Marked Node Research Articles

Targeted axillary dissection using carbon marking for patients with node-positive breast cancer following neoadjuvant therapy (TADCOM): study protocol for a prospective, multicenter, randomized controlled trial

BackgroundNeoadjuvant chemotherapy (NAC) for breast cancer enables pathological complete response (pCR) in patients initially diagnosed with axillary lymph node metastases, potentially obviating the need for axillary lymph node dissection (ALND). Current targeted axillary dissection (TAD) techniques, guided by traditional tissue markers placed prior to NAC, face challenges such as marker loss and high costs. Carbon nanoparticle suspension injection (CNSI) offers a stable and reliable alternative for marking, which could enhance the TAD procedure. This study aims to evaluate the feasibility and accuracy of different TAD strategies using CNSIs and to explore their clinical utility in locally advanced breast cancer.MethodsThis prospective, multicenter, randomized controlled trial will enroll 126 biopsy-proven breast cancer patients with suspicious axillary lymph node metastases (cN1-2a) who achieve ycN0 status following NAC. Participants will be randomized in a 1:1:1 ratio to undergo TAD guided by: [1] conventional tissue clips (CG-TAD); [2] CNSI lymph node marking (CN-LNM); or [3] peritumoral CNSI mapping (PCN-MAP). Primary endpoints include retrieval rate of marked lymph nodes, number of sentinel and marked lymph nodes, concordance rates, and complication rates. Secondary endpoints encompass regional and distant recurrence rates, survival outcomes, surgical duration, postoperative complications, quality of life scores, and margin status in breast-conserving surgery. Statistical analyses will adhere strictly to the CONSORT guidelines.DiscussionThis study aims to evaluate the feasibility and accuracy of CNSI for targeted axillary dissection in breast cancer patients following neoadjuvant chemotherapy and to explore its clinical significance in reducing surgical complications and costs, as well as improving surgical precision.Trial registrationClinicaltrials.gov, NCT04744506, Registered 27 December 2020, Updated 24 September 2024. Protocol Version Ver 1.2, 17/9/2024.

The feasibility of targeted axillary dissection for breast cancer axillary surgery de-escalation after neoadjuvant therapy: A prospective cohort study.

Targeted axillary dissection (TAD) after neoadjuvant therapy (NAT) includes removing of marked and sentinel lymph nodes (SLNs). The aim was to investigate the optimization of TAD localization techniques after NAT among breast cancer patients. From November 2020 to 2022, we prospectively enrolled 107 lymph node-positive breast cancer patients in XX Hospital and received complete cycles of NAT. Patients were randomly divided into the following 3 groups before treatment: group A, marked node with clip (n=34); group B, marked node with 125I seed (n=32); and group C, marked node with clip and 125I seed (n=41). Dual tracers were used to search for SLNs after NAT. The main endpoint was the detection rate of marked nodes and false-negative rate (FNR). The detection rates using the TAD localization technique were 82.6% (28/34), 100% (32/32), and 100% (41/41) for groups A, B, and C, respectively (P>0.05). The FNR rates were 15.8%, 5.9%, and 5.6% among group A, B, and C, respectively (P>0.05). The FNR rates in cN1 patients were 5.1%, 2.7%, and 2.6%, among these three groups, respectively (P>0.05). The change in distance between 125I seeds and clips in axillary lymph nodes was <3mm. The FNR rates of TAD guided by dye tracer, radiolabeled tracer, and dual tracers were 5.4%, 5.2%, and 3.4%, respectively (P>0.05). The negative predictive values were 93.0%, 93.0%, and 95.2%, respectively (P>0.05). Considering inexpensive and detect rate of 125I seeds, it is recommended that placement of 125I seeds to localize metastatic nodes in neoadjuvant setting. The TAD guided by dye tracer is also feasible for axillary de-escalation surgery after NAT in countries or regions without radiolabeled colloid.

Mathematical analysis of human motion vision capture image processing based on artificial intelligence

In order to understand the mathematical analysis of human motion vision capture image processing, a mathematical analysis of human motion vision capture image processing based on artificial intelligence is proposed. This paper firstly introduces the research progress, classification and several commonly used vision-based human motion tracking methods of motion capture technology. Secondly, the process and framework of capturing human motion video by using ordinary cameras and marking nodes are proposed, and the automatic tracking algorithm based on Camshift and Kalman filter is adopted. It verifies the effectiveness of the system, changes the traditional way of motion capture, and makes the process of capture more convenient when the capture effect meets the requirements. Finally, the performance of the human motion capture data retrieval algorithm based on video is evaluated comprehensively. It is compared with the latest literature in this field. In terms of time efficiency, for each online retrieval of data set, the proposed algorithm takes 0.056 s, while the methods of other scholars take an average of 1.5 s. Meanwhile, experiments are also conducted on public databases, proving the universality and scalability of the proposed algorithm. The algorithm proposed in this paper has greater advantages than the most advanced method of the same type, which verifies the effectiveness of the algorithm proposed in this paper.

