Abstract PS5-07-05: 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 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.