Abstract OT3-07-01: Efficacy of magnetic resonance-guided high intensity focused ultrasound for the ablation of breast cancer
Authors: de Maar Josanne Sophia , Deckers Roel , Bartels Lambertus Wilhelmus , van Dalen Thijs , van Gorp Joost , van Diest Paul J , Witkamp Arjen J , Vaessen H. H.B. , Braat Maria NicoleGerardineJohanna Aleida , Moonen Chrit 
Published: March 2020

Abstract
Background: Over the past decades, breast cancer treatment has evolved from extensive disfiguring surgery to less invasive procedures. In patients with small localized tumors breast conserving therapy (BCT) has become the standard of care. However, surgery still involves risks associated with general anesthesia and complications such as bleeding, infection and suboptimal cosmetic results. Conversely, Magnetic Resonance-guided High intensity Focused Ultrasound (MR-HIFU) ablation of breast cancer is an entirely non-invasive procedure that can be performed under procedural sedation and analgesia (PSA). With MR-HIFU, a focused ultrasound beam penetrates through soft tissues and causes localized heating (55-70°C) of a target. Magnetic resonance imaging (MRI) is used for target-identification and real-time temperature-monitoring (MR thermometry). In a previous phase I study in ten breast cancer patients, tumors were deliberately partially ablated and safety and accuracy of a dedicated MR-HIFU breast system (Profound Medical) was shown.1,2 This system’s lateral sonication approach and wide aperture reduce the risk of heating heart, lungs and skin to a minimum.3 In the current study we aim to demonstrate that complete breast tumor ablation with MR-HIFU is feasible.
Trial design: Single-arm phase II study in patients with primary breast cancer. We will use a dedicated MR-HIFU breast system (Profound Medical) to ablate breast tumors before BCT or mastectomy, in a treat-and-resect protocol. We will perform MRI before MR-HIFU, during the MR HIFU session and one week after to evaluate radiologic response. Primary endpoint is efficacy, assessed by percentages of necrotic and residual viable tumor. Secondary endpoint is safety, assessed by adverse events and cosmetic changes. Descriptive statistics will be used.
Eligibility criteria Non-pregnant, non-lactating women ≥18 years of age, weighing &lt; 90 kg, who have:
histologically proven invasive breast cancer, cT1-2 N0-2 Mx, subtypes invasive ductal carcinoma or invasive carcinoma ‘not otherwise specified’ / ‘no special type’ a tumor in reach of the HIFU beams, diameter ≤ 3.0 cm and distance ≥1.5 cm to skin, nipple and pectoral wall WHO-Performance Score ≤2 a body size fitting in the MR bore and the ability to lie in prone position
no prior treatment with neoadjuvant chemotherapy in the past 3 months
no prior radiotherapy, thermal therapy or surgery in the targeted breast
no contraindications to PSA, MRI or MRI contrast agents
no conditions that may interfere with MR-HIFU such as a pacemaker, scar tissue, breast prosthesis or surgical clips
no extensive intraductal components, determined on biopsy
Additionally, patients may be excluded when the risk of adjuvant over- or undertreatment (due to performing Bloom and Richardson grading on the tumor biopsy) is considered too high.
Target accrual 10 patients (present: 0, IRB approval obtained)
Conclusion In this phase II trial we aim to show the feasibility of complete tumor ablation of breast cancer with a dedicated MR-HIFU breast system. This approach could lead to a non-invasive treatment alternative for selected patients with primary breast cancer.
References 1Merckel 2016, Eur Radiol; 2Deckers 2015, Phys Med Biol; 3Merckel 2013, Cardiovasc Intervent
Radiol;
Acknowledgements Financial support of Center for Translational Molecular Medicine and Vrienden UMC Utrecht. Profound Medical provides non-financial support.
Contact information Josanne de Maar, j.s.demaar@umcutrecht.nl ClinicalTrials.gov Identifier: NCT02407613
Citation Format: Josanne Sophia de Maar, Roel Deckers, Lambertus Wilhelmus Bartels, Thijs van Dalen, Joost van Gorp, Paul J van Diest, Arjen J Witkamp, H. H.B. Vaessen, Maria NicoleGerardineJohanna Aleida Braat, Chrit Moonen. Efficacy of magnetic resonance-guided high intensity focused ultrasound for the ablation of breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT3-07-01.