Disección axilar dirigida tras tratamiento sistémico primario en cáncer de mama N1. Validación de la técnica y experiencia a los 4 años

ObjectivesTo assess the omission of systematic axillary lymphadenectomy (ALND) in patients with N1 breast cancer with axillary pathological response (APR) after primary systemic treatment (PST). Description and experience of the Technique: Target Axillary Dissection TAD. Identify which subtypes are associated with higher APR. Patients and methodsA descriptive, retrospective study of 90 patients with cT1-T3/N1/M0 stage breast carcinoma who received TSP at the Valencian Institute of Oncology (IVO), between January 2020 and December 2023; 63 received chemotherapy and/or anti-HER2 therapy and 27 received hormonal therapy. Biopsy and labeling of the suspicious lymph node (maximum 3) were performed. In the surgery, a harpoon was placed in the axillary lymph node and the sentinel lymph node (BSGC) technique was also performed with technetium-99m and methylene blue. ResultsAPR was achieved in 46/90 cases (51.2%), in 30/46 (65.2%) pCR, and in 16/46 ITC (isolated tumor cells) or micrometastases remained. Macrometastases were observed in 44/90 (48.8%) and therefore ALND or axillary Rt was performed. There have been no axillary or distant relapses. Detection of the marked node: 100%. RPA occurred in: Luminal A, 26%; Luminal B, 42%; HER2-positive, 86% and Triple Negative, 66%. ConclusionsIn the IVO, ADT is a feasible technique. More than 50% of the cohort had an APR avoiding ALND. The HER2-positive and triple negative subtypes have the highest response rate. It is an oncologically safe procedure; NOT less than ALND.

Wire-Free Targeted Axillary Dissection: A Pooled Analysis of 1300+ Cases Post-Neoadjuvant Systemic Therapy in Node-Positive Early Breast Cancer.

Recent advances in neoadjuvant systemic therapy (NST) have significantly improved pathologic complete response rates in early breast cancer, challenging the role of axillary lymph node dissection in nose-positive patients. Targeted axillary dissection (TAD) integrates marked lymph node biopsy (MLNB) and tracer-guided sentinel lymph node biopsy (SLNB). The introduction of new wire-free localisation markers (LMs) has streamlined TAD and increased its adoption. The primary endpoints include the successful localisation and retrieval rates of LMs. The secondary endpoints include the pathological complete response (pCR), SLNB, and MLNB concordance, as well as false-negative rates. Seventeen studies encompassing 1358 TAD procedures in 1355 met the inclusion criteria. The localisation and retrieval rate of LMs were 97% and 99%. A concordance rate of 67% (95% CI: 64-70) between SLNB and MLNB was demonstrated. Notably, 49 days (range: 0-272) was the average LM deployment time to surgery. pCR was observed in 46% (95% CI: 43-49) of cases, with no significant procedure-related complications. Omitting MLNB or SLNB would have under-staged the axilla in 15.2% or 5.4% (p = 0.0001) of cases, respectively. MLNB inclusion in axillary staging post-NST for initially node-positive patients is crucial. The radiation-free Savi Scout, with its minimal MRI artefacts, is the preferred technology for TAD.

Assessing the Efficacy of Radioactive Iodine Seed Localisation in Targeted Axillary Dissection for Node-Positive Early Breast Cancer Patients Undergoing Neoadjuvant Systemic Therapy: A Systematic Review and Pooled Analysis.

Targeted axillary dissection (TAD), employing marked lymph node biopsy (MLNB) alongside sentinel lymph node biopsy (SLNB), is increasingly recognised for its efficacy in reducing false negative rates (FNRs) in node-positive early breast cancer patients receiving neoadjuvant systemic therapy (NST). One such method, 125I radioactive seed localisation (RSL), involves implanting a seed into a biopsy-proven lymph node either pre- or post-NST. This systematic review and pooled analysis aimed to assess the performance of RSL in TAD among node-positive patients undergoing NST. Six studies, encompassing 574 TAD procedures, met the inclusion criteria. Results showed a 100% successful deployment rate, with a 97.6% successful localisation rate and a 99.8% retrieval rate. Additionally, there was a 60.0% concordance rate between SLNB and MLNB. The FNR of SLNB alone was significantly higher than it was for MLNB (18.8% versus 5.3%, respectively; p = 0.001). Pathological complete response (pCR) was observed in 44% of cases (248/564). On average, the interval from 125I seed deployment to surgery was 75.8 days (range: 0-272). These findings underscore the efficacy of RSL in TAD for node-positive patients undergoing NST, enabling precise axillary pCR identification and facilitating the safe omission of axillary lymph node dissection.

Evaluating Magnetic Seed Localization in Targeted Axillary Dissection for Node-Positive Early Breast Cancer Patients Receiving Neoadjuvant Systemic Therapy: A Comprehensive Review and Pooled Analysis.

