Early Breast Cancer Ultrasound-guided Visual-ICE Galil Cryoablation; Can Tumor Cell Death Induced by Cryoablation be Detected by Specific Circulating Markers?
Trial ID: NCT05727813
Status: COMPLETED
Study type: INTERVENTIONAL
Phase: NA
Start date: 2022-09-01
Completion date: 2023-01-27
Sponsor: University of Roma La Sapienza
Conditions: Cancer, Treatment-Related; Tumor of Breast; Systemic Inflammatory Response; Stage I Breast Cancer
Interventions: cryoablation
Locations: Sapienza University of Rome
Countries: Italy
Enrollment: 20
Age range: 18 Years - None
Sex: FEMALE

Summary:
The aim of our study is to examine the cryoimmunologic response and its mechanisms induced by US-guided cryoablation of small breast tumors (\<2 cm) not eligible to neoadjuvant therapy. We will recruit 30 women who will undergo cryoablation and their results will be compared with a control group of 30 women, who will follow the same therapeutic pathway without performing cryoablation. All recruited patients will undergo an enrollment check, pre-cryoablation breast MRI and blood test to assess immune response, breast cancer US-guided cryoablation, post-cryoablation breast MRI and the same blood test to evaluate immunologic response. Within 21 days all patients will undergo breast surgery, with immuno-histopathological analysis on surgical specimen.

At least 10 days after surgery the patient will undergo clinical breast examination, blood test to assess immune response and patient satisfaction questionnaire.

Cryoablation treatment will be performed using a 14G cryoprobe under us-guidance for visualization of the ice ball surrounding the lesion. The ultrasound guide is used to ensure that the action affects the entire tumor and that therapeutic temperatures are reached in every part of the tumor.

Pre- and post- cryoablation breast MRI will be performed on a 3T magnet to assess cryoablation rate of success. Artificial intelligence algorithms will also be used for this purpose. Cryoablation treatment efficacy will also be evaluated with ultrasound.

The immunological fitness of cancer patients will be studied by flow cytometry, evaluating the presence of cytokines/chemokines relevant during anticancer immune response/tumor progression and for the presence of molecules released by cells during an immunogenic cell death.

The goal of our study will be to demonstrate that cryoablation of breast cancer can induce an antitumor immune response.

Therefore this approach could become an additional tool in the oncological treatment of breast cancer.

Eligibility criteria:
Inclusion Criteria:

* ≥ 18 year-old women with needle (14-20 G) biopsy-proven invasive breast cancer. The specimens taken are adequate for tumor classification and receptors analysis;
* imaging (ultrasound and magnetic resonance imaging) confirmed single \<2 cm breast cancer;
* clearly visible lesion on ultrasound with a minimum distance of 1 cm between the tumor and the skin and 2 cm between the tumor and the nipple;
* not eligible patients for neo-adjuvant therapy;
* patients who are scheduled for breast cancer surgical resection (lumpectomy or mastectomy) after cryoablation; stage I disease: T1 N0;

Exclusion Criteria:

* DCIS without invasive components on the core biopsy;
* Tamoxifen, aromatase inhibitors and neoadjuvant chemotherapy within 30 days prior to Visual-ICE treatment;
* XRT or previous ablative therapy to the affected breast;
* distance \<1 cm between the tumor and the skin, the nipple or the chest wall;
* microcalcifications as the only evidence of breast cancer on imaging;
* breast implants;
* severe cardiac or cerebrovascular disease;
* pregnancy, nursing or puerperium;
* patients with a general health status ASA\> 2, which includes in a non-limiting way patients suffering from renal dysfunction due to hepatorenal syndrome or who are in the perioperative period for liver transplantation;
* active and ongoing infection, e.g. urinary tract infection, respiratory tract infection and other known infections;
* poor blood glucose control;
* severe hypertension;
* any contraindications for Visual-ICE ablation therapy;
* sleep apnea syndrome

Outcomes:
Immunogenic Cell Death induced by tumor cryoablation, cytokines; Immunogenic Cell Death induced by tumor cryoablation, pro-inflammatory cytokines; Immunogenic Cell Death induced by tumor cryoablation, immunosuppressive cytokines; Immunogenic Cell Death induced by tumor cryoablation, chemokines; Immunogenic Cell Death induced by tumor cryoablation, ATP and HMGB1