Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Carcinoma

Breast Neoplasms

Carcinoma in Situ

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Patients are randomised for preoperative lesion localization with either radioactive seed localization (RSL) or wire-guided localization (WGL).

In this arm 205 patients will have RSL performed. The radioactive seed is introduced through a gauge needle using standard ultrasound guidance. Once guided to the nonpalpable breast lesion, the seed is deployed into the breast tissue by advancing a stilette in the needle. The exact location is confirmed by mammography. The nonpalpable lesion is located during the operation with a handheld gamma probe, identical to the one used for the sentinel node procedure. The surgical specimen is orientated and examined at the Department of Radiology and Pathology in accordance with the existing guidelines of WGL.

Patients are randomised for preoperative lesion localization with either radioactive seed localization (RSL) or wire-guided localization (WGL).

In this arm 205 patients will have WGL performed. Guided by ultrasound or mammography a flexible wire is introduced into the breast by the radiologist just before the operation. The tip of the wire must mark the nonpalpable lesion, and correct localization is verified by mammography. The surgeon uses the wire and mammography as a guide during the operation. The surgical specimen is orientated and examined at the Department of Radiology and Pathology in accordance with the existing guidelines of WGL.

Localization of nonpalpable breast lesions with Radioactive seed localization

Radioactive seed localization (RSL)

Localization of nonpalpable breast lesions with Wire-guided localization

Wire-guided localization (WGL)

Niels Kroman, Professor

Each year the Danish mammography-screening programme identifies a large number of patients with small non-palpable breast cancers or precancerous lesions. The majority of these patients are suitable for breast conserving surgery (BCS). The object of BCS is to remove the suspicious lesion completely without removing excess healthy breast tissue. To obtain this accurate lesion localization is essential.

Until today the standard procedure in Denmark has been wire guided localization (WGL). Although the method has been utilized for a number of years it has several disadvantages. Often inaccurate lesion localization leads to incomplete lesion removal (positive margin) and subsequently reoperation. It can postpone the additional systemic treatment, offered after the operation. Other disadvantages are poor cosmetic outcome and inconvenient planning for the patient and the departments involved. The wire needs to be placed on the day of the operation, which decreases the flexibility of the procedure.

The purpose of this study is to test a new method named radioactive seed localization (RSL). The method uses a small titanium seed containing radioactive iodine. It will be placed in the centre of the lesion, and during the operation, the surgeon can locate it with a handheld gamma probe. The seed can be placed a few days in advance, which means a more flexible course of treatment. The method seems promising with regards to reoperation rates, but it needs further testing.

Hypothesis:

RSL is a more accurate method, for localization of nonpalpable breast lesions, than WGL. Using RSL obtains, to a great extent, adequate negative margins, resulting in a reduced number of re-operations.

The study will be performed as a randomised clinical trial, where the two methods will be compared to each other. The trial will be performed at the department of breast surgery at Rigshospitalet and include patients with nonpalpable breast lesions. Besides reoperation rates, duration of the surgical procedure and the amount of removed breast tissue will be compared.

Localization of Nonpalpable Breast Lesions

A Randomized Study of Localization of Nonpalpable Breast Lesions - RSL vs WGL

Data will be presented in a international peer review article.

Rigshospitalet, Denmark

Behaviors and Mental Disorders

Quality of Life

Wire guided localization (WGL) is considered the standard method for intraoperative localization of non-palpable breast lesions, chosen by many centers worldwide. It involves the placement of a wire or barbed needle that is percutaneously introduced into the lesion using a guide. It is cost-effective, easy to place guided by ultrasound or stereotaxis, allows for repositioning in case of error, and its safety and efficacy have been widely demonstrated in the literature.

The use of intraoperative ultrasound (IOUS) is an effective method that is controlled by the surgeon and does not require the involvement of other departments or preoperative invasive procedures. IOUS has been introduced into clinical practice as a tool for visualizing non-palpable tumors, demonstrating the detection of nearly 100% of lesions, and a rate of negative margins and re-excision similar to WGL. One of the challenges of the technique in ultrasound-guided surgery arises when the tumor is \<5mm, making it difficult to visualize by ultrasound, or when there are microcalcifications not visible by ultrasound.