Background/Objectives: De-escalation of axillary surgery is made possible by advancements in both neoadjuvant systemic therapy (NST) and in localisation technology for breast lesions. Magseed®, developed in 2013 by Dr. Michael Douk of Cambridge, United Kingdom, is a wire-free localisation technology that facilitates the localisation and retrieval of lymph nodes for staging. Targeted axillary dissection (TAD), which entails marked lymph node biopsy (MLNB) and sentinel lymph node biopsy (SLNB), has emerged as the preferred method to assess residual disease in post-NST node-positive patients. This systematic review and pooled analysis evaluate the performance of Magseed® in TAD. Methods: The search was carried out in PubMed and Google Scholar. An assessment of localisation, retrieval rates, concordance between MLNB and SLNB, and pathological complete response (pCR) in clinically node-positive patients post NST was undertaken. Results: Nine studies spanning 494 patients and 497 procedures were identified, with a 100% successful deployment rate, a 94.2% (468/497) [95% confidence interval (CI), 93.7-94.7] localisation rate, a 98.8% (491/497) retrieval rate, and a 68.8% (247/359) [95% CI 65.6-72.0] concordance rate. pCR was observed in 47.9% (220/459) ) [95% CI 43.3-52.6] of cases. Subgroup analysis of studies reporting the pathological status of MLNB and SLNB separately revealed an FNR of 4.2% for MLNB and 17.6% for SLNB (p = 0.0013). Mean duration of implantation was 37 days (range: 0-188). Conclusions: These findings highlight magnetic seed localisation's efficacy in TAD for NST-treated node-positive patients, aiding in accurate axillary pCR identification and safe de-escalation of axillary surgery in excellent responders.

Abstract PO2-23-05: Practice patterns and outcomes in the ongoing neoadjuvant ATNEC trial: node marking, response to NACT and breast conservation rates

Abstract Background In ATNEC trial, cT1-3N1M0 patients receive NACT followed by SNB/TAD. If the sentinel nodes(SNs) have converted to benign(ypN0), patients are randomly assigned to Axillary Treatment vs no Axillary Treatment. The study promotes standardized node marking procedures and includes a radiotherapy quality assurance program. Objectives – This study prospectively evaluates practice patterns, NACT response, adoption of node marking, rates of marked node identification, and breast conservation rates in the ongoing ATNEC trial across 70 centers in the UK. The trial aims to recruit 1900 patients. Materials and Methods Data from 196 randomized patients (median age: 54 [range: 28-79] years; median BMI: 26.5 [range: 17.6-51.1]) from December 2021 to June 28, 2023, across 70 UK centers were analyzed. These patients presented with cT1-3N1M0 breast cancer, received NACT, and exhibited no residual nodal disease (ypN0) on SNB/TAD. Results Among the randomised patients 54%(106) were post-menopausal, 71%(140) underwent breast conserving surgery(BCS) and 29%(56) mastectomy. At presentation, 12% (23) had T3, 63% (124) had T2, and 23% (46) had T1 tumors. Grade 3 tumors accounted for 70% (138) of cases. Among the patients, 60% (117) were HER2 positive, 31% (61) were triple negative, and 9% (18) were HER2 negative (ER or PgR positive). Anthracycline and taxane-based NACT were administered to 57% (106), while 38% (71) received a platinum-containing regimen. During SNB/TAD, a median of 4 nodes (interquartile range, 3-5) were removed. Among 184 patients with node marking data, 74% (136) had the involved node marked. The marked node was successfully removed in 94% (128) of these patients. Clip/coil only, Magseed and black dye were the commonest techniques used for node marking. The marked node was the sentinel node in 83% (106) of cases. Among 185 randomized patients with post-NACT response data, 68% (125) achieved a complete pathological response (pCR) in the breast, while 8% (15) had DCIS only and 22% (41) had invasive cancer. Among 105 patients with complete breast tumor response on imaging, 15% (16) had residual DCIS or invasive cancer. In the subset of patients with partial response or stable breast tumors on imaging (69 patients), 46% (32) had no residual tumor on histology (ypT0). Furthermore, 14% (26) exhibited partial or stable disease in the axilla on imaging but achieved complete pathological response on histology. Conclusions HER2-positive and triple-negative breast cancer cases predominate among patients undergoing NACT in the UK. Although 68% achieved a complete pCR (ypT0) in the breast, rates of BCS remain low. Notably, around 75% of randomized patients underwent node marking, with an intra-operative identification rate of 94%, demonstrating the successful implementation of node marking in the UK through the ATNEC trial. Citation Format: Amit Goyal, Andrea Marshall, Sophie Nicholls, Natalie Hammonds, Beatrix Elsberger, Duncan Wheatley, Janice Rose, Helen-Teresa Edwards, Abeer Shaaban, Roeum Butt, Gareth Jackson, Tara Homer, Luke Vale, Samreen Ahmed, Shama Puri, Sophie Gasson, Julie Bruce, Helen Higgins, Janet Dunn. Practice patterns and outcomes in the ongoing neoadjuvant ATNEC trial: node marking, response to NACT and breast conservation rates [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-23-05.

