Indocyanine Green Enhancement for Targeted Lymph Node Dissection in Axillary Staging

Multidisciplinary considerations in the treatment of triple-negative breast cancer.

Introduction: NCCN guidelines support safe omission of axillary lymph node dissection (ALND) in clinically node negative (cN0) patients with 1-2 positive sentinel lymph nodes (SLNs) if they meet the eligibility criteria of ACOSOG Z0011 and AMAROS trials. For patients undergoing neoadjuvant systemic anti-cancer therapy (SACT), targeted axillary dissection (TAD) is recognised as a highly accurate technique to spare patients ALND whose cN+ status converts to ypN0. However, there is no consensus on the optimal management of patients with low volume cN+ disease undergoing upfront surgery with ASCO guidelines recommending ALND and NCCN guidelines supporting primary TAD. In this context, ‘primary TAD’ combines these principles to de-escalate axillary surgery in patients with ultrasound-detected abnormal or biopsy-proven 1-2 positive lymph nodes (cN1) that are clipped for removal in combination with SLN biopsy to optimise further axillary surgical decisions. This method evolved after biopsy-proven involved nodes were missed during planned ALND. Aims: To evaluate the early outcomes of primary TAD in a single high volume tertiary cancer unit in the United Kingdom (UK). Methods: A prospective database of the first 126 patients ≥ 18 years with cT1-2cN1 undergoing primary breast surgery either as breast conserving surgery or mastectomy with primary TAD between 30/08/2018 and 12/03/2024 at the Royal Marsden NHS Foundation Trust was evaluated. We define primary TAD as removal of 1-2 marked axillary nodes using Magseed, either biopsy-proven or suspicious on axillary ultrasound scan but indeterminate biopsy, combined with SLN mapping with the use of Tc99m / SPIO / Patent Blue V. The clipped node(s) were sent to histopathology (as already known to contain disease), and additional SLNs underwent intra-operative assessment using one step nucleic acid (OSNA). If a total of 3 positive nodes (including marked nodes + those with macrometastasis on OSNA) were confirmed, the patient underwent completion ALND in the same operative sitting. If only 1-2 nodes, total from marked nodes and OSNA, contained macrometastatic disease, the patient was spared ALND and offered regional nodal irradiation (RNI). Patient demographics, tumor characteristics, treatment details and outcomes including breast and/or axillary recurrence, distant recurrence and overall survival were assessed. Descriptive statistics were used to report results. Results: A total of 125 women and 1 man underwent primary TAD. The median age at surgery was 60.5 years. The majority of tumors (109/126) were hormone positive (HR+) and HER2 negative (86.5%), with 78/126 of the luminal A subtype (61.9%) and cT2 with a median tumor size of 24mm (IQR 17-34.8). Pre-operatively, 24/126 (19%) had suspicious nodes unproven on biopsy, 1 abnormal and proven axillary metastatic node was detected in 74/126 (58.7%), and 2 abnormal with 1 biopsy-proven node in 28/126 (22.3%). Clipped node(s) were successfully removed in 125 patients. A median of 3 non-Magseed SLNs were excised for OSNA, of which median 0 (IQR 0-1) were positive. Of 126 patients, 121 (96%) had axillary metastatic Magseed node(s), 97 (77%) avoided ALND, 27 (21.4%) underwent immediate ALND, 2 (1.6%) underwent delayed ALND post SACT. Out of 126, 65 (51.6%) patients underwent RNI. Median follow-up was 21.2 months (IQR 11.2- 35.8); 1 patient developed axillary recurrence requiring further axillary surgery, no patients developed breast recurrence, and 3 patients developed and died of distant metastasis. Conclusion: Primary TAD is feasible with reassuring early oncological outcomes but long-term follow-up is required. This method can be utilised to optimise axillary surgery in suitable patients to safely facilitate omission of routine ALND. Citation Format: Radhika A Merh, Jennifer Rusby, Marios Konstantinos Tasoulis, Katherine Krupa, Rachel O'Connell, Gerald Gui, William Allum, Victoria Sinnett, Julie Scudder, Peter Barry. Avoidance of axillary lymph node dissection in patients with 1-2 pre-operative positive lymph nodes undergoing upfront surgery: ‘Primary targeted axillary dissection’ early outcomes [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-07-11.