Radioactive seeds are composed of a titanium capsule with an I-125 filament inside. They have low radioactivity, which can range from 7 to 200 μCi. During surgery, the seeds are detected using a portable gamma ray detection probe typically used for sentinel lymph node biopsy, configured to detect an I-125 source (27 keV). This probe has a wide detection range through tissue (\>10 cm), currently offering the greatest detection range compared to other available localization devices. Radioactive seed localization (RSL) require coordination between the radiology and nuclear medicine departments for marking. The results in terms of lesion localization and margin involvement rates are comparable to WGL.

If assigned to the WGS, the marking will be performed by the radiologist on the day prior to the intervention.

Wire-guided surgery

If assigned to the RSL, the marking will be performed by the radiologist on the day prior to the intervention. The handling and traceability will be done by the nuclear medicine physician.

Radioactive seed localization

If the patient is assigned to the Intraoperative ultrasound localization (IOUS), no further procedures will be necessary until surgery. Subsenquently, the primary surgery will be performed.

Intraoperative ultrasound localization

Eduard Mension, MD PhD

Ines Torras

Eduard Mension

The goal of this clinical trial is to compare Quality of Life and cosmetic outcomes in Breast Conservative Carcer surgery depending on localization method (intraoperative Ultrasound, wire and radioactive seed).

Participants will be randomly assigned to one of the three proposed arms, and the primary surgery will be performed.

INTRODUCTION:

The surgery for breast cancer is increasingly emphasizing cosmetic outcomes, body image, and the quality of life (QoL) of patients. Survival is the top priority; however, other concerns or problem areas may arise, such as dissatisfaction with body image. All of this has implications for QoL, self-esteem, relationships, and sexual functionality. One of the challenges of breast conservative surgery (BCS) is suboptimal cosmetic results, which can be observed in up to 40% of patients in some series. Factors influencing the cosmetic outcome include patient characteristics such as weight or breast density, the volume of the tumor removed, the tumor's location in the breast, wound complications, and the dose and schedule of radiotherapy. Therefore, the use of low-visibility incisions, precise tumor resection, and the introduction of oncoplastic techniques have revolutionized the surgical management of these patients.

The localization of the lesion is a key point for surgical resection. Advancements in imaging diagnostic methods and molecular classification have led to a reevaluation of surgical approaches. The widespread use of mammography as a screening method for breast cancer has resulted in an increase in the detection of non-palpable breast lesions, necessitating the search for tools to detect these lesions. The intent of surgery should always be both radical and effective, meaning achieving the removal of the loco-regional disease. The main challenge in breast surgery lies in striking a balance between wide excision with clear margins and a satisfactory cosmetic outcome Currently, there are multiple localization techniques available, although the evidence from comparative studies is limited. Wire guided localization (WGL) is considered the standard method for intraoperative localization of non-palpable breast lesions and is the method of choice for many centers worldwide. However, alternative localization techniques such as radioguided occult lesion localization using radioactive iodine-125 seeds (RSL) and ultrasound guided surgery (UGS) have recently been shown to reduced re-excision rates. In a systematic review comparing different localization methods, UGS reduced the percentage of involved margins and significantly decreased the reoperation rate and surgical time when compared to WGL. UGS also showed a statistically significant reduction in the number of involved margins compared to RSL. All techniques were equivalent in terms of effectiveness, localization complications, and general complications. The available evidence on cosmetic outcomes and QoL in BCS according to the localization technique is limited.

We hypothesized UGS and RSL would be associated with a better QoL and cosmetic outcome compared to WGL. The aim of TRIGUIDE study was to compare the QoL and cosmetic outcomes of women who underwent BCS according the localization method.

METHOD/PROCEDURES:

All eligible patients scheduled for primary surgery with ecovisible lesions will be prospectively recruited from external Gynecology consultations. They will have attended the consultation according to the usual care pathway, after completing complementary tests and receiving a confirmed diagnosis. An ultrasound will be performed by the surgeon in the consultation to confirm the identification of the lesion. Baseline quality of life (QoL) will be assessed using the BREAST-Q questionnaire (preoperative).

