Integrated Image-Guided Dosimetry and Treatment Planning for Photodynamic Therapy

 描述（由申请人提供）：本研究计划旨在改善局部晚期头颈癌（LAHNC）患者的间质光动力治疗（I-PDT）。目前对这些患者没有有效的治疗方法。在I-PDT中，全身施用光敏药物（光敏剂，PS）之后用漫射纤维进行肿瘤内照射。我们最近使用I-PDT和porfimer钠（Photofrin）（FDA批准的光敏剂（PS））治疗了5例LAHNC患者。这些患者在一项初步临床研究中接受标签外治疗。在这些环境中，我们使用了我们的治疗计划和剂量测定系统（集成剂量测定系统），并获得了当地IRB和FDA的批准，在同行评审出版物中提供了我们技术的原理证明。我们的系统按计划运行。然而，肿瘤反应是令人失望的，并与我们的预期不一致，根据我们的大量经验与外部光束（EB）照明的PDT的头部和颈部癌症。我们的计算机模拟和初步动物研究表明，历史上扩散纤维的激光设置将导致非常高的肿瘤内荧光，这是已知的不利影响PDT与Photofrin的疗效。因此，我们确信这种高注量率不是最佳的。我们规定，最佳的瘤内注量率是必不可少的一个有效的I-PDT与Photofrin。在这项提案中，我们将采用我们的新的综合治疗计划和剂量测定系统的权力，以定义，为第一次，最佳的肿瘤内通量率和通量Photofrin介导的I-PDT。我们假设，我们的综合治疗计划和剂量测定系统，与最佳的光通量率和通量，将提高响应I-PDT的LAHNC。为了检验这一假设，我们建议采取一种逐步的方法，其目标如下：目标1。在临床前模型中使用我们的光剂量测定系统确定Photofrin I-PDT的最佳注量率和注量。我们的初步数据表明，我们可以监测肿瘤内的光通量率和通量在I-PDT在临床前和临床设置。我们将定义动物的最佳注量率和注量 模型与简单的肿瘤几何形状，并测试最佳的注量率和注量在临床前模型更复杂的几何形状和解剖位置。目标2.确定LAHNC患者Photofrin I-PDT的最佳注量率。本研究的目的是确定LAHNC患者的最佳注量率。因此，在完成提出的目标，我们将显着推进I-PDT的潜在利益与LAHNC患者，谁没有有效的治疗。我们的最终目标是最大限度地提高I-PDT对LAHNC患者的治疗效果。当前提案的更广泛影响是验证一种系统，该系统有可能改善其他解剖部位局部晚期癌症的I-PDT给药。

 DESCRIPTION (provided by applicant): This research proposal aims at improving interstitial photodynamic therapy (I-PDT) for patients with locally advanced head and neck cancer (LAHNC). Currently there is no effective treatment for these patients. In I- PDT, systemic administration of a light sensitive drug (photosensitizer, PS) is followed by intratumoral illumination with diffusing fiber(s). We have recently treated five patients with LAHNC using I-PDT and porfimer sodium (Photofrin), the FDA approved photosensitizer (PS). These patients were treated off label and in a pilot clinical study. In these settings we used our treatment planning and dosimetry system (integrated dosimetry system), with approval from the local IRB and FDA, to provide a proof of principle of our technology in a peer reviewed publication. Our system worked as planned. However, tumor response was disappointing and inconsistent with our expectations based on our large experience with external beam (EB) illumination in the PDT of head and neck cancer. Our computer simulations and preliminary animal studies suggest that the historically laser setting for diffusing fibers will result in a very high intratumoral fluencerate, which is known to adversely affect the efficacy of PDT with Photofrin. Thus, we are convinced that this high fluence rate is not optimal. We stipulate that optimal intratumoral fluence rate is essential for an effective I-PDT with Photofrin. In this proposal, we will employ the power of our novel integrated treatment planning and dosimetry system to define, for the first time, the optimal intratumoral fluence rate and fluence for Photofrin mediated I-PDT. We hypothesize that our integrated treatment planning and dosimetry system, with optimal light fluence rate and fluence, will improve the response to I-PDT of LAHNC. To test this hypothesis, we propose to pursue a stepwise approach with the following aims: Aim 1. Define optimal fluence rate and fluence for Photofrin I-PDT with our light dosimetry system in preclinical models. Our preliminary data show that we can monitor intratumoral light fluence rate and fluence during I-PDT in both preclinical and clinical settings. We will define the optimal fluence rate and fluence in an animal model with simple tumor geometry, and test the optimal fluence rate and fluence in a preclinical model of more complex geometry and anatomical location. Aim 2. Establish the optimal fluence rate for Photofrin I-PDT in patients with LAHNC. The objective of this aim is to determine the optimal fluence rate in patients with LAHNC. Hence, in completing the proposed aims, we will significantly advance the potential benefit of I-PDT for patients with LAHNC, who have no effective therapy. Our ultimate goal is to maximize the therapeutic benefits of I-PDT for patients with LAHNC. The wider impact of the current proposal is in validating a system that has the potential to improve the administration of I-PDT for locally advanced cancer in other anatomical sites.