The development of advanced imaging and dosimetry for permanent breast seed implant radiation therapy

据估计，到2020年，将有2.7万名加拿大女性被诊断出患有乳腺癌。这种治疗，手术之后是3.5到7周的每日放射治疗（RT），给我们的医疗保健系统和患者带来了巨大的负担。事实上，偏远社区的患者可能由于在远离家乡的地方接受治疗所面临的挑战而无法完成他们的RT。永久乳房种子植入（PBSI）是一种新型、有效的乳房RT，可在一天内完成，从而显著减轻医疗负担。我的研究项目集中在开发新的成像和剂量测量工具和技术，以帮助实现PBSI在加拿大。PBSI是通过在二维超声（2DUS）成像引导下将放射性种子植入乳房来实施的。虽然有效，但PBSI在技术上具有挑战性，我的研究小组率先开发了技术和剂量分析工具，以提高PBSI的精度和稳健性。我们是第一个量化植入物交付的不确定性，并发现美国清晰度影响植入物的准确性。我们已经开发了准确记录术后皮肤剂量（治疗毒性风险）和靶剂量的方法。我们与Robarts Imaging合作开发了一种用于PBSI的非临床原型3DUS扫描仪。在此，我们建立在这项工作的基础上，以解决PBSI成像、精度、个体化靶向和植入后定量剂量测定的主要瓶颈。本提案的目标是：目标1：基于3DUS的PBSI：长期：开发完全基于3DUS的PBSI技术。5年：开发和验证3DUS技术用于PBSI靶标描绘和植入物引导，从而提高现有方案的治疗准确性。目标2：个性化目标：长期：开发个性化，精准，PBSI的方法。5年：模拟植入物交付的不确定性，建立PBSI靶向的个体化边界，从而实现PBSI治疗的高精度、个体化靶向。目标3：准确的植入后剂量测定：长期：开发定量剂量测定系统，用于准确的剂量-结果分析。5年：建立种子移动、皮肤划定和乳房屏蔽对皮肤剂量的剂量学影响模型，并通过实验确定乳房位置对治疗剂量的影响。结果将提高植入后剂量分析的准确性，超过目前的方法。这项工作将建立一个技术框架，以实现精确的、图像引导的、个性化的、自适应的PBSI，并最终支持我的长期研究目标，确保加拿大各地的乳腺癌单日放射治疗的可用性。我的工作也将对加拿大的未来产生积极影响，培养5名HQP成为学术界、医院或工业界的医学物理学领袖。作为年轻女性的导师，我的HQP培训将有助于解决我们这个领域的性别失衡问题。

An estimated 27,000 Canadian women will be diagnosed with breast cancer in 2020. The treatment, surgery followed by 3.5 to 7 weeks of daily radiation therapy (RT), presents a significant burden to both our health care system and our patients. In fact, patients in remote communities may not complete their RT due to challenges in undertaking treatment far from home. Permanent breast seed implant (PBSI) is a novel, effective, breast RT that is undertaken in a single day, thereby significantly reducing the healthcare burden. My research program is focused on developing novel imaging and dosimetry tools and techniques to help enable PBSI across Canada. PBSI is administered by implanting radioactive seeds into the breast under two-dimensional ultrasound (2DUS) imaging guidance. While effective, PBSI is technically challenging and my research group has pioneered the development of technology and dose analysis tools to increase the precision and robustness of PBSI. We were the first to quantify the uncertainty in implant delivery and to discover that US clarity impacts implant accuracy. We have developed methodologies for accurately recording skin dose (a risk for treatment toxicity) and target doses post-operatively. In collaboration with Robarts Imaging we have developed a non-clinical prototype 3DUS scanner for PBSI. Here we build on this work to address primary bottlenecks in PBSI imaging, precision, individualized targeting, and quantitative post-implant dosimetry. The aims of this proposal are: Aim 1: 3DUS based PBSI: Long-term: To develop a fully 3DUS-based PBSI technique. Five-year: To develop and verify 3DUS technology for PBSI target delineation and implant guidance, thereby enabling improved treatment accuracy over existing protocols. Aim 2: Individualized targeting: Long-term: To develop methodology for personalized, precision, PBSI. Five-year: To model uncertainties in implant delivery and establish individualized margins for PBSI targeting, thereby enabling high precision, individualized targeting of PBSI treatments. Aim 3: Accurate post-implant dosimetry: Long-term: To develop quantitative dosimetry systems for accurate dose-outcome analysis. Five-year: To model the dosimetric impacts of seed movement, skin delineation, and breast shielding on skin dose, and to experimentally determine the impact of breast position on treatment dose. The result will be improved accuracy of post-implant dose analysis over current methodologies.  This work will establish a technical framework to enable precise, image-guided, individualized, adaptive PBSI and ultimately support my long-term research goal to ensure the availability of single day breast cancer radiation treatment across Canada. My work will also positively impact Canada's future by training a diverse group of 5 HQP to be medical physics leaders in academia, hospitals, or industry. As a mentor for young women, my HQP training will help address the gender imbalance in our field.