Introduction Sentinel lymph node (SLN) staging is currently used to avoid complete axillary lymph node dissection (ALND) in breast cancer (BC) patients with negative SLNs without jeopardizing survival or regional control. International guidelines keep recommending ALND in the presence of positive (+) SLNs. However SLN is the only site of axillary metastasis (MTS) in many cases (60%). Retrospective studies have also shown a low risk of locoregional relapse in patients with SLNs+ not receiving ALND.This latter finding was recently confirmed in a randomized trial comparing SLN biopsy (SLNB) alone with SLNB followed by ALND in patients with 1-2 SLNs+. However the observation of both similar relapse rate and survival in the 2 arms and the conclusion of a non-inferiority of SLNB compared to ALND require cautiousness because of some study limitations: premature enrollment cessation due to death rate lower than expected, short follow-up (6 years), small tumor size (≤2cm in 70% of cases), frequent presence of only microMTS in SLN (40%), prevalent use of “whole breast” adjuvant radiotherapy (>90%) which irradiates the breast but also the I° axillary level, thereby contributing to the low rate of regional relapse in the SLNB arm due to lymph node sterilization. Consequently further randomized trials with more precise selection criteria based on homogeneous clinico-pathological features and with longer follow-up are needed to confirm that performing only SLNB does not affect survival or relapse risk in patients with 1-2 SLNs+. Materials and Methods Primary and secondary aims of the present 2-arm randomized trial are to assess whether ALND omission in BC patients with 1-2 SLNs+ is associated with worse survival and/or increased rate of regional/distant relapse, respectively, thus evaluating whether SLNB is or is not inferior to ALND. Patients receive either conservative surgery or mastectomy and radiotherapy. They all undergo intraoperative SLNB and SLN evaluation, and are randomly assigned to either further dissection of level I-II axillary lymph nodes (standard ALND arm) or absence of any axillary surgery (experimental SLNB arm). According to International Guidelines post-surgery treatments. Eligibility criteria are: age 40-75 years; primary invasive T1-T2 tumor; axillary nodes clinically N0; no more than 2 SLNs presenting macroMTS at intraoperative or definitive histological evaluation; no distant MTS; no neoadjuvant therapy; no previous invasive BC, signed informed consent. Exclusion criteria are: in situ, inflammatory, contralateral BC; presence of only microMTS in the SLN+; pregnancy or breast feeding; comorbidity impeding adjuvant therapy. Follow-up controls foresee: clinical examination every 6 months for 5 years and yearly thereafter; annual mammography and breast echography; annual axillary echography for patients in the SLNB arm; additional laboratory and instrumental surveys in case of suspected onset of distant MTS. The primary endpoint is overall survival (OS). Secondary endpoints are disease-free survival (DFS) referring to distant MTS and to locoregional (ipsilateral breast or axillary, internal mammary or sopraclaveolar lymph nodes) disease recurrence. All analyses are performed both on all patients according to the Intention-To-Treat principle and excluding those patients who did not receive the axillary treatment randomly assigned. Citation Format: Corrado Tinterri, Emilia Marrazzo, Federico Frusone, Wolfgang Gatzemeier, Erika Barbieri, Andrea Sagona, Alberto Bottini, Valentina Errico, Alberto Testori, Giuseppe Canavese. Preservation of axillary lymph nodes compared to complete dissection in T1-T2 breast cancer patients presenting 1-2 metastatic sentinel lymph nodes: A multicenter randomized clinical trial. Sinodar One Study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT3-01-02.

