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

NCT07185568 | Not Yet Recruiting

• 1 other identifier: IOV-BC-1-2024 MANOLA
• Study Type: interventional
• Target: 1,302
• Locations: 1 country
• Sites: 5

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.

Conditions

Breast-Conserving Surgery; Breast Cancer

Keywords

IntraOperative UltraSound guided; Wire guided; Magnetic Seed guided

Outcome Measures

Primary Outcomes (1)

• Involved resection margins.

  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.

  Through study completion, an average of 2 years

Secondary Outcomes (10)

• Postoperative complications

  Through study completion, an average of 2 years

• Re-excision rate

  Through study completion, an average of 2 years

• Target lesion removal rates

  Through study completion, an average of 2 years

• Closest margin width

  Through study completion, an average of 2 years

• Calculated resection ratio (CRR)

  Through study completion, an average of 2 years

Study Arms (3)

IntraOperative Ultrasound (IOUS) HydroMark™

EXPERIMENTAL

It is an advanced localization technique for non-palpable breast lesions, leveraging real-time ultrasound guidance combined with an ultrasound-visible tissue marker (HydroMark™) to facilitate precise tumor resection during breast-conserving surgery (BCS).

Procedure: IOUS HydroMark™

Magnetic Sirius Pintuition Seed®

EXPERIMENTAL

It is an advanced, wire-free localization system designed for precise surgical guidance in non-palpable breast lesions. This technology utilizes a small, permanent magnetic seed that can be implanted into the tumor days, weeks, or even months before surgery, offering greater flexibility compared to traditional wire localization.

Procedure: Magnetic Sirius Pintuition Seed®

Wire localization

ACTIVE COMPARATOR

It is the most widely used preoperative technique for guiding the surgical removal of non-palpable breast lesions. This method involves the insertion of a thin hooked wire into the lesion under radiological guidance (ultrasound, mammography, or stereotactic guidance) on the day of surgery. The wire serves as a physical guide for the surgeon, ensuring precise excision of the target lesion.

Procedure: Wire localization (WL)

Interventions

Magnetic Sirius Pintuition Seed® PROCEDURE

The Pintuition Localization System is intended as a magnetic soft tissue localization system. The magnetic Pintuition Seed is indicated for preoperative percutaneous implantation into soft tissue (glandular, fibrous or fatty tissue of breast; lymph nodes in the axillary and inguinal region; subcutaneous tissue and skeletal muscle tissue) for temporary marking (\<180 days) of a tissue of interest (e.g. tumor or a suspected lesion) indicated for surgical removal. Using the Pintuition Detector as magnetic guidance or, alternatively, image guidance (ultrasound or x-ray), the Pintuition Seed can be intra-operatively localized and removed together with the tissue of interest.

Magnetic Sirius Pintuition Seed®

Wire localization (WL) PROCEDURE

Single-use, repositionable needle for preoperative localization of breast nodules with a single hook, equipped with a depth limiter. Designed for the localization of non-palpable breast lesions in the preoperative phase. It includes a fixation clamp to stabilize the positioning of the wire.

Wire localization

IOUS HydroMark™ PROCEDURE

IOUS HydroMarkTM allows marking the tissue during percutaneous breast biopsy. This is a sterile, single-use marker made of resorbable hydrogel, which expands upon contact with bodily fluids and is then gradually absorbed. The hydrogel is visible on ultrasound. Inside the hydrogel, there is a metallic spiral (titanium/steel) that remains permanently visible in radiographic and MRI examinations even after the hydrogel has been fully absorbed. The HydroMARK Breast Biopsy Site Marker is made of a resorbable hydrogel that expands with fluid and is then resorbed. The hydrogel material is visible under ultrasound. Embedded in the hydrogel is a coiled metallic wire that will be permanently visible under x-ray and MRI when the hydrogel is resorbed. The HydroMARK Biopsy Site Marker is a permanent implant and is not intended to be removed unless the marked tissue is determined to require surgical removal. The marker is supplied pre-loaded in applicator devices designed.

IntraOperative Ultrasound (IOUS) HydroMark™

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Istituto Oncologico Veneto IRCCS: lead

Study Sites (5)

Azienda Ospedaliera San Giovanni Addolorata

Roma, RM, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, RM, Italy

Location

AOU Policlinico di Modena

Modena, Italy

Location

ASL2 Abruzzo, Ospedale "Gaetano Bernabeo", Ortona

Ortona, Italy

Location

Istituto Oncologico Veneto IRCCS

Padua, 35128, Italy

Location

Related Publications (5)

• Krekel NM, Haloua MH, Lopes Cardozo AM, de Wit RH, Bosch AM, de Widt-Levert LM, Muller S, van der Veen H, Bergers E, de Lange de Klerk ES, Meijer S, van den Tol MP. Intraoperative ultrasound guidance for palpable breast cancer excision (COBALT trial): a multicentre, randomised controlled trial. Lancet Oncol. 2013 Jan;14(1):48-54. doi: 10.1016/S1470-2045(12)70527-2. Epub 2012 Dec 4.

  PMID: 23218662 BACKGROUND

• Rubio IT, Esgueva-Colmenarejo A, Espinosa-Bravo M, Salazar JP, Miranda I, Peg V. Intraoperative Ultrasound-Guided Lumpectomy Versus Mammographic Wire Localization for Breast Cancer Patients After Neoadjuvant Treatment. Ann Surg Oncol. 2016 Jan;23(1):38-43. doi: 10.1245/s10434-015-4935-z. Epub 2015 Oct 29.

  PMID: 26514120 BACKGROUND

• Volders JH, Haloua MH, Krekel NM, Negenborn VL, Kolk RH, Lopes Cardozo AM, Bosch AM, de Widt-Levert LM, van der Veen H, Rijna H, Taets van Amerongen AH, Jozwiak K, Meijer S, van den Tol MP. Intraoperative ultrasound guidance in breast-conserving surgery shows superiority in oncological outcome, long-term cosmetic and patient-reported outcomes: Final outcomes of a randomized controlled trial (COBALT). Eur J Surg Oncol. 2017 Apr;43(4):649-657. doi: 10.1016/j.ejso.2016.11.004. Epub 2016 Nov 23.

  PMID: 27916314 BACKGROUND

• Esgueva A, Rodriguez-Revuelto R, Espinosa-Bravo M, Salazar JP, Rubio IT. Learning curves in intraoperative ultrasound guided surgery in breast cancer based on complete breast cancer excision and no need for second surgeries. Eur J Surg Oncol. 2019 Apr;45(4):578-583. doi: 10.1016/j.ejso.2019.01.017. Epub 2019 Feb 1.

  PMID: 30737056 BACKGROUND

• Ferrucci M, Milardi F, Passeri D, Mpungu LF, Francavilla A, Cagol M, Saibene T, Michieletto S, Toffanin M, Del Bianco P, Grossi U, Marchet A. Intraoperative Ultrasound-Guided Conserving Surgery for Breast Cancer: No More Time for Blind Surgery. Ann Surg Oncol. 2023 Oct;30(10):6201-6214. doi: 10.1245/s10434-023-13900-x. Epub 2023 Aug 22.

  PMID: 37606837 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Massimo Ferrucci, MD PhD

  Veneto Institute of Oncology IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Massimo Ferrucci, MD PhD

CONTACT

0498215588; massimo.ferrucci@iov.veneto.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: September 5, 2025
• First Posted: September 22, 2025
• Study Start: May 4, 2026
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 24, 2026

Record last verified: 2026-03

Locations

IT (5)