Axillary Staging in Early Breast Cancer: SNB vs PET/MRI

Study Overview
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Brief Summary
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The gold standard of surgical treatment for patients with early breast cancer (BC) is breast conservation and sentinel node biopsy (SNB). Ongoing randomized trials are evaluating to omit surgery at all when axillary imaging is negative. However, the available diagnostic tools still have several limitations in accuracy. Combining the specificity of PET, with the superior sensitivity of MRI, hybrid PET/MRI might be a non-invasive, one-stage, operator-independent imaging method to accurately define nodal status and, whenever negative, might replace surgery for axillary staging. The project includes patients with <3 cm BC without overt nodal involvement who will undergo PET/MRI prior to surgery. The primary aim is to compare the staging power between SNB and PET/MRI in detecting axillary lymph node macrometastases (>2 mm). Additionally, general concordance and diagnostic accuracy of PET/MRI vs SNB, eventual correlation with BC molecular subtypes and MRI findings will be evaluated.

Detailed Description
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SNB is the gold standard for axillary staging in early BC patients. Although being a minimally invasive, it is time consuming both for surgeon and pathologist, it may add a further scar and is not free from complications: seroma, limitation of shoulder movement, nerve injury, lymphedema. To date, patients undergoing breast conserving surgery (BCS) with 1 to 2 positive nodes can be treated with SNB alone (ACOSOG Z011 trial NCT00003855[2-4]) and researchers are evaluating within large randomized trials to even omit surgery at all when axillary imaging is negative (SOUND (Sentinel node biopsy vs Observation after axillary Ultra-souND), PI and Study Chair Dr.O.Gentilini,MD, NCT02167490 and INSEMA (Intergroup-SEntinel-MAmma) trial NCT02466737. While the role of surgery is decreasing, the role of preoperative imaging is increasing. In the future, imaging might even replace surgery in the axillary staging of BC patients, still providing an appropriate level of information to guide medical treatments which are more and more tailored on biology rather than on nodal status. In this context, an unmet need is to achieve the most accurate preoperative imaging assessment of the axilla in order to decide the appropriate treatment for each patient. The hypothesis of this project is that PET/MRI might provide a single, one-stage, non-invasive, operator independent imaging modality in patients with small BC allowing to select the proper treatment for patients. PET/MRI is a relatively new imaging tool and its field of application is still object of scientific speculation.

Official Title
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Targeting the Future of Axillary Staging in Early Breast Cancer: A Comparative Study: Sentinel Node Biopsy vs PET/MRI

Conditions
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Breast Cancer, Sentinel Lymph Node, Early-stage Breast Cancer

Intervention / Treatment
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* Diagnostic Test: PET/MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: signed Informed Consent age > 18 cT < 3 cm non palpable lymph nodes no suspicious nodes at A-US (Axillary- ultrasound) candidate to mastectomy or breast conserving surgery and BLS (Sentinel Node Biopsy) Exclusion Criteria: pregnancy distant metastasis inflammatory cancer claustrophobia allergy to contrast agent severe renal insufficiency

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PET/MRI<br>Patients with early breast cancer up to 3 cm without overt nodal involvement who are candidates to upfront surgery | Diagnostic Test: PET/MRI<br>* A consecutive cohort of 247 patients with early BC and no suspicious nodes at both clinical and A-US evaluations and candidates to upfront surgery and SNB will be recruited<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SNB vs PET/MRI | Results from SNB will be compared to results from PET/MRI y results from SNB will be available and compared to results of preoperative PET/MRI | Within 1 month after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A secondary outcome is the staging power of PET/MRI compared to preoperative A-US (Axillary Ultrasound) | Study will focus on a subgroup of patients having one or two uncertain but no suspicious axillary nodes for which SNB is still indicated. Patient population will be divided into two cohorts: those with completely normal axillary lymph node at A-US and those with 1-2 axillary nodes with uncertain ultrasound features. These two groups will be analysed independently. The PET/MRI and A-US results will be compared to each other and ultimately to final pathology, calculating the concordance rate in terms of positive versus negative nodes and number of positive nodes detected by each method. The staging power of both preoperative exams will be evaluated by considering how many times the results from PET/MRI or A-US could have indicated the most appropriate axillary treatment according to pathological findings. | At 12 months | 
| Correlation between PET/MRI parameters and breast cancer prognosis | Eventual associations between PET/MRI morphological and functional parameters with tumour prognostic features will be investigated. | 0 and 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PET/MRI, sentinel node biopsy, early breast cancer