Prospective trials have demonstrated sentinel lymph node (SLN) false-negative rates of less than 10% when 3 or more SLNs are retrieved in patients with clinically node-positive breast cancer rendered clinically node-negative with neoadjuvant chemotherapy (NAC). However, rates of nodal recurrence in such patients treated with SLN biopsy (SLNB) alone are unknown because axillary lymph node dissection (ALND) was performed in all patients, limiting adoption of this approach. To evaluate nodal recurrence rates in a consecutive cohort of patients with clinically node-positive (cN1) breast cancer receiving NAC, followed by a negative SLNB using a standardized technique, and no further axillary surgery. From November 2013 to February 2019, a cohort of consecutively identified patients with cT1 to cT3 biopsy-proven N1 breast cancer rendered cN0 by NAC underwent SLNB with dual tracer mapping and omission of ALND if 3 or more SLNs were identified and all were pathologically negative. Metastatic nodes were not routinely clipped, and localization of clipped nodes was not performed. The study was performed in a single tertiary cancer center. Omission of ALND in patients with cN1 breast cancer after NAC if 3 or more SLNs were pathologically negative. The primary outcome was the rate of nodal recurrence among patients with cN1 breast cancer treated with SLNB alone after NAC. Of 610 patients with cN1 breast cancer treated with NAC, 555 (91%) converted to cN0 and underwent SLNB; 234 (42%) had 3 or more negative SLNs and had SLNB alone. The median (IQR) age of these 234 patients was 49 (40-58) years; median tumor size was 3 cm; 144 (62%) were ERBB2 (formerly HER2)-positive, and 43 (18%) were triple negative. Most (212 [91%]) received doxorubicin-based NAC; 205 (88%) received adjuvant radiotherapy (RT), and 164 (70%) also received nodal RT. At a median follow-up of 40 months, there was 1 axillary nodal recurrence synchronous with local recurrence in a patient who refused RT. Among patients who received RT (n = 205), there were no nodal recurrences. This cohort study found that in patients with cN1 disease rendered cN0 with NAC, with 3 or more negative SLNs with SLNB alone, nodal recurrence rates were low, without routine nodal clipping. These findings potentially support omitting ALND in such patients.

Introduction: Axillary lymph node dissection (ALND) has always been part of breast cancer (BC) treatment. However, during the past 25 years, the surgical management of the axilla has shifted towards a more conservative approach. Until now, ALND has remained the standard surgical technique when the sentinel lymph node (SLN) is macrometastatic. However, ALND may now be considered overtreatment for early-stage BC. The SINODAR-ONE trial is a prospective non-inferiority multicenter randomized study aimed at assessing the role of ALND in patients undergoing either breast-conserving surgery (BCS) or mastectomy for T1-2 BC presenting 1-2 macrometastatic SLNs. Objectives: The primary endpoint was to evaluate whether sentinel lymph node biopsy (SLNB) only was associated with clinically relevant worsening of the prognosis compared with ALND in terms of overall survival (OS). The secondary endpoint was to evaluate whether there was increased regional (lymph node recurrence) or distant recurrence in terms of recurrence-free survival (RFS) in patients with macrometastatic SLN who did not undergo ALND. Methods: Patients were randomly assigned (1:1 ratio) to either removal of ≥10 axillary level I/II non-SLNs followed by adjuvant therapy (standard arm) or no further axillary treatment (experimental arm). Results: The trial started in April 2015 and ceased in April 2020, involving 889 patients. The majority of the patients (75.2%) underwent BCS; 328 of 439 patients (74.7%) in the standard treatment arm, and 333 of 440 patients (75.7%) in the experimental treatment arm. 218 patients (24.8%) underwent mastectomy. SLN status at randomization was comparable between the two groups of treatment, with a median number of two SLNs removed and a median number of one positive SLN in both arms. The median number of non-SLNs identified at definitive histopathological evaluation was 16 (interquartile range [IQR] 12–21) in the ALND group. Overall, 193 of 439 patients (44.0%) in the standard treatment arm had additional macrometastases in the removed axillary lymph nodes. However, the median number of positive non SLNs was 0 (IQR 0–1) in the ALND group. Median follow-up was 34.0 months. There were eight deaths (ALND, 4; SNLB only, 4), with a 5-year cumulative mortality of 5.8% and 2.1% in the standard and experimental arm, respectively (p = 0.984). There were 26 recurrences (ALND 11; SNLB only, 15), with a 5-year cumulative incidence of recurrence of 6.9% and 3.3% in the standard and experimental arm, respectively (p = 0.444). Only one axillary lymph node recurrence was observed in each arm. The 5-year OS rates were 98.9% and 98.8%, in the ALND and SNLB only arm, respectively (p = 0.936). Conclusion: The 3-year survival and relapse rates of T1-2 BC patients with 1-2 macrometastatic SLNs treated with SLNB only, and adjuvant therapy, were not inferior to those of patients treated with ALND. These results do not support the use of routine ALND in patients undergoing BCS. However, given the low number of patients treated with mastectomy, there is no certainty that ALND omission can be extended also to this sub-group. In order to collect further evidence regarding the safety of the experimental treatment in patients candidates for mastectomy, the reopening of the enrollment of these patients as part of a single-arm experimental study started in June 2022. Citation Format: Damiano Gentile, Wolfgang Gatzemeier, Andrea Sagona, Erika Barbieri, Alberto Testori, Valentina Errico, Alberto Bottini, Simone Di Maria Grimaldi, Giulia Caraceni, Luca Boni, Paolo Bruzzi, Bethania Fernandes, Davide Franceschini, Ruggero Spoto, Rosalba Torrisi, Marta Scorsetti, Armando Santoro, Giuseppe Canavese, Corrado Tinterri. Preservation of axillary lymph nodes in breast cancer patients undergoing mastectomy with 1-2 metastatic sentinel lymph nodes: The current status and future perspectives of the multicenter randomized clinical trial SINODAR-ONE [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 OT1-06-01.

