IntraOperative UltraSound Guided vs Wire Guided vs Magnetic Seed Guided Breast-Conserving Surgery for Non-palpable Tumors

Not Applicable

Not yet recruiting

• Conditions: Breast Cancer; Breast-Conserving Surgery

• Registration Number: NCT07185568
• Lead Sponsor: Istituto Oncologico Veneto IRCCS

Brief Summary

This is a multi-center, randomized, open-label clinical trial that will enroll 1302 adult patients with non-palpable breast lesions. Participant eligible for the study will be randomized in a 1:1:1 ratio to one of the pre-surgery lesion localization: IOUS HydroMark™ (experimental arm A), magnetic Sirius Pintuition Seed® (experimental arm B) and the wire localization technique (control arm). The randomization will be stratified by lesion type (solid non-palpable (type B); non-solid non-palpable (e.g., microcalcification clusters, architectural distortive areas) (type C); post-NACT residual lesions (type D), and clinical center.

Detailed Description

Breast-conserving surgery is the gold standard treatment for early breast cancer, since it has shown disease-free survival rates equivalent to those of mastectomy, offering the advantages of cosmetic outcome preservation, a better quality of life and a decrease in psychological morbidities. These important aspects, along with the general goal of reducing the extent of surgical excisions, have increased the need for an effective pre- surgery lesion localization and surgical guidance techniques. Reported rates of margin involvement after BCS range from 10 to over 40%, and positive resection margin is one of the strongest predictive factors for local recurrence. This event requires additional surgical procedures (re-excision or mastectomy) and/or radiotherapy boost, leading to higher healthcare costs and worse cosmetic outcomes, in addition to further stress for surgeons and patients.

Wire localization (WL) is the most used method for non-palpable breast lesions, with clear margins reported in a range of 70.8%-87.4% of cases. Recognized advantages of wires are the widespread availability and the moderate price. Moreover, wires emit no ionizing radiation and can be stored safely. Although WL is highly effective, with approximately 2.5% of unsuccessful wire localizations associated with multiple lesions, small lesions, lesions containing extensive microcalcifications and small surgical specimens, it still yields several disadvantages. The procedure is unpleasant and causes patient discomfort; wire migration within the breast, and more infrequently outside the breast, has also been reported. The hookwire can be transected during the surgery, with pieces being retained in the breast post- operatively. Finally, this localization approach requires adequate coordination between trained breast radiologists and surgeons because the wire placement has to occur on the day of surgery to avoid displacement. This limitation can lead to inconvenience and delay in the operating room or suboptimal localization. Moreover, wire localization could limit the surgical approach and cause a potential worse cosmetic outcome; the placement route of the wire, chosen by the radiologist, often dictates incision choice for the surgeon who then has to follow the wire's course during dissection.

Magnetic seed is a relatively new localization technology for non-palpable breast lesions. The localization system includes a magnetic seed, that may be positioned using a needle under radiological guidance days, weeks or months before the surgical procedure and it offers a demonstrated reduced risk of migration compared to wire-guided localization. This method has no radiation emission, so that the signal does not decay over time, and it does not require a destruction protocol in comparison to radioactive seeds. Literature describes magnetic guidance as safe and feasible. The magnetic seeds may be seen on breast imaging including ultrasound, mammography, and tomosynthesis. MRI is not contraindicated although a degree of movement artifact would be expected as with any metal clip. The magnetic device has the potential of localizing lesions accurately, and may reduce re- excision rates, pain and excision specimen weight. The main disadvantages of magnetic seed are the high costs of devices and the creation of MRI artefacts. Nevertheless, magnetic seed localization still seems to be one of the most promising recent technological innovation in BCS. The Sirius Pintuition Seed® is a permanent magnetic seed that accurately marks the tumor and helps the procedure of surgical removal from any direction. The magnetic seed is robust and is encapsulated in high-grade, nickle-free biocompatible titanium. Sirius Pintuition is a wire-free localization technology designed to provide navigational guidance through a dedicated software that offers directional guidance using audio and visual feedback.

All the traditional breast localization techniques may be described as essentially blind, since they do not allow the direct visualization of breast lesions during surgery. In 1988 Rifkin et al. firstly described ultrasound (US) as a tool for localizing breast masses during surgery and facilitating their surgical excision. Many other successful experiences followed, for palpable and non-palpable BC and even for post neoadjuvant residual lesions. A recently published prospective study demonstrated the efficacy of IOUS for all the types of BC lesions. Nevertheless, systematic US performance during BCS is still regarded as a new developing concept, being underused in this surgical oncology field. Intra-operative ultrasound-guided surgery (IOUS) is the only technique allowing a real-time visualization of BC and resection margins running control during all surgical phases. Previous series reported glaring advantages over the other techniques both for oncological and cosmetic outcomes.

HydroMarkTM clip has the potential to amplify the efficacy of IOUS, since the clip is easy to view, and it allows an easier guide in every phase of surgery. The HydroMarkTM marker hydrogel hydrates to provide up to 12 months of ultrasound visibility and it offers permanent stereotactic, tomosynthesis, and X-ray visibility. Moreover, it does not contraindicate Magnetic Resonance Imaging (MRI). It is demonstrated that the clip offers a permanent MRI visibility without generating any artefact, while it results uniquely distinguishable on a T2 sequence for up to 12 months. The results of a recently published study described the procedure of localization the clip under ultrasound as a faster and more comfortable procedure for the patient compared to the wire localization. HydroMark clip costs are slightly higher than a stadard stereotactic clip. The use of IOUS with HydroMark clips have the potential to improve patients' experience, with a particular attention in preserving the cosmetic aspect, leading to an improved quality of life in this specific population. According to the available scientific evidences IOUS technique allows excellent oncological and cosmetic outcomes and contribute to organizational aspects improvement in breast-conserving surgery compared with the traditional methods of wire-guide surgery. Moreover, it seems to be cost-saving with respect to magnetic seeds techniques, without limiting the possibility of further MRI evaluations of the patients.

