Breast Tissue ablation by Conductive Heating

描述（由申请人提供）：乳腺癌影响1/7的妇女在其一生中，这意味着13%的终身患病概率。每年有近220，000例新病例被诊断为乳腺癌;在这些病例中，75%的病例处于早期阶段（I或II）。在这些早期阶段，乳腺癌患者可以通过保乳手术（BCS）进行治疗。在初次手术后，高达40%的病例由于手术切缘不足而导致局部复发，在肿瘤切除部位留下了活的癌细胞（即阳性切缘）。我们建议使用一种新型器械，通过传导性热消融，在术中对乳房肿瘤切除术后的空腔进行可靠和精确的灭菌，创建一个无肿瘤的空腔，以降低BCS中因切缘不足而导致的40%复发率。我们已经设计、构建并测试了一种能够在体内实现高效传导热消融的器械，如本提案的初步研究所示。基于这些结果，我们假设传导性间质热疗（CITT）可以可靠和精确地在靶组织中诱导不可逆的热损伤，以在原发性肿瘤切除后对手术切缘进行“消毒”。我们的最终目标是我们的设备将成为BCS的术中治疗，以减少由于手术切缘不足而导致的局部肿瘤复发。在本项目中，我们的目标是证明CITT在创建阴性切缘方面的控制性和可预测性以及CITT切缘消融的临床前有效性。为了实现这一目标，我们将努力实现以下具体目标。具体目标1。证明我们有能力在猪模型体内控制CITT引起的热损伤程度。具体目标2。证明CITT可以在体内可靠地创建阴性边界。我们的长期目标是开发一种新的治疗模式，通过将恶性肿瘤的手术切除与CITT的有效、可预测的边缘热消融相结合，实现乳腺癌的当天诊断和一线治疗;重要的是，这种方式对患者和手术团队都是安全的。通过进一步的研究，它也可以应用于其他类型的癌症（例如肺癌，肾癌，头颈部），这些癌症涉及实体瘤的手术切除。

DESCRIPTION (provided by applicant): Breast cancer affects 1 in 7 women during their lifetime, which translates to a 13% lifetime probability of developing the disease. Nearly 220,000 new cases are diagnosed with breast cancer each year; in 75% of these cases, the disease is at early stage (I or II). At these early stages, breast cancer patients can be treated via breast conservation surgery (BCS). Following the initial surgery, up to 40% of the cases result in local recurrence due to inadequate surgical margins with viable cancer cells left at the lumpectomy site (i.e. positive margins). We propose to reduce the 40% recurrence rates caused by inadequate margins in BCS using a novel device that reliably and precisely sterilizes the post-lumpectomy cavity, creating a tumor-free cavity, intraoperatively, via conductive thermal ablation. We have designed, built, and tested a device that enables highly effective conductive thermal ablation in vivo, as shown in the Preliminary Studies of this proposal. Based on these results, we hypothesize that conductive interstitial thermal therapy (CITT) can reliably and precisely induce irreversible thermal damage in targeted tissue to "sterilize" surgical margins after primary tumor resection. Our ultimate goal is that our device will become an intraoperative treatment in BCS to reduce local tumor recurrence resulting from inadequate surgical margins. In this project, our objective is to demonstrate the control and predictability of CITT in creating negative margins and the preclinical efficacy of margin ablation by CITT. To achieve this objective, we will pursue the following specific aims. Specific Aim 1. Demonstrate our ability to control the extent of thermal damage resulting from CITT, in vivo, in a swine model. Specific Aim 2. Demonstrate that CITT can reliably create negative margins, in vivo. Our long-term goal is to develop a new treatment paradigm for same-day diagnosis and first-line treatment of breast cancer by combining surgical resection of malignant tumors with effective, predictable thermal ablation of the margins by CITT; importantly, this modality is safe for both the patient and the surgical team. It can also be applied, through further research, to other types of cancers (e.g. lung, kidney, head and neck) that involve surgical resection of solid tumors.