Integrated Image-Guided Dosimetry and Treatment Planning for Photodynamic Therapy

 描述(申请人提供)：本研究方案旨在改善局部晚期头颈癌(LAHNC)患者的间质光动力疗法(I-PDT)。目前还没有针对这些患者的有效治疗方法。在I-PDT中，全身给予一种光敏药物(光敏剂，PS)，然后用扩散光纤进行肿瘤内照射(S)。我们最近使用I-PDT和FDA批准的光敏剂(PS)--波菲尔钠(Photofrin)治疗了5名LAHNC患者。这些患者在标签外接受了治疗，并进行了初步的临床研究。在这些环境中，我们使用我们的治疗计划和剂量测定系统(集成剂量测定系统)，并获得当地IRB和FDA的批准，在同行评议的出版物中提供我们技术的原则证明。我们的系统按计划运行。然而，肿瘤的反应令人失望，与我们的期望不一致，这是基于我们在头颈癌PDT中使用外部光束(EB)照射的大量经验。我们的计算机模拟和初步动物研究表明，传统上用于扩散纤维的激光设置将导致非常高的肿瘤内流变率，这已知会对使用Photofrin的PDT的疗效产生不利影响。因此，我们确信这种高注量率并不是最优的。我们规定，最佳的瘤内注量率是使用Photofrin进行有效的I-PDT的关键。在这项提案中，我们将利用我们的新型综合治疗计划和剂量学系统的力量，首次确定Photofrin介导的I-PDT的最佳瘤内注量率和注量。我们假设，我们集成的治疗计划和剂量测定系统，具有最佳的光通量比率和光通量，将改善LAHNC对I-PDT的反应。为了验证这一假设，我们提出了一种循序渐进的方法，目的如下：1.在临床前模型中，使用我们的光剂量学系统确定Photofrin I-PDT的最佳注量率和注量。我们的初步数据显示，我们可以在临床前和临床环境下监测I-PDT期间肿瘤内的光通量和光通量。我们将在动物身上定义最佳的注量率和注量 用简单的肿瘤几何模型，并在更复杂的几何和解剖位置的临床前模型中测试最佳注量率和注量。目的2.建立LAHNC患者Photofrin I-PDT的最佳剂量率。本研究的目的是确定LAHNC患者的最佳剂量率。因此，在完成拟议的目标后，我们将显著提高I-PDT对没有有效治疗的LAHNC患者的潜在益处。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了一种系统，该系统有可能改善对其他解剖部位局部晚期癌症的I-PDT的管理。

 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.