The surgical procedure will be jointly decided by the surgeon and the patient and will not be modified by the study. Patients will be consecutively and randomly assigned to one of the three proposed arms. If the patient is assigned to the intraoperative ultrasound arm, no further procedures will be necessary until the surgery. If assigned to the wire or seed arm, the marking will be performed by the radiologist on the day prior to the intervention. The handling and traceability of the radioactive seed, if applicable, will be done by the nuclear medicine physician. Subsequently, the primary surgery will be performed. We will preserve the orientation of the specimen with marking sutures, such that positive resection margins could be identified and re-excised if necessary. Radiological margin assessment will be conducted during procedure and ampliations will be performed with the advice of the radiologist and the surgeon's discretion. We will undertake axillary surgery in the same session, according to international guideline. The surgical specimen will be postoperative processed and analyzed by the Pathology Department. A multi- disciplinary team will review all cases preoperatively and postoperatively, and we will administer adjuvant radio- therapy or systemic therapy according to institutional and national guidelines. Regular follow-up will be carried out by the Gynecology team, with a visit at 3-4 weeks and 12 months post-surgery.

Single-center parallel randomized Clinical Trial with three arms: intraoperative Ultrasound vs. wire vs. radioactive seed

Quality of Life and Cosmetic Outcomes of Breast-Conserving Surgery According to Localization Method

Quality of Life and Cosmetic Outcomes of Breast-Conserving Surgery According to Localization Method (TRIGUIDE Trial) - A Randomized Trial

BCCT.core is a semi-automatic software validated for the assessment of cosmetic outcomes following BCS. It provides an objective measure and has been demonstrated to correlate well to a panel of experts. BCCT.core analyses several parameters including symmetry, skin colour and scar visibility to evaluate breast cosmesis, and classifies the overall cosmetic result into four classes: Excellent, Good, Fair and Poor. However, BCCT.core does not incorporate patient self-perception of outcome and does not directly assess the volume of breast excised. Standardized clinical photographs were taken 1-year post-surgery with or without radiotherapy, as recommended by the BCCT.core software developers and assessed at the end of the data collection period by a single investigator, blinded to the identification and treatment group of the participant.

The BREAST-Q questionnaire is a specific and validated Patient-Reported Outcome Measure (PROM) for patients undergoing breast surgery designed to assess the outcomes and satisfaction of individuals, which measures health-related QoL (physical well-being, psychological and sexual) and satisfaction (satisfaction with the breast, satisfaction with the overall result and satisfaction with the care received). Each scale is scored to generate a numeric score on a scale from 0 (worst) to 100 (best). These measures were studied at baseline (preoperative) and 12 months post-surgery.

Defined by the resected breast volume minus the tumor volume

negative - no tumour cells at inked margin; or positive - tumour at the inked edge

Number of ampliations to reach negative margin status

Record the need for new surgeries, both for margin ampliation and complications

defined in min as the time from the first mammary incision to wound closure

Seroma, hematoma, infection and their management (conservative, drainage, antibiotic therapy, drainage)

Surgeon satisfaction with localization method with a Likert scale:

1. - Very dissatisfied
2. - Dissatisfied
3. - Unsure
4. - Satisfied
5. - Very satisfied

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Localization of Nonpalpable Breast Lesions	NCT01901991	Breast Cancer Carcinoma in Si...	Radioactive see... Wire-guided loc...	18 Years -	Rigshospitalet, Denmark
Quality of Life and Cosmetic Outcomes of Breast-Conserving Surgery According to Localization Method	NCT06186011	Breast Cancer	Wire-guided sur... Radioactive see... Intraoperative ...	18 Years -	Hospital Clinic of Barcelona
Localization of Nonpalpable Breast Lesions	NCT01901991	Breast Cancer Carcinoma in Si...	Radioactive see... Wire-guided loc...	18 Years -	Rigshospitalet, Denmark

Spots Global Cancer Trial Database for radioactive seed localization