The surgical management of the axilla has undergone significant evolution during the past 20 years. The inception of the sentinel lymph node (SLN) concept and the clinical validation of lymphatic mapping and SLN biopsy (SLNB) starting in the 1990s, challenged the century-old primacy of axillary lymph node dissection (ALND) as the procedure of choice for staging the axilla and ushered us into a new era of axillary surgical management. Randomized clinical trials, evaluating SLNB with or without completion ALND in patients with operable breast cancer and negative SLN(s), established SLNB alone as the standard of care for staging the axilla in this setting. These trials established the performance characteristics of SLNB and factors that affect identification and false-negative rate and led to the refinement of the original SLN node concept. More importantly, the results from these trials provided the launching pad for the conduct of additional randomized trials evaluating SLNB alone vs. SLNB with completion ALND in patients with operable breast cancer and limited SLN involvement (micrometastases in IBCSG 23-01 or macrometastases in 1 or 2 SLNs in ACOSOG Z0011). These trials demonstrated no disease-free or overall survival advantage with completion ALND, thus expanding the use of SLNB alone in patients with limited SLN involvement. Another clinical trial (AMAROS) compared the effect of axillary radiotherapy vs. completion ALND in patients with positive SLN(s) and demonstrated equivalent oncologic outcomes between the two approaches but with less morbidity in favor of axillary radiotherapy. Thus, for patients who meet the criteria for inclusion in the ACOSOG Z11 and the IBCSG 23-01 trials, SLNB alone without completion ALND is adequate for staging the axilla. For patients who meet the criteria for inclusion in the AMAROS trial, axillary radiotherapy appears to represent a better option than completion ALND. Lastly, the increasing use of neoadjuvant chemotherapy in appropriately-selected patients with large operable breast cancer and the resulting axillary nodal down-staging in a considerable proportion of patients with axillary lymph node involvement at presentation, has led to an increased interest in the evaluation of SLNB in this setting. After a decade-old debate, the prevailing approach for patients who present with clinically negative axilla and are considered for neoadjuvant chemotherapy, is to perform SLNB after neoadjuvant chemotherapy. This approach has now also been expanded to include patients who present with clinically (or biopsy proven) involvement of the axillary nodes, become clinically node-negative after neoadjuvant chemotherapy and have negative SLNB. Several prospective trials (ACOSOG Z1071, SENTINA, SN FNAC) have recently demonstrated the feasibility and accuracy of SLNB alone in this setting. Provided that certain procedures are followed (removal of 3 or more SLNs, dual-agent lymphatic mapping, localization and removal of previously biopsied positive nodes and even the use of immunohistochemistry in the SLN evaluation), the false-negative rate of SLNB drops to below 10%. Adoption of this approach has the potential to further decrease the use of ALND in patients who present with documented axillary lymph node involvement. Citation Format: Mamounas EP. Optimal management of the axilla: A look at the evidence. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr CS1-2.

