Breast Cancer, Breast Cancer - Infiltrating Ductal Carcinoma
Conditions
Keywords
Breast Cryoablation, Percutaneous Cryoablation, Minimally Invasive Treatment, Contrast-Enhanced Mammography, Early Breast Cancer
Brief summary
The goal of this clinical trial is to study cryoablation as a treatment for selected adults with localized breast cancer. Cryoablation uses very low temperatures to destroy the tumor through thin needles placed through the skin under ultrasound guidance. The main questions this study aims to answer are: * Can cryoablation completely destroy the treated breast tumor? * Is the procedure safe and well tolerated? * Can ultrasound and contrast-enhanced mammography be used to monitor the treated area after cryoablation? The study will include participants with breast cancer who cannot undergo surgery or choose not to have surgery, as well as selected postmenopausal participants with small, low-risk breast cancers. Participants will undergo ultrasound-guided cryoablation instead of surgical removal of the breast tumor. They will then have clinical examinations and imaging follow-up, including ultrasound and contrast-enhanced mammography, to assess the treated area over time. A biopsy will be performed if follow-up findings are suspicious or unclear. Other cancer treatments, such as radiation therapy or hormone therapy, will be given when indicated according to standard clinical practice.
Detailed description
CRYSTAL is a prospective, single-center, single-arm interventional study evaluating ultrasound-guided percutaneous cryoablation for the treatment of selected patients with localized breast cancer. The study includes two clinical cohorts. Cohort A includes patients with localized breast cancer who are not suitable candidates for surgery because of age, comorbidities, or other clinical factors, as well as patients who decline surgery after appropriate multidisciplinary evaluation and counseling. Cohort B includes selected postmenopausal patients with small, unifocal, biologically low-risk breast cancers considered suitable for a minimally invasive treatment strategy. All participants will have histologically confirmed breast cancer before treatment, with assessment of relevant prognostic and predictive tumor markers. Eligibility and treatment strategy will be discussed within the multidisciplinary breast unit. Cryoablation will be performed percutaneously under ultrasound guidance. The procedure will aim to obtain complete coverage of the tumor by the ice ball with an appropriate safety margin while protecting the skin, chest wall, and other adjacent structures. Participants will undergo clinical and imaging surveillance after treatment. Ultrasound and contrast-enhanced mammography (CEM) will be the principal imaging techniques used to assess the ablation area and detect possible residual or recurrent disease. Breast magnetic resonance imaging may be used when CEM is contraindicated, not feasible, or inconclusive. Tissue sampling will be performed when clinical or imaging findings are suspicious or inconclusive. The primary objective is to evaluate complete local tumor ablation approximately 6 months after cryoablation. Secondary objectives include technical success, procedure-related adverse events, residual disease, need for repeat cryoablation or subsequent surgery, procedural characteristics, quality of life, and local recurrence during follow-up. Adjuvant systemic treatment and/or radiation therapy will be administered when clinically indicated according to multidisciplinary assessment and standard clinical practice. Participants will be followed for up to 24 months after cryoablation.
Interventions
PROCEDUREUltrasound-Guided Percutaneous Cryoablation
Percutaneous cryoablation of the primary breast tumor will be performed under local anesthesia and real-time ultrasound guidance. One or more cryoprobes will be positioned within the tumor according to lesion size and geometry. Freeze-thaw cycles will be performed to create an ice ball encompassing the tumor with an adequate safety margin, while protecting the skin and adjacent structures when necessary. Technical success and procedure-related adverse events will be recorded.
Sponsors
Ospedale Cottolengo
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
General criteria: * Female participants aged 18 years or older. * Histologically confirmed invasive breast carcinoma diagnosed by core needle biopsy. * Unifocal and unilateral tumor. * Tumor clearly visible and accessible by ultrasound. * Tumor considered technically suitable for ultrasound-guided cryoablation, with the possibility of achieving adequate ice-ball coverage and safety margins. * No known distant metastatic disease. * Ability to understand the study procedures and provide written informed consent. Cohort A: \- Participants considered unsuitable for breast surgery because of age, comorbidities, or other clinical conditions, or participants who decline surgical treatment after appropriate multidisciplinary evaluation. Cohort B: * Postmenopausal participants with early-stage, low-risk invasive breast cancer. * Invasive tumor preferably 15 mm or smaller. * Hormone receptor-positive (estrogen receptor and/or progesterone receptor positive). * HER2-negative. * Histological grade 1 or 2. * Clinically node-negative disease. * Invasive carcinoma of no special type or another favorable low-risk histological subtype
Exclusion criteria
* Multifocal or multicentric breast cancer. * Bilateral breast cancer requiring treatment. * Tumor not adequately visible or accessible by ultrasound. * Tumor location or anatomy preventing safe cryoablation or achievement of an adequate ablation margin. * Known distant metastatic disease. * HER2-positive invasive breast cancer for Cohort B. * Predominantly extensive intraductal disease or other findings considered unsuitable for cryoablation. * Contraindication to the planned cryoablation procedure. * Inability to provide informed consent or comply with study follow-up.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Tumor Ablation at 6 Months | 6 months after cryoablation | Proportion of participants with complete local tumor ablation at approximately 6 months after cryoablation. Complete ablation will be assessed by clinical examination, breast ultrasound, and contrast-enhanced mammography (CEM), with no evidence of residual viable tumor. Histologic confirmation by percutaneous biopsy will be performed only when clinical or imaging findings are suspicious or inconclusive. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Technical Success of Cryoablation | During the cryoablation procedure | Proportion of cryoablation procedures successfully completed according to the planned protocol, with adequate positioning of the cryoprobe and complete coverage of the target tumor by the ice ball, including the planned safety margin, as assessed by real-time ultrasound monitoring. |
| Procedure-Related Adverse Events | From the cryoablation procedure through 30 days after treatment | Incidence and severity of adverse events related to the cryoablation procedure, including pain, bleeding, hematoma, infection, skin injury, and other procedure-related complications. |
| Residual or Recurrent Local Disease | Up to 24 months after cryoablation | Proportion of participants with imaging findings suggestive of residual or recurrent tumor at the treated site during follow-up. Assessment will be based on clinical examination, ultrasound, and contrast-enhanced mammography. Biopsy will be performed when imaging or clinical findings are suspicious or inconclusive. |
| Additional Local Treatment | Up to 24 months after cryoablation | Proportion of participants requiring additional local treatment of the treated breast tumor because of suspected or confirmed residual or recurrent disease, including repeat cryoablation or surgical treatment. |
| Cryoablation Procedure Duration | During the cryoablation procedure | Duration of the cryoablation procedure, measured from the start of cryoprobe placement to completion of cryoprobe removal. |
| Ablation Margin | During the cryoablation procedure | Minimum distance between the tumor boundary and the outer margin of the ice ball during cryoablation, as measured by real-time ultrasound. The measurement will be recorded in millimeters. |
Countries
Italy
Contacts
CONTACTEUGENIO ZANON, MD
PRINCIPAL_INVESTIGATOREUGENIO ZANON, MD
Ospedale Cottolengo - Breast Unit
Outcome results
None listed