The Treatment of Breast Cancer with Percutaneous Thermal Ablation: A phase 2 screening trial

Introduction
Breast cancer is the most common type of cancer among women worldwide. Almost half of the tumors are ≤ 2cm. These patients have an excellent prognosis with current surgical therapy (5-year survival rate of 98-99%). Percutaneous thermal ablation has the potential to replace surgical treatment and improve the health-related quality of life of these patients. Especially RFA, MWA and cryoablation are promising techniques as an alternative to surgical resection without jeopardizing current treatment effectiveness or safety. Success rates of RFA, MWA and cryoablation are 82-87%, 83-90% and 74-75%, respectively. Due to great heterogeneity between studies and a large variation in complete ablation rates, a formal recommendation on the best technique for a phase 3 study is not possible based on current literature. Additionally, to little is known about patient satisfaction and cosmetic outcome, immune response after thermal ablation, follow-up imaging, long-term benefits and complications.
Therefore, the objective of this study is to determine the efficacy rate in terms of complete ablation for the most promising techniques of thermal ablation (RFA, MWA or CA) for patients with early stage breast cancer to warrant a randomized phase III trial comparing thermal ablation with surgery.

Methods
This is an open-label randomized phase 2 screening trial. Postmenopausal women diagnosed with unilateral invasive cT1N0M0 breast cancer with a DCIS component ≤ 25% of the total tumor will be included. A total of 63 patients will be randomized to radiofrequency ablation (n = 21), microwave ablation (n = 21) or cryoablation (n = 21). To evaluate whether the tumor was completely ablated, surgical resection will be performed 3 months after thermal ablation. The primary endpoint is the percentage of tumours with complete ablation at pathologic evaluation with CK8/18 and H&E staining. Secondary endpoints are: feasibility in an outpatient setting, degree of immune response, adverse events, patient satisfaction, cosmetic outcome and the predictive value of MRI.

We hypothesize that success rates in terms of complete ablation rate will be comparable across the techniques and that only minor complications will occur in ≤10% of all patients. We mainly expect differences in patient satisfaction because of differences in treatment time and temperature.

MRI before thermal ablation, 2 weeks after thermal ablation and before surgical resection
Cosmetic outcome questionnaire (Breast-Q and BCTOS-13), before thermal ablation, before surgical resection, two weeks after surgical resection, one year after surgical resection, 4 years after surgical resection
Cosmetic outcome photographs (BCCT.core), before thermal ablation, before surgical resection, two weeks after surgical resection, one year after surgical resection, 4 years after surgical resection
Blood withdrawal, 2 weeks after thermal ablation, before surgical resection, and two weeks after surgical resection
Thermal ablation procedure within 2 weeks after inclusion

Cryoablation (CA), Radiofrequency ablation (RFA) and Microwave ablation (MWA)