Background The probability of axillary lymph node converting from positive to negative after neoadjuvant systemic therapy (NST) for breast cancer patients is approximately 40%. A variety of axillary lymph node biopsy surgeries based on sentinel lymph node biopsy (SLNB) can help to omit axillary lymph node dissection (ALND). The common disadvantages, however, are mainly the restrictions, such as the need for strict regulation of the use of radiotracers, the high number of retrieved lymph nodes required, and the need to purchase ancillary equipment. The more restrictions there are, the more they limit the spread and availability of the technique and, more importantly, reduce the number of patients who will benefit. In fact, for patients with metastatic lymph nodes, the sentinel lymph nodes must be included in the lymph nodes that have metastasized. If these metastatic lymph nodes can be accurately marked and precisely retrieved after NST, it is possible to assess whether the axillary lymph nodes are converted from positive to negative without the need for SLNB. Materials and methods Breast cancer patients with pathologically confirmed axillary lymph node metastases who were receiving NST were recruited for this study. Before NST, carbon nanoparticles suspension injections were injected into the cortex of the pathologically confirmed metastatic lymph node to stain the region where the metastatic lymph node was located. The lymph nodes in the stained region were retrieved by stained region lymph node biopsy (SrLNB) during the axillary surgery, followed by ALND, without the use of SLNB. Finally, the identification rate and false-negative rate (FNR) of SrLNB were statistically analyzed according to pathology data. Results A total of 159 patients were successfully enrolled in this study between September 24, 2020 and December 2, 2022, with an axillary pCR rate of 40.9% (65/159). The identification rate of SrLNB was 100% (159/159), with an overall FNR of 5.3% (5/94). Subgroup analysis revealed that in the subgroups of 1, 2, 3 and ≥4 SrLN, the FNR was 0%, 0%, 0% and 8.9% (5/56), respectively, whereas in the cN1, cN2 and cN3 subgroups the FNR was 7.7% (3/39), 2.6% (1/38) and 5.9% (1/17), respectively. The FNR indexes were within the safety threshold of 10% in all subgroups. Conclusion SrLNB has a high identification rate and a low FNR and is useful for screening patients with positive to negative axillary lymph nodes for omitting ALND. srLNB requires only the use of an affordable and radiation-free carbon nanoparticles suspension injection for marking, making the whole technique simpler and easier to disseminate. The data from this study also suggest that SLNB may not be mandatory for axillary biopsy in patients with positive axillary lymph nodes undergoing NST. Table 1. General characteristics of enrolled patients. Table 2. Analysis of factors affecting axillary pCR rates. Table 3. Analysis for the FNR of SrLNB. Citation Format: Jue Wang, Rui Chen, Cuiying Li, Hailing Zha, Qiannan Zhu, Lifeng Huang, Xiaoming Zha. Clinical study of stained region lymph node biopsy (SrLNB) in axillary surgery after neoadjuvant systemic therapy in patients with axillary lymph node positive breast cancer [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 PO2-23-06.

Objective Comparing the influence of neoadjuvant chemotherapy on sentinel lymph node biopsy and axillary lymph nodal staging. Methods From June 2005 to June 2007 one hundred and sixty five breast cancer patients of stage Ⅰ,Ⅱa,Ⅱb and Ⅲ underwent sentinel lymph node biopsy(SLNB) using 99mTc combining methylene blue dye as tracer to help axillary lymph node dissection(AND) were retrospectively reviewed. Sixty five patients staged Ⅱb or Ⅲ were treated with three circles neoadjuvant chemotherapy prior to SLNB and AND , another one hundred patients staged ⅠorⅡa had SLNB and AND directly without neoadjuvant chemotherapy.Results Average 14.60 axillary lymph nodes were retrieved in patients had neoadjuvant chemotherapy and 14.74 lymph nodes in patients did not have neoadjuvant chemotherapy(P>0.05),a mean number of 1.46 sentinel lymph nodes in neoadjuvant chemotherapy group and 1.5 sentinel lymph nodes in non-neoadjuvant chemotherapy(P>0.05), sentinel lymph node identification rate 96.9% in neoadjuvant chemotherapy group and 97% in non-neoadjuvant chemotherapy(P>0.05), the false negative rate was 4.6% in neoadjuvant chemotherapy group and 4% in non-neoadjuvant chemotherapy group(P>0.05). Conclusions The mean number of lymph nodes,sentinel lymph nodes,SLN identification rate and false-negative rates after neoadjuvant chemotherapy are similar to those seen in patients without neoadjuvant chemotherapy.The SLNB can accurately predict lymph node status of axillary lymph node following neoadjuvant chemotherapy. Key words: Breast cancer; Sentinel lymph node; Neoadjuvant chemotherapy