Abstract PO3-22-07: Predicting Additional Axillary Metastases in Breast Cancer Patients with Positive Targeted Axillary Dissection Lymph Nodes after Neoadjuvant Treatment

Abstract Background: Neoadjuvant chemotherapy (NACT) is increasingly used for axillary downstaging in clinically node-positive breast cancer patients, and a considerable proportion achieves axillary pathological complete response (ax-pCR). After NACT, axillary staging can be done by targeted axillary dissection (TAD). In case of metastases at TAD, axillary lymph node dissection (ALND) is offered regardless of metastases size. This contrasts primary surgery, where small sentinel node metastases (ypN0(i) and ypN1mi) and ≤2 positive sentinel nodes do not confer ALND, although a proportion of patients with small metastases have additional metastatic lymph nodes (LNs) in the axilla. So far, the residual metastatic burden in the axilla when TAD LNs are positive after NACT is unknown. If subgroups of patients with low residual metastatic burden in the axilla (non-TAD LNs) could be identified, these subgroups may be offered de-escalated axillary treatment. Therefore, we investigated the risk of residual metastatic burden in the axilla when the TAD LNs harbored metastases. Methods: We retrospectively retrieved DBCG data on patients staged by TAD after NACT in Denmark between 1.1.2016-31.8.2021. We registered: age, breast biopsy date, type of surgery, type of axillary surgery, count of LNs, sentinel nodes, and marked lymph nodes with and without metastases, including metastasis size, breast tumor histology and receptor subtype, breast tumor size at diagnosis and in the surgical specimen, malignancy grade and type of neoadjuvant treatment. We excluded patients with inflammatory breast cancer, &amp;lt; 4/&amp;gt;8 cycles of NACT, or a non-standard NACT regimen. The primary outcome was risk factors for having high ( &amp;gt;3), low (1-3), or no residual metastatic burden in the axilla when the TAD LNs harbored metastases. We modeled risk factors for both high and low residual metastatic burden in the axilla using multivariable logistic regression and constructed risk models based on the regression coefficients. Results: We identified 1626 patients receiving NACT and TAD in the inclusion period. After excluding ineligible patients and patients who achieved ax-pCR with no subsequent ALND (46%), the study included 383 patients with positive LNs at TAD for further analysis: thereof 188, 127, and 68 with 0, 1-3 and &amp;gt;3 positive non-TAD LNs, respectively. In the adjusted logistic regression analysis, we found that breast pCR (OR= 0.06, 95% CI &amp;lt; .01-0.41, p &amp;lt; .001) and a low proportion of positive TAD LNs (0-66% vs &amp;gt;66%) (OR=0.32, 95% CI 0.17-0.58, p = &amp;lt; .001) were associated with low risk of high residual metastatic burden in the axilla. Patients with one or both low-risk factors present had an 8% (14 of 176 patients) risk of high residual metastatic burden in the axilla. The predictive value of the model for having &amp;lt; 3 non-TAD LN metastases was 92%. When analyzing the 315 patients with ≤3 positive non-TAD LNs, the adjusted logistic regression analysis of 1-3 vs 0 positive non-TAD LNs showed that ypN0(i) in the TAD LN (OR=0.14, 95% CI 0.04-0.53, p = 0.002), small tumor size at diagnosis (20-49 mm vs ≥ 50 mm) (OR = 0.29, 95% CI 0.14-0.60, p = 0.002), breast pCR (OR= 0.38, 95% CI 0.15-0.98, p = 0.04) and low proportion of positive TAD LNs (33-66% vs &amp;gt;66%) (OR= 0.46, 95% CI 0.27-0.77, p = 0.01) were associated with no residual metastases in the axilla. Using these risk factors, 19% (11/58) of the patients in the lowest risk quartile had further metastatic spread to the axilla. Conclusion: Based on an extensive breast cancer registry, we find that breast pCR, low proportion of positive TAD LNs, small metastases, and small tumor size are associated with low risk of residual metastatic LNs in the axilla when the TAD LNs are positive after NACT. With these risk factors, we propose two models to identify patients with low non-TAD residual metastatic burden and patients with a high likelihood of no further metastases. The models can guide breast surgeons in de-escalating axillary treatment in these groups. Citation Format: Frederikke Munck, Maj-Britt Jensen, Ilse Vejborg, Maria Gerlach, Maja Maraldo, Niels Kroman, Tove Tvedskov. Predicting Additional Axillary Metastases in Breast Cancer Patients with Positive Targeted Axillary Dissection Lymph Nodes after Neoadjuvant Treatment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-22-07.

