A Cohort Study of Combined Cryoablation and Thermal Ablation for Non-surgical Treatment of Breast Cancer Patients

Peking University People's Hospital Breast Surgery Department

Although surgical resection is the gold standard for early breast cancer treatment, some patients cannot tolerate surgery due to medical conditions or refuse surgical treatment for cosmetic reasons. In recent years, the rapid development of ablation technology has provided new directions for breast cancer patients who are not suitable for surgical treatment. Ablation uses high or low temperatures to deactivate lesions or tissues, which are gradually absorbed by the body, achieving local treatment purposes. Its safety and efficacy have been preliminarily confirmed. As an advanced minimally invasive medical device independently developed in China, the combined cryo-thermal ablation system treats tumors using a combined mode of deep cryogenic freezing and high-intensity heating. It has been approved for ablation treatment of various solid tumors including lung cancer, pancreatic cancer, kidney cancer, prostate cancer, breast cancer, bone and soft tissue sarcomas.

This project proposes a prospective cohort design, based on the breast disease cohort database of Peking University People's Hospital Breast Center. It will enroll patients pathologically diagnosed with breast cancer, determined unsuitable for surgical treatment, and have received combined cryo-thermal ablation. The registered data will be used to evaluate the effectiveness and safety of percutaneous ultrasound-guided cryo-thermal composite ablation in this population.

1. Study Design

1. Prospective Cohort Study Study Subjects and Selection Criteria
2. This study is based on the breast disease cohort database of Peking University People's Hospital Breast Center. Patients with pathologically confirmed breast cancer who refused, were intolerant of, or unsuitable for surgical treatment and received combined cryoablation and thermal ablation were prospectively enrolled.

The specific inclusion and exclusion criteria are as follows:

1. Inclusion Criteria (all conditions must be met):

   ≥18 years old; Breast cancer confirmed by core needle biopsy; Tumor lesions clearly visible on ultrasound; No contraindications for cryoablation such as coagulation disorders;

   Presence of reasons unsuitable for conventional surgical resection:

   Patients intolerant to general anesthesia or surgical treatment due to medical conditions; Due to unresectable and/or metastatic disease; Patient refusal of surgery, etc.; Agree to undergo ablation surgery and sign the informed consent form.

2. Exclusion Criteria (Participants will be excluded if any of the following apply):

Missing clinical and pathological data (such as imaging or pathological materials); Pregnant or lactating women; Known allergies, intolerance, or contraindications to cryotherapy (such as cryoglobulinemia, presence of implanted electronic devices); Vulnerable populations, including those with neurological disorders, cognitive impairments, critically ill patients, etc.

3)Grouping of Study Subjects This study is a prospective cohort study. The decision to undergo combined cold and heat ablation therapy was made through mutual consultation between patients and attending physicians, while the remaining systemic treatments were not affected by the study.Cohort 1: Ablation therapy for patients who cannot tolerate standard surgery due to advanced age or comorbidities;Cohort 2: Ablation therapy for patients with unresectable/metastatic diseases who are not suitable for surgical resection;Cohort 3: Ablation therapy chosen by patients who refuse surgical treatment for personal reasons.

4)Research Steps Screen patients who meet the inclusion criteria and exclude those who meet the exclusion criteria.

Collect patients' clinicopathological data: age, menstrual status, accompanying diseases; tumor imaging information, including ultrasound, mammography, MRI reports, tumor size, and axillary lymph node status; pathological information, including pathological type, histological grade, hormone receptor status, and postoperative adjuvant treatment plans.

Breast primary tumors receive standard combined cryoablation and thermal ablation treatment, and collect imaging and histological laboratory data during and after treatment.

Retrieve patients' prognosis information from the follow-up database, including recurrence, metastasis, second primary tumor, and mortality events.

5)Follow-up Plan and Contents:

Postoperative Complications (within 3 months):

Skin damage Poor incision healing Infection Seroma formation Nipple or flap ischemia/necrosis

Survival-related Follow-up:

Recurrence Metastasis Second primary tumor Mortality events

Follow-up Methods:

Telephone WeChat client of Peking University People's Hospital Follow-up System Follow-up Interval: 6 months Follow-up Duration: More than 5 years 6)Selection and Confirmation of Primary Measurement Indicators or Outcome Measures

Primary Study Endpoint - Safety:

Intraoperative complications (e.g., bleeding, vascular/nerve injury) Postoperative complications (infection, hematoma, frostbite, breast deformity, paresthesia, etc.), recorded according to CTCAE v5.0 classification Local tumor recurrence rate (Ipsilateral Breast Cancer Recurrence, IBTR): defined as the time from surgery to ipsilateral breast tumor recurrence, with the occurrence of ipsilateral breast tumor recurrence as the event

Secondary Study Endpoints:

Disease-free survival (DFS): time from study enrollment to the first occurrence of failure events, including ipsilateral local-regional recurrence, contralateral breast cancer, distant recurrence, or death from any cause Overall survival (OS): time from study enrollment to death from any cause Exploratory analysis: using specimen bank preserved samples and imaging data to analyze post-ablation tumor tissue pathological response, blood immune function assessment, and the correlation between postoperative imaging (MRI/ultrasound) characteristics and recurrence risk All data collection is sourced from the established Peking University People's Hospital Breast Disease Cohort Database (PKUPH Breast Disease Cohort).

7)The primary study outcome was a local IBTR at 5 years through the width of the 95% confidence interval (CI). A sample size was calculated for this outcome. For a two-sided 95% exact Clopper Pearson confidence interval of the IBTR rate whose true value was 5%, a sample size of 200 patients was required to yield a half-width of 5% at most with more than 99% power. In this context, power is the probability (conditional method) of obtaining a confidence interval a half-width less than or equal to the hypothesized value.

Inclusion Criteria:

• 1) Aged 18 or above; 2) Breast cancer confirmed by core needle biopsy; 3) Tumor lesions clearly visible on ultrasound; 4) No contraindications for cryoablation such as coagulation disorders; 5) Presence of reasons unsuitable for conventional surgical resection: patient's condition cannot tolerate general anesthesia or surgical treatment; due to unresectable and/or metastatic disease; patient refuses surgery, etc.; 6) Agree to undergo ablation surgery and sign the consent form.

Exclusion Criteria:

• 1) Missing clinical and pathological data (such as imaging and pathological materials); 2) Pregnant or lactating women; 3) Known allergies, intolerances, or contraindications to cryotherapy (such as cryoglobulinemia, presence of implanted electronic devices); 4) Vulnerable populations, including those with neurological disorders, cognitive impairments, critically ill patients, etc.