Background: Neoadjuvant chemotherapy (NAC) for breast cancer (BC) facilitates minimally invasive surgical approaches for both the primary tumor and axillary lymph nodes (LNs). When NAC is effective, breast-conserving surgery may be feasible, and axillary lymph node dissection (ALND) may be avoided. However, ALND is still commonly performed in node-positive patients, even when post-NAC imaging shows no evidence of residual nodal metastases. Recently, tailored axillary surgery/dissection (TAS/TAD) has gained attention. TAS involves pre-NAC placement of a marker in biopsy-proven metastatic LNs, followed by targeted excision of the marked LN, sentinel LNs, and any palpable nodes after NAC. This less invasive strategy may provide sufficient local control if the false-negative rate (FNR) of axillary evaluation is kept below 10%. Virtual sonography (VS)—a fusion technique combining real-time ultrasound (US) with pre-acquired imaging such as CT or MRI—enables accurate localization of target lesions. Commercial US systems already integrate this technology, offering benefits including minimal invasiveness, repeatability, and cost-effectiveness. In this ongoing study, we apply VS to enhance TAS precision during surgery following NAC. Objective: To evaluate the clinical utility of VS in TAS for patients with axillary LN metastases undergoing NAC in a prospective, multicenter observational setting. Study Design: In TAS, a marker is inserted into the metastatic LN prior to NAC as a surgical guide. While US is standard for identifying the marker, detection rates vary. TAS is considered feasible when the marker identification/excision rate reaches ≥ 95%. To enhance detection accuracy, this study utilizes VS for marker localization. Approved by the Central Ethics Committee of Gifu University (Approval No. 2024-005), this study follows these procedures: 1) Histopathological confirmation of axillary LN metastasis prior to NAC. 2) US-guided placement of an UltraCor™ Twirl™ marker in the metastatic LN. 3) Acquisition of axillary US volume data and longitudinal marker tracking using VS at three key time points: before NAC, after the second cycle, and preoperatively. 4) Measurement of the time required for marker identification using fusion imaging at the final preoperative session. 5) US-guided injection of blue dye (0.1-0.2 mL) into/around the marker-identified LN based on fusion images. 6) TAS during BC surgery, followed by radiographic confirmation of marker retrieval in the excised specimen. Marker presence confirms TAS success. Backup ALND will be performed thereafter. Eligibility Criteria:- Inclusion: 1) Primary BC with histologically or cytologically confirmed axillary LN metastasis. 2) Clinical stage cT0-T4, cN1-N3, M0 (Stage IIA-IIIC). 3) Planned NAC ( ≥ 3 cycles). 4) Age ≥ 20 years. 5) ECOG performance status 0-2. 6) Written informed consent. -Exclusion: 1) Inability to insert a marker into/around the metastatic LN. 2) Contraindications to NAC for systemic or medical reasons. Primary Endpoint: Marker identification rate of metastatic axillary LNs using US-US fusion (VS), confirmed by radiography of the excised specimen post-TAS. Secondary Endpoints: 1) Marker identification rate at NAC completion via US-US fusion. 2) Time required for marker identification via fusion imaging. 3) Number of metastatic LNs retrieved via TAS and ALND. 4) FNR of TAS (i.e., cases with metastases found only in ALND among those with any positive nodes). Target Sample Size: Assuming a 95% expected rate and an 83% threshold, a one-sided test with 2.5% significance and 80% power requires 58 patients. Allowing for a 5% dropout rate, the target enrollment is 62 patients. Citation Format: M. Futamura, S. Junta, I. Kazuhiro, S. Takehiko, K. Keitaro, N. Shogo, Y. Miwa, N. Akira, O. Mai, M. Nobuhisa, U. Takayoshi, A. Sadako. A prospective multicenter study on the clinical utility of virtual sonography for metastatic axillary lymph nodes during neoadjuvant chemotherapy in breast cancer patients (FUSION-03) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-07-05.

Axillary surgery after neoadjuvant chemotherapy in breast cancer patients downstaging from cN+ to ycN0