Abstract PO5-23-01: SentiNeo: A feasibility study on a magnetic approach to targeted axillary dissection and sentinel lymph node biopsy after neoadjuvant chemotherapy

Abstract Background Neoadjuvant chemotherapy (NAC) is increasingly used to treat certain breast cancer subtypes, and often, with good axillary response. Axillary management after NAC has become a contentious topic. Low detection rates and high false negative rates for sentinel lymph node biopsies (SLNB) could be due to the chemotherapy-induced fibrosis and blockage of the lymphatic drainage. Complete axillary response raises the dilemma of whether axillary clearance is still necessary after NAC in node positive patients. Targeted axillary dissection (TAD) is a safe alternative but the optimal method for index metastatic lymph node marking and lymphatic mapping of additional SLNs is largely undetermined. In SentiNeo, we study the feasibility and accuracy of using superparamagnetic iron oxides nanoparticles (SPIO) and magnetic seeds for axillary staging after NAC. Methods: Patients from two hospitals undergoing NAC were included: 40 without (cN0) and 40 with (cN+) axillary metastases. For cN0, SPIO was injected before and Technetium (Tc99) after NAC. For cN+, a magnetic clip was inserted into the index metastatic node together with SPIO injection before and Tc99 after NAC. Endpoints were 1) Index node detection and 2) SLN detection and concordance rates. Detection rate was defined as the proportion of patients who had SLNs detected as per tracer (using both magnetometer and gamma probe). Concordance was defined as the number of nodes marked by both SPIO and Tc99, divided by the total number of Tc99 marked nodes. As this is a feasibility study, no calculations for statistical significance were done. Results: All 80 patients have been included and 60 have completed NAC and surgery: 35 cN0 with SLNB and 25 cN+ with TAD. Overall, SLN detection rates (excluding the index nodes) were 83.3% (50/60) for SPIO and 76.7% (46/60) for Tc99. In cN0, SLN detection rate was 85.7% (30/35) for SPIO) and 88.6% (31/35) for Tc99. In cN+, the index node was found in 24 of 25 patients. One patient did not receive a magnetic clip due to administrative error. The SLN detection rate (excluding index nodes) was 80% (20/25) for SPIO) and 60% (15/25) for Tc99. In total, 142 lymph nodes were retrieved, of which 71 contained both tracers. The concordance was 84% (out of 84 nodes detected with Tc99, 71 were also detected with SPIO). However, the reversed concordance was only 55% (out of 129 nodes detected with SPIO, 71 were radioactive). The overall mean (median) number of retrieved nodes were 2.2 (2) for SPIO and 1.4 (1) for Tc99. Conclusions: In this pilot study we have shown that injecting SPIO before NAC is feasible with detection rates comparable to Tc99injected after NAC. More nodes were retrieved with SPIO and furthermore, we hypothesize that these nodes might be more representative than nodes detected with a tracer injected after NAC. Finding the index node using the SentiMag probe was easy. For SLN detection with SPIO the same probe was used, making the magnetic approach to axillary staging an appealing alternative with no need for an extra localisation before surgery or access to nuclear medicine facilities. These findings justify a larger study which is in planning. Table. Citation Format: Kian Chin, Roger Olofsson Bagge, Nushin Mirzaei, Anikó Kovács, Henrik Leonhardt, Pontus Zaar, Andreas Karakatsanis, Eirini Pantiora, Staffan Eriksson, Maria Ekholm, Alastair Thompson, Peter Barry, Michael Boland, Vivian Man, Ava Kwong, Fredrik Wärnberg. SentiNeo: A feasibility study on a magnetic approach to targeted axillary dissection and sentinel lymph node biopsy after neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-23-01.

Evaluating Radar Reflector Localisation in Targeted Axillary Dissection in Patients Undergoing Neoadjuvant Systemic Therapy for Node-Positive Early Breast Cancer: A Systematic Review and Pooled Analysis.

SAVI SCOUT® or radar reflector localisation (RRL) has proven accurate in localising non-palpable breast and axillary lesions, with minimal interference with MRI. Targeted axillary dissection (TAD), combining marked lymph node biopsy (MLNB) and sentinel lymph node biopsy (SLNB), is becoming a standard post-neoadjuvant systemic therapy (NST) for node-positive early breast cancer. Compared to SLNB alone, TAD reduces the false negative rate (FNR) to below 6%, enabling safer axillary surgery de-escalation. This systematic review evaluates RRL's performance during TAD, assessing localisation and retrieval rates, the concordance between MLNB and SLNB, and the pathological complete response (pCR) in clinically node-positive patients post-NST. Four studies (252 TAD procedures) met the inclusion criteria, with a 99.6% (95% confidence [CI]: 98.9-100) successful localisation rate, 100% retrieval rate, and 81% (95% CI: 76-86) concordance rate between SLNB and MLNB. The average duration from RRL deployment to surgery was 52 days (range:1-202). pCR was observed in 42% (95% CI: 36-48) of cases, with no significant migration or complications reported. Omitting MLNB or SLNB would have under-staged the axilla in 9.7% or 3.4% (p = 0.03) of cases, respectively, underscoring the importance of incorporating MLNB in axillary staging post-NST in initially node-positive patients in line with the updated National Comprehensive Cancer Network (NCCN) guidelines. These findings underscore the excellent efficacy of RRL in TAD for NST-treated patients with positive nodes, aiding in accurate axillary pCR identification and the safe omission of axillary dissection in strong responders.

Implementation of the Targeted Axillary Dissection Procedure in Clinically Node-Positive Breast Cancer: A Retrospective Analysis.

