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

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。 期乳腺癌，研究乳腺放射治疗的免疫效应，并评估 比较先进的乳房IORT形式的有效性和成本。IORT是一种新兴的替代方法， 全乳房照射（WBI），但其当前实施例具有若干缺陷，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导致的不良剂量测定。我们利用 先进的CT引导、高剂量率近距离放射治疗技术，以开发精确乳腺IORT（PB-IORT）， 一种新的方法，通过定制的，三维的， 治疗计划和实施，以实现更高剂量、准确、个性化的IORT，更好地靶向乳腺 组织.我们的I期安全性和可行性试验确定PB-IORT可以安全地提供12.5戈伊（大约两倍） CB-IORT的剂量）。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局，并将提供数据， 比较有效性研究，针对以下具体目标：目标1：确定 PB-IORT对5年局部乳腺癌复发率的影响。由于PB-IORT提供了更准确、更高的 剂量比CB-IORT，我们假设PB-IORT将导致比CB-IORT更低的局部肿瘤复发率。 与WBI相比，IORT和相似的比率。我们还将描述美容和生活质量的结果 和PB-IORT后的乳房X线摄影变化。目的2：探讨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和来自接受WBI治疗的对照队列的血液样本， 提供了RT体积和分级对免疫抑制作用的影响的基本见解， 乳腺RT，确定IORT是否可以避免WBI的免疫抑制作用。目标3：评价 PB-IORT与替代治疗相比的相对有效性。我们将应用马尔可夫模型 比较PB-IORT与所有其他乳腺RT选择的方法。我们将考虑患者 偏好和复发风险影响结果，以及偿还率如何影响成本效益。 我们将使用时间驱动的基于作业的成本计算来评估PB-IORT的成本，以告知基于价值的 报销决定，提供政策相关的证据，传播重要。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 近距离放射治疗室作为一种技术上优化的IORT形式，PB-IORT可能最终改善患者 通过提供一种优化的、更有效的IORT形式， 与CB-IORT相比，它可以更好地保护免疫功能，同时减少 医疗保健费用。

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.