Benign as well as malignant tumour tissues of the breast demonstrate higher fluorescence intensity (FI) than normal breast tissue after application of a photosensitiser. As a follow-up study, we evaluated the FI of metastatic sentinel lymph nodes and metastatic axillary lymph nodes compared to nonmetastatic sentinel and axillary lymph nodes in patients with breast cancer. In all, 11 patients received 30 mg 5-aminolevulinic acid (ALA) kg−1 bodyweight orally 3 h prior to surgery. The sentinel lymph node was marked with Nanocoll® preoperatively and with a blue dye intraoperatively. Tumour excision, excision of the sentinel lymph node and an axillary lymph node dissection were performed during the same surgical session. The operation site was illuminated with blue light (400 nm) to obtain macroscopic tissue characterisation of fluorescence. Tissue samples were stored protected from light, and analysed using a fluorescence microscope. Results were correlated with histopathology. In all, 14 sentinel lymph nodes, seven axillary lymph nodes and seven primary tumours were analysed. Metastatic sentinel lymph nodes demonstrated a statistically significant higher FI than nonmetastatic sentinel lymph nodes (2630 vs 526, P<0.0001). The FI of metastatic sentinel lymph nodes, of metastatic axillary lymph nodes and of the primary tumour were comparably high, and were statistically significantly higher compared to the normal mammary tissue. Intraoperatively, only in a few cases, it was possible to recognise the metastatic sentinel lymph node macroscopically with blue light. Our study indicates that photodynamic diagnosis with ALA has a potential in the diagnosis and detection of the sentinel lymph node in patients with breast cancer, and is worth to be further investigated and developed for intraoperative photodynamic diagnosis and possibly therapy.

The appropriateness of substituting sentinel lymph node dissection (SLND) and regional nodal irradiation (RNI) for axillary lymph node dissection (ALND) in patients with residual lymph node (LN) disease following neoadjuvant chemotherapy (NAC) is unknown. We used the National Cancer Database (NCDB) to compare survival following SLND and ALND in breast cancer patients with residual LN disease. We analyzed NCDB patients, treated between 2006 and 2014, with cT1-3, cN1, cM0 breast cancer and residual disease in 1-3 axillary LNs (ypN1) following NAC. Patients were grouped into those who received SLND (defined as removal of ≤ 4 LNs) and RNI, or ALND and RNI. Patients were matched for all patient, tumor, and treatment characteristics. We identified 1313 eligible patients in the ALND group and 304 patients in the SLND group. For the matched cohorts, SLND was associated with significantly lower survival in both univariate and doubly robust multivariable analyses (MVA) (HR 1.7, 95% CI 1.3-2.2, P < 0.001 for MVA), with estimated 5-year OS of 71%, compared with 77% in the ALND group (P = 0.01). Exploratory subgroup analyses showed that SLND was comparable with ALND in patients with luminal A or B tumors with a single metastatic LN (HR 1.03, 95% CI 0.59-1.8, (P = 0.91). Our analysis suggests that, while an ALND may not be needed for patients with limited residual nodal burden and biologically favorable tumors, SLND should not be routinely substituted for ALND in patients with ypN1 disease following NAC until its efficacy is confirmed by prospective trials.

Nanotechnology in Thoracic Surgery

BackgroundThis study aimed to determine the knowledge of major benchmark trials among Turkish general surgeons to investigate if they have adopted the results in their practice.MethodsA total of 101 general surgeons from the Turkish Federation of Breast Diseases Society (TFBDS) were asked to complete a survey that included 24 multiple-choice questions regarding the surgical practice in axillary surgery for early and locally advanced breast cancer.ResultsMost surgeons were familiar with prospective axillary surgery studies including ACOSOG Z0011 (n = 77, 76.2%), AMAROS (n = 76, 75.2%), IBCSG 23 − 01 (n = 58, 57.4%), ACOSOG Z1071 (n = 63, 62.4%), and SENTINA (n = 67, 66.3%). Among the surgeons participating in the present survey, breast surgeons (38.6%) were less likely to perform axillary lymph node dissection (ALND) in early stage patients with a 1–2 positive sentinel lymph node biopsy (SLNB) with micro- or macrometastases, as opposed to those who defined themselves as general surgeons (ALND; 36.8% vs. 63.9%, p = 0.015). Almost all surgeons suggested neoadjuvant chemotherapy (NAC) for patients presenting with T4 (94.8%) or N2-3 disease (92.0%), whereas almost half of the surgeons (40.5%) always proceeded with NAC in patients with clinically node-positive cN1 breast cancer. Overall, 86.1% of surgeons performed SLNB in patients whose axilla became clinically negative after NAC. More than half of the surgeons (55.2%) preferred blue dye as the SLNB technique and 37 (42.5%) used the combined method. Among 87 surgeons, 24.1% (n = 21) always, 39.1% (n = 34) sometimes, and 36.8% (n = 32) never preferred clip marking of axillary metastatic lymph nodes before NAC, whereas 56.4% performed targeted axillary dissection (TAD) after NAC. In cN+ patients before NAC, the majority of surgeons (74.3%) did not perform ALND in patients with at least three lymph nodes removed and SLNB negative. Of note, more than half of the surgeons (51.5%) did not perform ALND in the presence of isolated tumor cells or micrometastases among the three SLNs as long as regional nodal irradiation was received. However, 54.5% of the patients routinely underwent ALND in the presence of macrometastatic residual nodal disease after NAC.ConclusionDeescalating strategies in axillary surgery have been increasing in both initially clinically node-negative and-positive breast cancers as long as nodal radiation is provided.