The targeted axillary dissection (TAD) procedure is used in clinically positive lymph node (cN+) breast cancer to assess whether pathological complete response (pCR) is achieved after neoadjuvant systemic therapy (NST) to decide on de-escalation of axillary lymph node dissection (ALND). In this study, we review the implementation of the TAD procedure in a large regional breast cancer center. All TAD procedures between 2016 and 2022 were reviewed. The TAD procedure consists of marking pre-NST the largest suspected metastatic lymph node(s) using a radioactive I-125 seed. During surgery, the marked node was excised together with a sentinel node procedure. Axillary therapy (ALND, axillary radiotherapy, or nothing) recommendations were based on the amount of suspected positive axillary lymph nodes (ALNs < 4 or ≥ 4) pre-NST and if pCR was achieved after NST. A total of 312 TAD procedures were successfully performed in 309 patients. In 134 (43%) cases, pCR of the TAD lymph nodes were achieved. Per treatment protocol, 43 cases (14%) did not receive any axillary treatment, 218 cases (70%) received adjuvant axillary radiotherapy, and 51 cases (16%) underwent an ALND. During a median follow-up of 2.8 years, 46 patients (14%) developed recurrence, of which 11 patients (3.5%) had axillary recurrence. Introduction of the TAD procedure has resulted in a reduction of 84% of previously indicated ALNDs. Moreover, 18% of cases did not receive adjuvant axillary radiotherapy. These data show that implementation of de-escalation axillary treatment with the TAD procedure appeared to be successful.

Quantum-walk search in motion.

In quantum computing, the quantum walk search algorithm is designed for locating fixed marked nodes within a graph. However, when multiple marked nodes exist, the conventional search algorithm lacks the capacity to simultaneously amplify the marked nodes as well as identify the correct chronological ordering between the marked nodes, if any. To address this limitation, we explore a potential extension of the algorithm by introducing additional quantum states to label the marked nodes. The labels resolve the ambiguity of simultaneous amplification of the marked nodes. Additionally, by associating the label states with a chronological ordering, we can extend the algorithm to track a moving particle on a two-dimensional surface. Our algorithm efficiently searches for the trajectory of the particle and is supported by a proposed quantum circuit. This concept holds promise for a range of applications, from real-time object tracking to network management and routing.

On the quantum simulation of complex networks

Quantum walks provide a natural framework to approach graph problems with quantum computers, exhibiting speedups over their classical counterparts for tasks such as the search for marked nodes or the prediction of missing links. Continuous-time quantum walk algorithms assume that we can simulate the dynamics of quantum systems where the Hamiltonian is given by the adjacency matrix of the graph. It is known that such can be simulated efficiently if the underlying graph is row-sparse and efficiently row-computable. While this is sufficient for many applications, it limits the applicability for this class of algorithms to study real world complex networks, which, among other properties, are characterized by the existence of a few densely connected nodes, called hubs. In other words, complex networks are typically not row-sparse, even though the average connectivity over all nodes can be very small. In this work, we extend the state-of-the-art results on quantum simulation to graphs that contain a small number of hubs, but that are otherwise sparse. Hopefully, our results may lead to new applications of quantum computing to network science.

Abstract P3050: Cpne5 Is Necessary For Normal Murine Sinoatrial Node Function In Vivo

Cpne5 ( Copine 5 ) is a Ca 2+ -dependent phospholipid binding protein implicated in membrane trafficking but has no known role within the heart to date. In single-cell RNA-sequencing of the developing mouse heart, we previously found Cpne5 gene expression to be highly enriched in the cardiac conduction system (CCS). Further, variants in CPNE5 were identified in 6 independent GWAS related to heart rate variability in humans. We therefore hypothesized that Cpne5 is necessary for normal CCS function through Ca 2+ -dependent membrane trafficking of ion channels. Whole mount immunostaining with 3D volumetric imaging (iDISCO+) of intact WT hearts demonstrated robust and specific protein expression of Cpne5 throughout all CCS components, including the sinoatrial node (SAN) and SAN-transitional cells. Next, to assess the necessity of Cpne5 within the CCS, systemic knockout mice (Cpne5KO) were generated using CRISPR/Cas9. Successful deletion of Cpne5 in CRISPR-generated KO mice was confirmed by PCR and, at the protein level, immunofluorescence. Homozygous Cpne5KO mice were viable, showed normal growth and allele frequencies segregated in a normal Mendelian fashion. No gross anatomic defects of the CCS were observed in Cpne5KO mice and transthoracic echocardiogram studies showed a slight reduction in left ventricular fractional shortening but otherwise a structurally normal heart. Notably, while surface electrocardiogram (ECG) demonstrated normal intervals (PR, QRS, QTc), Cpne5KO mice exhibited pronounced sinus arrhythmia, with notable sinus pauses, sinus bradycardia, and increased heart rate variability as compared to WT littermate controls on long term telemetry. Systemic loss-of-function of Cpne5 in mice resulted in marked sinus node dysfunction, consistent with human GWAS data, implicating a novel role for Cpne5 in CCS function and/or development. Additional phenotyping and molecular studies, including CPNE5 deletion in human induced-pluripotent cell-derived SAN-like cells, are ongoing to further elucidate its underlying mechanism.