However only limited literature is available and clinical studies to evaluate safety and effectiveness involving these devices have been carried out on small numbers of patients and not randomized. No strong evidence of comparison between these techniques is available, especially for non-palpable BC lesions. To our knowledge, the only randomized clinical trial available analyzes the performances of IOUS only taking into consideration palpable lesions. Therefore, more robust randomized trials are needed in order to provide a complete picture of the real effectiveness of these new promising techniques.

The aim of this prospective trial is to identify which of these three techniques offers the best surgical guidance for non-palpable BC lesions excision in terms of surgical, oncological, cosmetic and cost-effectiveness outcomes.

Study Timeline

• Status Verified: 2025-09
• Study First Submitted: 2025-09-05
• Study First Submitted QC: 2025-09-15
• Last Update Submitted: 2025-09-15
• Study First Posted: 2025-09-22
• Last Update Posted: 2025-09-22
• Study Start: 2025-09-30
• Primary Completion: 2027-09-30
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 1302

Inclusion Criteria

• Patients with non-palpable breast cancer candidate for breast-conserving surgery;
• Female patients;
• Patients aged ≥ 18 years;
• Patients with histologic diagnosis of cT1-T2 invasive BC or ductal carcinoma in situ;
• Patients amenable for BCS after neoadjuvant chemotherapy;
• Patients who are able to give informed consent.

Exclusion Criteria

• Pregnancy or lactation;
• Patients with locally advanced disease or metastatic disease;
• Patients with palpable breast carcinoma;
• Patients candidate for mastectomy;
• Patients who are unable to give informed consent
• Patients candidate for mastectomy.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Involved resection margins.	Through study completion, an average of 2 years	Compare the efficacy of the IOUS HydroMark™ and magnetic Sirius Pintuition Seed® versus the wire localization technique in terms of involved resection margins. Positive margin rate, defined as the number of patients with ink on invasive cancer or ductal carcinoma in situ with a resection margin \< 2mm out of the total number of enrolled patients.

Secondary Outcome Measures

Name	Time	Method
Postoperative complications	Through study completion, an average of 2 years	Evaluate the 3 techniques in terms of postoperative complications, assessed according to the Clavien-Dindo classification system.
Re-excision rate	Through study completion, an average of 2 years	Evaluate the 3 techniques in terms of re-excision rate, defined as the number of patients who need to be re-operated after initial conservative surgery out of the total number of operated patients. Reoperation was recommended for any resection margin \< 2 mm.
Target lesion removal rates	Through study completion, an average of 2 years	Evaluate the 3 techniques in terms of target lesion removal rates, defined as the number of lesions that were totally removed without involved margins after first surgical excision
Closest margin width	Through study completion, an average of 2 years	Evaluate the 3 techniques in terms of closest margin width, calculated as the minimal distance between the tumor edge and the closest resection margin
Calculated resection ratio (CRR)	Through study completion, an average of 2 years	Evaluate the 3 techniques in terms of calculated resection ratio (CRR), defined as the surgical specimen volume related to the optimal resection volume (ORV), which represent the theoretical minimum volume needed to remove the tumor with a 1 cm clear margin
Tumor and surgical specimen volume ratio	Through study completion, an average of 2 years	Evaluate the 3 techniques in terms of tumor and surgical specimen volume ratio: the tumor volume will be calculated considering the tumor as an elliptical sphere using the ellipsoid equation V = 4/3 pi × a × b × c, where a, b and c are the lengths of the semi-diameters of the tumor; the surgical specimen volume will be the sum of the main specimen and the cavity shaving margin volumes; these will be calculated as volumes of a rhombic prism, using the formula V = d1 × d2 × h/2, where d1, d2 and h are the diameters of the main specimen and of each single cavity shaving margin. Volumes that will be excised only for cosmetic reasons will not be considered.
BREAST-Q score	Through study completion, an average of 2 years	Evaluate the 3 techniques in terms of BREAST-Q score based on BREAST-Q BCT module, a questionnaire designed to evaluate patient satisfaction in two domains: satisfaction with breasts and satisfaction with care.
Resource consumption and estimation of costs	Through study completion, an average of 2 years	Evaluate the 3 techniques in terms of resource consumption and estimation of costs. Costs will be calculated in euros (€) for eachparticipant in the clinical trial. The economic evaluation is performed as a within-trial analysis, indicating that only costs and effects that accumulate within the trial length are included.
Number of re-excisions within the first 6 months following the first surgery	Through study completion, an average of 2 years	Evaluate the 3 techniques in terms of number of re-excisions within the first 6 months following the first surgery.
EQ-5D-5L	Through study completion, an average of 2 years	The patient-related effectiveness measures are health related quality of life (HRQoL). HRQoL is estimated using the EuroQol 5-dimension 5-level (EQ-5D-5L)

Trial Locations

Locations (5)

Azienda Ospedaliera San Giovanni Addolorata; 🇮🇹 Roma, RM, Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS; 🇮🇹 Roma, RM, Italy

AOU Policlinico di Modena; 🇮🇹 Modena, Italy

ASL2 Abruzzo, Ospedale "Gaetano Bernabeo", Ortona; 🇮🇹 Ortona, Italy

Istituto Oncologico Veneto IRCCS; 🇮🇹 Padua, Italy