incidence of metastases in ARM nodes in the Indian population.MethodA total of 120 patients underwent ARM during ALND. Blue lymphatic channels and lymph nodes were noted. All axillary nodes along with ARM nodes were dissected and sent separately for pathological evaluation for metastases.ResultsARM nodes or lymphatics were identified in 65 (54.17%) out of 120 patients. The mean ARM lymph node yield was 1.4. The patients in whom ARM lymph nodes or lymphatics were not identified had significantly higher T stage and N stage (p <0.00001) than in whom it was identified. There was no significant correlation between ARM identification with BMI, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2/neu), and neoadjuvant chemotherapy (NACT) status. ARM nodes were found metastatic in three patients (7.5%). All these patients had clinically N2 disease and all had pathologically more than ten nodes involved in the axilla.ConclusionThe identification rate of ARM nodes and lymphatics with blue dye is lower in Indian patients who present with higher clinical T and N stage disease. Other clinicopathological parameters were not associated with the identification rate. The rate of metastasis in ARM nodes is high in patients with a high axillary tumor burden. Hence, preserving ARM nodes may not be oncologically safe in higher N stage disease.

The role of axillary reverse mapping in intraoperative nodal palpation during sentinel lymph node biopsy.

Intraoperative nodal palpation in the axilla is a mandatory part of sentinel lymph node biopsy. However, there is no consensus regarding the definition of suspicious palpable node. The sampling rate and involvement rate of suspicious palpable nodes are inconsistent. We hypothesized that axillary reverse mapping is helpful to select suspicious palpable sentinel lymph nodes more accurately. Patients with clinically negative nodes underwent sentinel lymph node biopsy with intraoperative nodal palpation and axillary reverse mapping. Blue and hot nodes were removed as sentinel lymph nodes. Suspicious palpable nodes that were neither blue nor hot were removed as palpable sentinel lymph nodes. Nodes around blue and hot sentinel lymph node were incidentally removed as para-sentinel lymph nodes. Fluorescent nodes were considered axillary reverse mapping nodes. Patients with positive sentinel lymph node underwent axillary lymph node dissection. Palpable sentinel lymph nodes and para-sentinel lymph nodes were removed in 130 (15%) of 850 patients with clinically negative nodes. Although palpable sentinel lymph nodes and para-sentinel lymph nodes were involved in 19 (15%) of 130 patients, fluorescent palpable sentinel lymph nodes were involved only in 2 patients and fluorescent para-sentinel lymph nodes were not involved. When excluding fluorescent palpable sentinel lymph nodes and para-sentinel lymph nodes, the sampling rate of suspicious palpable nodes significantly decreased (15% vs. 5%, p<0.01) and the involvement rate of palpable sentinel lymph nodes significantly increased (15% vs. 31%, p<0.05). Axillary reverse mapping is helpful to avoid an unnecessary removal of palpable nodes without metastases.

83P Axillary reverse mapping using near-infrared fluorescence imaging in invasive breast cancer (ARMONIC study)

Axillary lymph node dissection (ALND) in patients with breast cancer has the potential to induce side effects, including upper-limb lymphedema. Axillary reverse mapping (ARM) is a technique that enables discrimination of the lymphatic drainage of the breast from that of the upper limb in the axillary lymph node (LN) basin. We aimed to determine ARM node identification rate by near-infrared (NIR) fluorescence imaging during total mastectomy with ALND and then to analyze potential predictive factors of ARM node involvement.

Comparison of indocyanine green and methylene blue use for axillary reverse mapping during axillary lymph node dissection.

Axillary reverse mapping (ARM) is a technique to identify arm lymphatic drainage during axillary lymph node dissection (ALND). This study compared the feasibility of ARM using indocyanine green (ICG) or methylene blue (MB), and accessed the oncologic safety of the procedure. Overall, 158 patients qualified for ALND were enrolled. The characteristics of ARM‐identified nodes were recorded with ICG (n = 78) or MB (n = 80) visualization. Fine‐needle aspiration cytology (FNAC) of the nodes were performed and validated by histologic analysis. The nodal identification rate in the ICG group significantly surpassed that of the MB group (87.2% vs 52.5%, P < .05) with fewer complications. Note that 10.9% of the patients had metastatic involvement of the ARM‐identified nodes. Also 80% of the positive nodes were found in areas B and D, while the ARM‐identified nodes mainly located in area A. All the 51 nodes diagnosed as negative of malignancy by FNAC were free of metastasis. Nodal metastasis was significantly correlated with extensive nodel involvement, advanced disease, and the characteristics of identified nodes. In conclusion, ICG appears superior to MB for ARM nodes identification. FNAC, together with the features of primary tumors and ARM nodes, can delineate which nodes could be preserved during ALND.