Virtual reality-based training and pre-operative planning for head and neck sentinel lymph node biopsy

ObjectiveSentinel lymph node biopsy (SLNB) is crucial for managing head and neck skin cancer. However, variable lymphatic drainage can complicate SLN detection when using Single-Photon Emission Computed Tomography (SPECT) or lymphoscintigraphy. Virtual Reality (VR) can contribute to pre-operative planning by simulating a realistic 3D model, which improves orientation. VR can also facilitate real-patient training outside the operating room. This study explored using a VR platform for pre-operative planning in head and neck skin cancer patients undergoing SLNBs and assessed its value for residential training. Materials and methodsIn this prospective technology pilot study, attending surgeons and residents who performed 21 SLNB operations on patients with head and neck skin cancers (81% males, mean age 69.2 ± 11.3) used a VR simulation model based on each patient's pre-operative SPECT scan to examine patient-specific anatomy. After surgery, they completed a questionnaire on the efficiency of the VR simulation as a pre-operative planning tool and training device for residents. ResultsThe attending surgeons rated the VR model's accuracy at 8.3 ± 1.6 out of 10. Three-quarters (76%) of residents reported increased confidence after using VR. The physicians rated the platform's contribution to residents' training at 7.4 ± 2.1 to 8.9 ± 1.3 out of 10. ConclusionA VR SLNB simulation can accurately portray marked sentinel lymph nodes. It was rated high as a surgical planning and teaching tool among attending surgeons and residents alike and may play a role in pre-operative planning and resident training. Further studies are needed to explore its applications in practice.

Comparing Methods for Targeted Axillary Dissection in Breast Cancer Patients: A Nationwide, Retrospective Study.

Several techniques exist for performing targeted axillary dissection (TAD) after neoadjuvant chemotherapy with the removal of the sentinel node and a marked metastatic lymph node (LN). Two-step methods include coil-marking of the metastatic LN at diagnosis and re-marking with an intraoperatively identifiable marker before surgery. Because nondetection of the marked lymph node (MLN) warrants axillary clearance and many patients achieve axillary pathological complete response (ax-pCR), the success of TAD is crucial. We compare various two-step TAD methods in a Danish national cohort. We included patients who received two-step TAD between January 1, 2016 and August 31, 2021. Patients were identified from the Danish Breast Cancer Group database and cross-checked with locally accessible lists. Data were extracted from the patient's medical files. We included 543 patients. In 79.4%, preoperative, ultrasound-guided re-marking was possible. Nonidentification of the coil-marked LN was more likely in patients with ax-pCR. The second markers used were hook-wire, iodine seeds, or ink marking on the axillary skin. Of patients with successful secondary marking, the MLN identification rate (IR) was 91%, and the sentinel node (SN) IR was 95%. Marking with iodine seeds was significantly more successful than ink marking with an odds ratio of 5.34 (95% confidence interval 1.62-17.60). The success rate of the complete TAD with the removal of MLN and SN was 82.3%. With two-step TAD, nonidentification of the coiled LN before surgery is frequent, especially in patients with ax-pCR. Despite successful remarking, the IR of the MLN at surgery is inferior to one-step TAD.

Practice patterns in ongoing neoadjuvant ATNEC trial for patients with cT1-3N1M0 breast cancer: Response to neoadjuvant chemotherapy (NACT), targeted axillary dissection and breast conservation rates.

e12609 Background: Patients presenting with cT1-3N1M0 breast cancer often receive NACT to enable breast and/or axillary conservation. Targeted axillary dissection (TAD) (sentinel node biopsy (SNB) + removal of marked involved node) has been proposed to reduce the false negative rate of SNB after NACT in cN1 patients. In ATNEC, cT1-3N1M0 patients receive NACT followed by SNB/TAD. If the sentinel nodes (SN) have converted to benign (ypN0), patients are randomly assigned to Axillary Treatment vs no Axillary Treatment. Node marking is recommended in the study and sites are offered training to help them adopt node marking in a standardized way. Objectives: To prospectively evaluate the practice patterns and response to NACT, uptake of node marking, marked node identification rates and breast conservation rates in the ongoing UK ATNEC trial. The trial aims to recruit 1900 patients. Methods: Data for all patients who were randomized until 01-Feb-23 across 78 UK centers were included in these analyses. Patients were cT1-3N1M0 at presentation, received NACT and were found to have no residual nodal disease (ypN0) on SNB/TAD. Results: Among the 120 randomized patients (median age 54 [range 28-77] years) (median BMI 26.4 [range 17.6-51.1]), 53% (64) were post-menopausal, 78% (94) had breast conserving surgery (BCS) and 22% (26) mastectomy. At presentation, 14% (17) were T3, 64% (77) T2 and 20% (24) T1. 70% (84) had grade 3 tumors. 62% (74) were HER2 positive, 31% (37) triple negative (TNBC) and 9% (7) HER2 negative (ER or PgR positive). 54% (65) had an anthracycline and taxane based NACT and 36%(43) had platinum containing NACT. Median of 4 nodes [interquartile range 3-5] were removed during SNB/TAD. Of 109 patients with node marking data, the involved node was marked in 73% (80). The marked node was identified and removed in 95% (76/80), marked node was the SN in 88% (67/76). Of the 109 patients with data for breast tumor post NACT, 69% (75) had pathological complete response (pCR), 7% (8) DCIS only, 24% (26) invasive cancer. Of the 63 patients with complete breast tumor response on imaging, 17% (11) had residual DCIS/invasive cancer. 50% (21/42) of patients with partial response or stable breast tumor on imaging had no residual tumor on histology (ypT0). Of the 107 patients with data on post NACT axillary imaging, 14% (15) had partial or stable disease but pCR on histology. Conclusions: Majority of UK patients having NACT have HER2 positive or TNBC. Although 69% patients had a pCR (ypT0) in the breast, BCS rates remain low. Imaging has limited accuracy in predicting pCR after NACT. 3 in 4 patients randomized had their node marked, with a 95% intra-operative identification rate; demonstrating ATNEC has successfully rolled out node marking in the UK. Clinical trial information: NCT04109079 .

