Ignite Creation Date:
2025-12-24 @ 5:25 PM
Ignite Modification Date:
2026-01-01 @ 7:35 AM
Study NCT ID:
NCT07185568
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-12-16
First Post:
2025-09-05
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
IntraOperative UltraSound Guided vs Wire Guided vs Magnetic Seed Guided Breast-Conserving Surgery for Non-palpable Tumors
Sponsor:
Istituto Oncologico Veneto IRCCS
Organization:
Study Overview
Official Title:
IntraOperative UltraSound Guided Versus Wire Guided Versus Magnetic Seed Guided Breast-conserving Surgery for Non-palpable Tumors.The MANOLA Study Multi-center, Randomized, Open-label Clinical Trial
Status:
NOT_YET_RECRUITING
Status Verified Date:
2025-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MANOLA
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.
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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: