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

据估计，2020年将有27，000名加拿大妇女被诊断患有乳腺癌。治疗，手术后3.5至7周的每日放射治疗（RT），提出了一个显着的负担，我们的医疗保健系统和我们的病人。事实上，偏远社区的患者可能无法完成RT，因为在远离家乡的地方进行治疗存在挑战。永久性乳房粒子植入体（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。我的研究项目主要集中在开发新的成像和剂量测定工具和技术，以帮助在加拿大实现PBSI。PBSI是通过在二维超声（2DUS）成像引导下将放射性粒子植入乳房来进行的。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输送的不确定性并发现US清晰度影响植入物准确性的公司。我们已经开发了用于准确记录皮肤剂量（治疗毒性风险）和术后目标剂量的方法。与Robarts Imaging合作，我们开发了一种用于PBSI的非临床原型3DUS扫描仪。在这里，我们建立在这项工作，以解决PBSI成像，精度，个性化的目标，和定量植入后剂量测定的主要瓶颈。 该提案的目标是：目标1：基于3DUS的PBSI：长期：开发完全基于3DUS的PBSI技术。五年：开发并验证用于PBSI靶点勾画和植入引导的3DUS技术，从而提高现有方案的治疗准确性。 目标2：个性化目标：长期：制定个性化、精确的PBSI方法。五年：对植入物输送的不确定性进行建模，并建立PBSI靶向的个体化范围，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。五年：模拟放射性粒子移动、皮肤描绘和乳房屏蔽对皮肤剂量的剂量影响，并通过实验确定乳房位置对治疗剂量的影响。其结果将是提高准确性的植入后剂量分析超过目前的方法。 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，以确保加拿大各地的乳腺癌单日放射治疗的可用性。我的工作也将积极影响加拿大的未来，通过培训一个多元化的5个HQP小组成为学术界，医院或工业界的医学物理学领导者。作为年轻女性的导师，我的HQP培训将有助于解决我们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.