Evaluation of image-guided, conformal, high-dose intraoperative radiation therapy (Precision Breast IORT) for early stage breast cancer

图像引导、适形、高剂量术中放疗（精准乳腺 IORT）对早期乳腺癌的评估

• 批准号: 10463616
• 负责人: Shayna Lefrak Showalter
• 金额: $ 37.76万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-20 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10463616
• 关键词: Address; Adjuvant; Aftercare; Appearance; Blood specimen; Brachytherapy; Breast; Breast-Conserving Surgery; Catheters; Cells; Clinical; Communities; Cosmetics; Custom; Data; Dose; Early treatment; Exposure to; Foundations; Fractionation; Future; Health Care Costs; Heart; High-Dose Rate Brachytherapy; Image; Image Analysis; Image-Guided Surgery; Immune; Immune response; Immune system; Immunization; Immunologics; Immunosuppression; Immunotherapy; Impairment; Institution; Intraoperative Radiation Therapy; Ipsilateral; Lead; Low Dose Radiation; Lymphocyte Count; Lymphocyte Function; Lymphopenia; Malignant Neoplasms; Mammary Gland Parenchyma; Mammary Neoplasms; Medical; Methods; Normal tissue morphology; Outcome; Patient Preferences; Patient-Focused Outcomes; Patients; Phase; Phase II Clinical Trials; Photons; Physicians; Policies; Population; Publishing; Quality of life; Quality-Adjusted Life Years; Radiation; Radiation Dose Unit; Radiation Oncologist; Radiation exposure; Radiation therapy; Recurrence; Reporting; Research; Risk; Scanning; Shapes; Site; Skin; Specific qualifier value; Surgeon; Techniques; Testing; Time; Uncertainty; Variant; X-Ray Computed Tomography; alternative treatment; arm; base; breast lumpectomy; cancer recurrence; cohort; comparative effectiveness; comparative effectiveness study; cost; cost effectiveness; cytokine; dosimetry; efficacy evaluation; feasibility trial; health care availability; high risk; image guided; immune function; improved; insight; irradiation; malignant breast neoplasm; markov model; novel; peripheral blood; phase 1 study; phase II trial; preservation; prospective; radiation delivery; radiation effect; radiological imaging; response; safety and feasibility; targeted imaging; three dimensional treatment planning; time use; treatment planning; trial design; tumor

Our proposal aims to improve the efficacy of intraoperative radiation therapy (IORT) for the treatment of early stage breast cancer, to investigate the immune effects of breast radiation therapy, and to evaluate the comparative effectiveness and costs of an advanced form of breast IORT. IORT is an emerging alternative to whole breast irradiation (WBI), but its current embodiment has several deficiencies including the lack of imaging for target delineation and planning, and poor dosimetry due to the use of low-energy photons. We have leveraged advanced CT-guided, high dose-rate brachytherapy techniques to develop Precision Breast IORT (PB-IORT), a novel method that improves upon conventional breast IORT (CB-IORT) through customized, three-dimensional treatment planning and delivery for higher dose, accurate, individualized IORT that better targets the breast tissue. Our phase I safety and feasibility trial established that PB-IORT can safely deliver 12.5 Gy (roughly twice the dose of CB-IORT) to the at-risk breast tissue. We will evaluate the efficacy of PB-IORT in a multi-center Phase II trial that will assess important clinical and immunologic outcomes and will provide data to enable comparative effectiveness studies, addressing the following specific aims: Aim 1: To determine the efficacy of PB-IORT on 5-year local breast cancer recurrence rates. Because PB-IORT delivers a more accurate and higher dose than CB-IORT, we hypothesize that PB-IORT will result in lower rates of local tumor recurrence than CB- IORT, and similar rates compared to WBI. We will also characterize the cosmetic and quality of life outcomes and mammographic changes after PB-IORT. Aim 2: To evaluate the effects of PB-IORT on the immune system. We will use blood samples from patients treated with PB-IORT and a comparison cohort of WBI-treated to provide fundamental insights into the impact of RT volume and fractionation on immune-suppressive effects of breast RT, determining whether IORT can avoid the immune-suppressive effects of WBI. Aim 3: To evaluate the comparative effectiveness of PB-IORT compared to treatment alternatives. We will apply Markov modeling methods to compare PB-IORT to all other options for breast RT. We will consider how variations in patient preference and recurrence risk impact outcomes and how reimbursement rates would impact cost effectiveness. We will evaluate the costs of PB-IORT using time-driven activity-based costing to inform value-based reimbursement decisions, providing policy-relevant evidence important for dissemination. Our two-institution team provides a foundation for expansion of PB-IORT to facilities without an integrated image-guided brachytherapy suite. As a technically optimized form of IORT, PB-IORT may may ultimately improve patient outcomes and satisfy patient demand by providing an optimized, more effective form of IORT that will reduce recurrences compared to CB-IORT, and will better preserve immune function compared to WBI while reducing health care costs.

