Breast Tissue ablation by Conductive Heating

描述（由申请人提供）：每7名妇女中就有1人患乳腺癌，这意味着一生中患乳腺癌的概率为13%。每年有近22万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期）。在这些早期阶段，乳腺癌患者可以通过乳房保护手术（BCS）进行治疗。初次手术后，高达40%的病例由于手术切缘不充分导致局部复发，在乳房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颖的装置，通过传导热消融，可靠而精确地对乳房肿瘤切除术后的腔体进行消毒，以减少40%的BCS边缘不足引起的复发率。我们已经设计、制造并测试了一种能够在体内高效导电热消融的装置，如本提案的初步研究所示。基于这些结果，我们假设传导间质热疗法（传导间质热疗法，传导间质热疗法）可以可靠而精确地诱导目标组织的不可逆热损伤，以“消毒”原发肿瘤切除后的手术边缘。我们的最终目标是使我们的设备成为BCS的术中治疗手段，以减少由于手术切缘不足而导致的局部肿瘤复发。在这个项目中，我们的目标是证明CITT在产生负切缘方面的控制和可预测性，以及CITT切缘消融的临床前疗效。为实现这一目标，我们将努力实现以下具体目标：具体目标证明我们的能力，以控制热损伤的程度造成的CITT，在体内，在猪模型。具体目标2。在体内证明CITT可以可靠地产生负边际。我们的长期目标是开发一种新的治疗模式，通过将恶性肿瘤手术切除与有效、可预测的CITT边缘热消融相结合，实现乳腺癌的当日诊断和一线治疗；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，它也可以应用于需要手术切除实体瘤的其他类型的癌症（如肺癌、肾癌、头颈癌）。

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.