Early Breast Cancer Ultrasound-guided Visual-ICE Galil Cryoablation; Can Tumor Cell Death Induced by Cryoablation be Detected by Specific Circulating Markers?
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Immunogenic Cell Death induced by tumor cryoablation, cytokines
研究概览
简要总结
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.
详细描述
We will enroll women with a biopsy-proven diagnosis of early-stage breast cancer (T1 N0), not eligible for neo-adjuvant therapy, scheduled to breast surgery (mastectomy or nodulectomy), who have given informed consent for the study.
We will recruit 30 women who will undergo cryoablation. Their results will be compared with those obtained from a control group of 30 women, who will follow the same therapeutic pathway for the treatment of breast cancer without performing cryoablation.
The primary objective of our study is the characterization of the Immunogenic Cell Death (ICD) induced, the inflammatory response and the modulation of circulating T immune cells induced by tumor cryoablation treatment in the serum of breast cancer patients.
The circulating ICD biomarkers HMGB1, calreticulin and HSP70/90 will be analysed and also the profile of Th1 and Th2 type cytokines (IFN-γ, IL-12 (p40/p70), IL-15, IL-17, IL-2, IL-7, IP-10, IL-13, IL-5, IL-4), pro-inflammatory cytokines (IL-1α, IL-1β, IL- 6, TNF-α, IL-1RA, IL-2R, IL-8, CRP, IL-17, IFN-α), immunosuppressive cytokines (TGF-β1, IL-10, PGE2), chemokines (CCL5/RANTES, CCL3/MIP-1α, CCL4/MIP-1β, CCL2/MCP-1, CXCL9/MIG, CCL11/Eotaxin). Immune cell subsets will be characterized by flow cytometry: besides the conventional immune cell subsets (NK, Monocyte, Granulocyte, T and B cells), specific T cell subsets (Treg, naïve, memory, central effector) will be characterized and also the expression of immune markers associated to activation (CD137) or suppression/exhaustion (PD1, CTLA4, TIM3, LAG3).
Secondary endpoints are:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •≥ 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;
排除标准
- •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
结局指标
主要结局
Immunogenic Cell Death induced by tumor cryoablation, cytokines
时间窗: 12 months
Characterization of the Immunogenic Cell Death induced by tumor cryoablation treatment in the serum of breast cancer patients. Evaluation of serum modifications of the following molecules: Th1 and Th2 type cytokines (IFN-γ, IL-12 (p40/p70), IL-15, IL-17, IL-2, IL-7, IP-10, IL-13, IL-5, IL-4)
Immunogenic Cell Death induced by tumor cryoablation, pro-inflammatory cytokines
时间窗: 12 months
Characterization of the Immunogenic Cell Death induced by tumor cryoablation treatment in the serum of breast cancer patients. Evaluation of serum modifications of the following molecules: pro-inflammatory cytokines (IL-1α, IL-1β, IL-6, TNF-α, IL-1RA, IL-2R, IL-8, CRP, IL-17, IFN-α),
Immunogenic Cell Death induced by tumor cryoablation, immunosuppressive cytokines
时间窗: 12 months
Characterization of the Immunogenic Cell Death induced by tumor cryoablation treatment in the serum of breast cancer patients. Evaluation of serum modifications of the following molecules: immunosuppressive cytokines (TGF-β1, IL-10, PGE2),
Immunogenic Cell Death induced by tumor cryoablation, chemokines
时间窗: 12 months
Characterization of the Immunogenic Cell Death induced by tumor cryoablation treatment in the serum of breast cancer patients. Evaluation of serum modifications of the following molecules: chemokines (CCL5/RANTES, CCL3/MIP-1α, CCL4/MIP-1β, CCL2/MCP-1, CXCL9/MIG, CCL11/Eotaxin),
Immunogenic Cell Death induced by tumor cryoablation, ATP and HMGB1
时间窗: 12 months
Characterization of the Immunogenic Cell Death induced by tumor cryoablation treatment in the serum of breast cancer patients. Evaluation of serum modifications of the following molecules: ATP and HMGB1 are molecules released in the serum by cancer cells during immunogenic cell death.
次要结局
- safety margin of Cryoablation treatment(12 months)
- Rate of complete response(12 months)
- Cryoablation treatment capability to induce immunogenic tumor cell death, specimen(12 months)
研究者
federica pediconi
Prof. Federica Pediconi
University of Roma La Sapienza