我们的建议旨在提高术中放射治疗（IORT）治疗早期肿瘤的疗效。 分期乳腺癌，研究乳腺放射治疗的免疫效果，并评估 先进形式的乳房 IORT 的比较效果和成本。 IORT 是一种新兴的替代方案 全乳腺照射（WBI），但其目前的实施方案存在一些缺陷，包括缺乏成像 用于目标描绘和规划，以及由于使用低能光子而造成的剂量测定不良。我们已经利用杠杆 先进的 CT 引导、高剂量率近距离放射治疗技术，用于开发精准乳腺 IORT (PB-IORT)， 一种通过定制的三维立体图像改进传统乳房 IORT (CB-IORT) 的新颖方法 治疗计划和实施，以实现更高剂量、准确、个性化的 IORT，更好地针对乳房 组织。我们的第一阶段安全性和可行性试验表明 PB-IORT 可以安全地提供 12.5 Gy（大约是 CB-IORT 的剂量）对有风险的乳腺组织。我们将在多中心评估 PB-IORT 的疗效 II 期试验将评估重要的临床和免疫学结果，并提供数据以实现 比较有效性研究，解决以下具体目标： 目标 1：确定 PB-IORT 对 5 年局部乳腺癌复发率的影响。因为 PB-IORT 提供了更准确、更高的 剂量高于 CB-IORT，我们假设 PB-IORT 会导致局部肿瘤复发率低于 CB- IORT，以及与 WBI 相似的比率。我们还将描述美容和生活质量结果 以及 PB-IORT 后乳房 X 光检查的变化。目标 2：评估 PB-IORT 对免疫系统的影响。 我们将使用来自接受 PB-IORT 治疗的患者的血液样本以及接受 WBI 治疗的患者的对照队列 提供关于 RT 体积和分次对免疫抑制作用的影响的基本见解 乳房 RT，确定 IORT 是否可以避免 WBI 的免疫抑制作用。目标 3：评估 PB-IORT 与其他治疗方案相比的有效性比较。我们将应用马尔可夫模型 将 PB-IORT 与所有其他乳房 RT 方案进行比较的方法。我们将考虑患者的差异 偏好和复发风险影响结果以及报销率如何影响成本效益。 我们将使用时间驱动的基于活动的成本核算来评估 PB-IORT 的成本，以告知基于价值的成本 报销决定，提供对传播很重要的政策相关证据。我们的两个机构 团队为将 PB-IORT 扩展到没有集成图像引导的设施提供了基础 近距离放射治疗套件。作为 IORT 的技术优化形式，PB-IORT 可能最终改善患者的病情 通过提供优化的、更有效的 IORT 形式来满足结果并满足患者需求，这将减少 与 CB-IORT 相比，复发率更高，并且与 WBI 相比，可以更好地保留免疫功能，同时减少 医疗保健费用。