Using the axillary reverse mapping technique to screen breast cancer patients with a high risk of lymphedema

BackgroundPreventing breast cancer-related lymphedema (BCRL) by preserving upper lymphatic drainage is still controversial. Our study aimed to use the axillary reverse mapping (ARM) technique in patients who underwent axillary surgery to analyse the correlation between postoperative residual ARM nodes and the occurrence of lymphedema, select candidates at high risk of developing lymphedema, and analyse the oncologic safety of ARM nodes.MethodsPatients undergoing sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) from October 2015 to February 2016 at the Peking University People’s Hospital Breast Center were prospectively recruited for the study. ARM was performed in all patients before surgery. ARM nodes were separated from SLNB and ALND specimens. Data were collected on the identification of ARM nodes before surgery, number of residual ARM nodes after surgery, nodal status, crossover rate, and correlation between residual ARM nodes and the occurrence of lymphedema.ResultsThe analysis included 78 patients. Of the 53 patients who underwent SLNB, crossover between ARM nodes and breast sentinel lymph nodes (SLNs) was seen in 22 specimens. The incidence of ARM node metastasis was 1.89% (1/53) and 25% (9/36) in the SLNB and ALND groups, respectively. The number of positive axillary lymph nodes was associated with the involvement of ARM nodes (P = 0.036). The incidence of residual ARM nodes was significantly higher in the SLNB group than in the ALND group (67.6% vs. 37.9%, P = 0.016). The incidence of lymphedema was significantly higher in the ALND group than in the SLNB group (33.3% vs. 5.4%, P = 0.003).ConclusionsFor SLNB, the ARM technique can help to resect SLNs more accurately. However, we do not recommend using the ARM technique to preserve ARM nodes in patients undergoing ALND due to oncologic safety issues. Nevertheless, we can predict patients undergoing axillary surgery who are more likely to have a high risk of lymphedema by assessing residual ARM nodes.Trial registrationThis study was registered on ClinicalTrials.gov in February 2016.The clinical trial registration number is NCT02691624.

Conserving the lymphatics from the arm using fluorescence imaging in patients with breast cancer at high risk of postoperative lymphedema: a pilot study.

Postoperative lymphedema in breast cancer survivors is a serious complication that develops from axillary lymph node dissection (ALND), chemotherapy, and radiation therapy. Axillary reverse mapping (ARM) was recently introduced to reduce lymphedema. This pilot study aimed to investigate the feasibility of preserving the ARM node using fluorescence imaging for patients at high risk of lymphedema. We prospectively screened patients with breast cancer who had pathologic node-positive disease at diagnosis and were scheduled for neoadjuvant chemotherapy (NCT). The sentinel lymph node (SLN) was identified using blue dye and radioisotope, while the ARM node was traced using indocyanine green (ICG). In cases in which SLN was negative on the intraoperative frozen section examination, the ARM node and lymphatics were preserved. Of the 20 screened patients, six whose metastatic axillary lymph node (ALN) was converted to clinically node-negative disease after NCT were enrolled. No patients experienced recurrence at 24 months postoperative. Four patients who had a preserved ARM node did not develop lymphedema. One patient whose ARM node was not preserved due to SLN identification failure did not develop postoperative lymphedema. One patient who underwent ALND without ARM node conservation because of metastatic SLN on frozen section examination developed postoperative lymphedema. ARM is oncologically safe, decreases the incidence of postoperative lymphedema, and allows for the early detection of postoperative lymphedema in patients who underwent ALND. Ultimately, ARM may help improve the quality of life of patients with pathologic node-positive breast cancer.