Introduction: Sentinel lymph node (SLN) staging is currently used to avoid complete axillary lymph node dissection (ALND) in breast cancer (BC) patients. The SLN is the only site of axillary metastasis (MTS) in ≥60% of cases. Recently, a randomized controlled trial (Z0011) comparing SLN biopsy (SLNB) alone with SLNB followed by ALND in patients with 1-2 SLNs+ demonstrated no significant statistical difference in relapse and overall survival (OS) rates among the two different groups. However, this study had some limitations: small tumor size (≤2cm in 70% of cases), frequent presence of only microMTS in SLN (40%), prevalent use of “whole breast” adjuvant radiotherapy (&amp;gt;90%). Given these considerations, the SINODAR-ONE study started in April 2015. Objectives: The aims are to assess whether ALND omission in BC patients with 1-2 SLNs+ is associated with worse survival and/or increased rate of regional/distant relapse. Thus evaluating whether SLNB is or is not inferior to ALND. Primary endpoint is OS. Secondary endpoints are disease-free survival (DFS) referring to distant MTS and loco-regional recurrence. Methods: Patients received either mastectomy or conservative surgery plus radiotherapy. They all underwent SLNB and were randomly divided into two arms of treatment: standard (SLNB plus ALND) or experimental treatment (only SLNB). According to multidisciplinary evaluation, patients could undergo additional adjuvant radiotherapy, chemo- and/or hormonal therapy, or no further therapy. Eligibility criteria: age 40-75 years; primary invasive T1-T2 tumor; axillary nodes cN0; no more than 2 macro-metastatic SLNs; no distant MTS; no neo-adjuvant therapy; no previous invasive BC. Exclusion criteria: in situ, inflammatory, contralateral BC; micro-metastatic SLNs; pregnancy or breast feeding; comorbidity impeding adjuvant therapy. All analyses were performed both on all patients according to the Intention-To-Treat principle and excluding those patients who did not receive the axillary treatment randomly assigned. Statistical analysis: OS and DFS were calculated using the Kaplan-Meier Product Limit Estimator and differences between arms were assessed with the log-rank test. Results: The enrollment of patients ended in April 2020 with a total of 889 cases (443: standard arm; 446: experimental arm). In April 2021, we conducted a preliminary analysis on 889 patients. We found the two groups homogeneous for epidemiologic characteristics (age and menopausal status), tumor characteristics (tumor size, pTNM, immunohistochemistry, histology, grading, vascular and lymphatic invasion), and adjuvant therapies. The majority of patients (77.2%) received breast conserving surgery, while 22.8% of patients underwent mastectomy. A median of 2 SLNs were removed in both arms. Overall, only 3 micro-metastatic SNLs were found (1 in the standard arm and 2 in the experimental arm). Conclusion: In sum, OS rate is 99.1% and 99.3% in the standard and experimental arm, respectively; DFS rate is 96.8% and 95.9% in the standard and experimental arm, respectively. After a median follow-up of 36 months, there has been only one axillary recurrence in the experimental arm. Additionally, we found seven distant relapses in both arms; four and three deaths in the standard and experimental arm, respectively. Citation Format: Damiano Gentile, Wolfgang Gatzemeier, Erika Barbieri, Andrea Sagona, Alberto Bottini, Valentina Errico, Alberto Testori, Marta Scorsetti, Giuseppe Canavese, Corrado Tinterri. Preservation of axillary lymph nodes compared to complete dissection in T1-T2 breast cancer patients presenting 1-2 metastatic sentinel lymph nodes. A multicenter randomized clinical trial. Sinodar One [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 GS4-05.