Tailored axillary surgery (TAS) in patients with clinically node-positive breast cancer in the upfront surgery setting: A prospective, single-arm, multicenter trial.

TPS628 Background: Axillary lymph node dissection (ALND), which can induce lymphedema, has been omitted in clinically node-negative(cN0) patients with positive sentinel lymph nodes (SLNs) if they meet the eligibility criteria of ACOSOG Z0011. Furthermore, the omission of ALND has been attempted through targeted axillary dissection (TAD) in patients whose cN+ status converts to ycN0 after neoadjuvant chemotherapy. However, ALND remains the standard of care in patients with cN+ who undergo upfront surgery. The aims of this trial are to establish a surgical method of tailored axillary surgery (TAS), which combines TAD and SLN biopsy among patients with cN+ who undergo upfront surgery, and to determine the appropriate criteria for a Phase III TAS trial. Methods: We have planned a single-arm Phase II trial to confirm the feasibility and assess patient eligibility for TAS. A total of 300 patients will be enrolled from 33 study sites in Japan. The eligibility criteria are as follows: 1) histologically-proven invasive breast cancer, 2) upfront surgery is planned, 3) pathologically-diagnosed metastatic lymph node (cytology or core needle biopsy), 4) 1-3 LN metastases in level I by imaging, 5) cT1-3, and 6) females aged ≥18 and ≤74 years on the enrollment date. TAS involves removing marking lymph nodes by TAD (clip, wire, or tattoo) and SLNB, and ALND up to Level II are performed after TAS. These LNs are defined as non-TAS LNs. The primary endpoint is the non-TAS LNs positive rate. Clinicopathological factors (the number of suspected metastases by imaging, the number of metastases in LNs resected by TAS, tumor size, and invasive ductal/lobular carcinoma) are analyzed to predict the non-TAS LN metastasis rate (e.g., &lt; 10%). By using these clinicopathological factors, we determine the eligibility of TAS to omit ALND safely. The secondary endpoints are TAS LNs identification rate, labeled LNs identification rate, marked lymph node resection rate, arm edema incidence rate, and QOL (FACT-B, QuickDASH). After this feasibility study, we will conduct a phase III trial that omits ALND using TAS to investigate the regional recurrence rate.

Targeted Axillary Dissection with 125I Seed Placement Before Neoadjuvant Chemotherapy in a Danish Multicenter Cohort

BackgroundTargeted axillary dissection (TAD), with marking of the metastatic lymph node before neoadjuvant chemotherapy (NACT), is increasingly used for breast cancer axillary staging. In the case of axillary pathological complete response (ax-pCR), axillary lymph node clearance can be omitted. Several marking methods exist, most using re-marking before surgery. Feasibility, learning curve, and identification rate (IR) vary. Marking with 125I seed before NACT makes re-marking at surgery redundant, possibly increasing feasibility and IR. Here, TAD with 125I seed placed before NACT is evaluated in a Danish multicenter cohort.MethodsPatients staged with 125I TAD in Denmark between 1 January 2016 and 31 August 2021 were included. Patients were identified in radioactivity-emitting implant registries at the radiology departments and from the Danish Breast Cancer Group database. Data were extracted from patients’ medical records. Information on patient/tumor characteristics, 125I seed activity, marking period, TAD success, number of sentinel nodes (SNs), the histopathological status of excised nodes, and whether the marked lymph node (MLN) was an SN were registered.Results142 patients were included. The IR of the MLN was 99.3%, and the IR of the SLNB was 91.5%. TAD success was 91.5%. Minor challenges in marking or removal of the MLN were noted in three patients. In 72.3% of the patients, the MLN was a sentinel node. Overall, 40.8% had axillary pCR.ConclusionTAD with 125I seed marking before NACT is feasible without re-marking at surgery and with only minor surgical challenges. The IR is high. Staging with TAD spares 41% of breast cancer patients an axillary dissection.