Relationship between Upper Extremity Lymphatic Drainage and Sentinel Lymph Nodes in Patients with Breast Cancer

Purpose The purpose of this study was to identify the relationship between upper extremity lymphatics and sentinel lymph nodes (SLNs) in breast cancer patients. Methods Forty-four patients who underwent axillary reverse mapping (ARM) during axillary lymph node dissection (ALND) with SNL biopsy (SLNB) between February 2017 and October 2017 were investigated. ARM was performed using indocyanine green (ICG) to locate the upper extremity lymphatics; methylene blue dye was injected intradermally for SLN mapping. Results ARM nodes were found in the ALND fields of all examined patients. The rate of identification of upper extremity lymphatics within the SLNB field was 65.9% (29 of 44). The ARM nodes were involved in metastases arising from primary breast tumors in 7 of the patients (15.9%), while no metastases were detected in pathologic axillary lymph node-negative patients. Lymphatics from the upper extremity drained into the SLNs in 5 of the 44 patients (11.4%); their ARM-detected nodes were found to be in close proximity to the SLNs. Conclusions The ARM nodes and SLNs are closely related and share lymphatic drainage routes. The ARM procedure using fluorescence imaging is both feasible and, in patients who are SLN negative, oncologically safe. ARM using ICG is therefore effective for identifying and preserving upper extremity lymphatics, and SLNB combined with ARM appears to be a promising surgical refinement for preventing upper extremity lymphoedema. Clinical Trial Registration This trial is registered with ClinicalTrial.gov: NCT02651142.

Location of arm draining lymph node in relation to breast cancer radiotherapy field and target volume

BackgroundLymphoedema of the arm following axillary surgery or radiotherapy remains a significant side effect affecting some women after breast cancer treatment. Axillary reverse mapping (ARM) is a technique used to identify the lymph node draining the arm (ARM node). Our study aim was to examine the location of the ARM nodes in relation to target volumes and treatment fields for breast cancer radiotherapy. Materials and methodsEighteen breast cancer patients underwent lymphoscintigraphy of contralateral arm (left 10, right 8) and SPECT CT scan on a research study. Patient position for the SPECT CT scan approximated the position used for radiotherapy. Using MIM software™, the ARM node for each subject was contoured on the SPECT CT and verified by a nuclear medicine physician. The CT component of the SPECT CT was then transferred to ECLIPSE™ radiotherapy planning software, and the contralateral breast and axilla were contoured on this CT scan according to the ESTRO contouring guideline. Two radiotherapy plans were generated for each subject using standard tangential IMRT technique at a dose of 50 Gy in 25 fractions, one treating contralateral breast alone, the other treating contralateral breast and contralateral axilla level 1–4. The ARM node was considered “within the radiotherapy field” if the mean dose received by the ARM node was more than 50% of the prescribed dose: i.e., 25 Gy. ResultsOne right-sided subject had 2 ARM nodes, all others had 1 ARM node. All ARM nodes (left 10, right 9) were located within level 1 of the axilla. For the subject with 2 ARM nodes, the node that received a higher dose was used for the analysis. The mean dose received by the ARM node in the whole breast radiotherapy plans ranged from 0.8 to 45.5 Gy, with a median of 10.9 Gy. The mean dose received by the ARM node in the whole breast and axilla plans ranged from 43.4 to 52.5 Gy, with a median of 49.3 Gy. In the whole breast radiotherapy plans, only 5 out of 18 ARM nodes were found to be “within radiotherapy field”, and only 2 ARM nodes received more than 40 Gy. In the breast and axilla plans, all 18 ARM nodes were “within radiotherapy field” and all received more than 40 Gy. To better visualise the locations of ARM nodes, all left sided ARM nodes were then mapped onto a CT set from one of the left-sided subjects, and all the right sided ARM nodes mapped onto one of the right-sided subjects, and digitally reconstructed radiograph (DRR) for radiotherapy fields were produced. ConclusionsOur study demonstrates that the vast majority of ARM nodes (72%) are outside the tangential whole breast radiotherapy fields. In our study, all the ARM nodes were within the axillary radiotherapy fields covering level 1–4 axillary volumes according to the ESTRO contouring guideline, and complete shielding of the humeral head according to the EORTC consensus did not lead to sparing of the ARM nodes. A prospective study is needed to examine the oncological safety of ARM node-sparing axillary radiotherapy and its potential to reduce the risk of arm lymphoedema.

Abstract P2-01-39: Axillary reverse mapping using fluorescence imaging in the surgical treatment for breast cancer patients

Abstract Background: Axillary lymph node dissection (ALND) is the standard surgical treatment for breast cancer patients who have axillary nodal metastasis but do not meet the criteria of Z0011 trial. Arm lymphedema is one of the most common and serious complications of ALND. Based on the hypothesis that the lymphatic system of the upper extremity may be separate from that of the breast, the axillary reverse mapping (ARM) technique has been developed to identify the axillary lymph nodes and lymphatics that receive the lymph from the upper limb, and to preserve them during ALND in order to prevent arm lymphedema. However, it is difficult to keep the arm lymphatic system intact because of the lack of full understanding of anatomical variations of the ARM nodes and lymphatics in the axilla, the inconsistency of different ARM techniques in identifying the axillary ARM nodes, and the potentially high rate of ARM nodal metastases in breast cancer patients. The aims of this study was to know (1) the identification rate of ARM with fluorescence imaging (2) the distribution of these ARM nodes and (3) whether it's safe to spare the ARM nodes in breast cancer patients during SLNB or ALND. Method: Forty female patients of primary invasive breast cancer between 28 to 69 years old were included in the prospective study. Patients who had bilateral breast cancer, the history of axillary surgery, or the history of neoadjuvant chemotherapy were excluded. Methylene blue dye was used in the SLNB procedure. The ARM procedure was carried out to all the patients with a subcutaneous injection of the fluorescent dye indocyanine green into the medial bicipital sulcus in the upper arm about 15 minutes before SLNB or ALND. During surgery, photodynamic eye was used to detect the fluorescent nodes in the axilla. The fluorescent ARM nodes in the surgical region were removed and sent for pathological examination of node metastasis. Results: ARM was successful in 8 out of the 35 patients who underwent SLNB + ARM, in 3 out of the 5 patients who underwent ALND + ARM and in 25 out of the 35 patients who underwent ALND following SLNB + ARM. The ARM identification rate was 22.9%(8/35) in SLNB, and was 93.3%(28/30) in ALND. Totally, 119 fluorescent ARM nodes were detected, and 57.1 % (68/119) of them were located under the axillary vein, above the 2nd intercostobrachial nerve, and in the lateral of thoracic dorsal neurovascular bundle. Six out of 35 patients were found to have ARM-SLN crossover during SLNB+ARM procedure. Two out of 24 patients were found to have the ARM nodal metastases, with the pathological node stage being pN2, pN3 respectively. Conclusion: ARM with fluorescence imaging using indocyanine green was sensitive for identification of ARM nodes in ALND with a high success rate; ARM nodes had a certain distribution pattern in the axilla; ARM should not be performed to the patients with multiple nodal metastases in the axilla. Citation Format: Liu J, Li J, Zhou J, Cui H, Xiang J, Jia P, Xiang A, Chen H. Axillary reverse mapping using fluorescence imaging in the surgical treatment for breast cancer patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-01-39.

Feasibility of Axillary Reverse Mapping and Clinicopathological Features Predicting ARM Node Metastasis in Breast Cancer-a Pilot Study.

The axillary reverse mapping (ARM) technique has been described as an attempt to map and preserve the upper extremity lymphatic drainage during axillary lymph node dissection (ALND) and/or SLNB. This technique is based on the hypothesis that the lymphatic pathway from the upper extremity is not involved by metastasis from primary breast cancer. The ARM node/s however, has been found, in various studies, to be involved with metastatic foci in patients with extensive axillary lymph node metastases. Therefore, the oncological safety of this procedure has not yet been determined. In this pilot study, we assessed the ARM node intraoperatively for various parameters and compared it to final HPR, to try and determine the oncologic safety of preserving the ARM node. Seventy-two breast cancer patients were screened for this prospective pilot study which was planned to recruit 20 patients. The study was initiated on May 2014, 20 patients were recruited till July 2015. Eligibility criterion was as follows: patients requiring primary axillary lymph node dissection based on a clinically positive axilla. Forty-five patients were ineligible because they had either received neoadjuvant chemotherapy or underwent previous axillary surgery or axillary radiation (exclusion criteria). Seven patients refused to give consent. ARM node identification rate was 75%. The most common location of the ARM node was lateral to the latissimus dorsi pedicle (42.10%), none of them being malignant. None of the oval or firm nodes were malignant. Tumor deposits were identified in 13%. Fine-needle aspiration cytology (FNAC) had 100% specificity, 94.4% negative predictive value, 100% positive predictive value, and 50% sensitivity. ARM is feasible using blue dye alone, with an acceptable identification rate. Location, consistency, and intraoperative FNAC of the ARM node, put together, may be reliable parameters to predict involvement of the ARM node with metastasis.