Integrated Image-Guided Dosimetry and Treatment Planning for Photodynamic Therapy

光动力治疗的集成图像引导剂量测定和治疗计划

• 批准号: 9187830
• 负责人: GAL SHAFIRSTEIN
• 金额: $ 48.98万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-01 至 2020-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9187830
• 关键词: Ablation; Affect; Anatomy; Animal Model; Animals; Basal cell carcinoma; Cancerous; Carcinoma; Clinical; Clinical Research; Complex; Computer Simulation; Data; Diffuse; Disease; Dose; Drug-sensitive; European Union; FDA approved; Fiber; Geometry; Goals; Head and Neck Cancer; Histopathology; Imaging Techniques; Implant; Label; Lasers; Length; Light; Lighting; Locally Advanced Malignant Neoplasm; Location; Malignant Neoplasms; Measures; Mediating; Minor; Modeling; Molecular Analysis; Monitor; Mus; New Zealand; Oryctolagus cuniculus; Outcome; Oxygen; PUVA Photochemotherapy; Patients; Peer Review; Pharmaceutical Preparations; Photosensitization; Porfimer Sodium; Pre-Clinical Model; Publications; Research Proposals; Safety; Stat3 protein; System; Technology; Testing; Therapeutic; Time; Tumor Oxygenation; Ultrasonography; Work; X-Ray Computed Tomography; base; clinical practice; clinically relevant; crosslink; dosimetry; effective therapy; expectation; experience; experimental study; image guided; improved; interstitial; novel; pre-clinical; preclinical study; public health relevance; response; subcutaneous; treatment planning; tumor

 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.

 描述（由申请人提供）：本研究提案旨在改善局部晚期头颈癌（LAHNC）患者的间质光动力治疗（I-PDT），目前对于这些患者尚无有效的全身治疗方法。施用光敏药物（光敏剂，PS）后用扩散纤维进行瘤内照明，我们最近使用 I-PDT 和卟啉钠治疗了 5 名 LAHNC 患者。 （Photofrin），FDA 批准的光敏剂（PS），在这些情况下，我们使用了我们的治疗计划和剂量测定系统（综合剂量测定系统），并得到了当地 IRB 和 FDA 的批准。在同行评审的出版物中提供我们的技术原理证明，但是，根据我们在头部和 PDT 中使用外部光束 (EB) 照明的丰富经验，肿瘤反应令人失望且与我们的预期不一致。脖子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注量率，已知这会对 Photofrin 的 PDT 功效产生不利影响。因此，我们确信这种​​高注量率。我们规定肿瘤内注量率对于使用 Photofrin 进行有效的 I-PDT 至关重要。在本提案中，我们将首先利用我们新颖的综合治疗计划和剂量测定系统的功能来定义。时间、Photofrin 介导的 I-PDT 的最佳肿瘤内注量率和注量，我们认为我们的综合治疗计划和剂量测定系统具有最佳的光注量率和注量，将改善 LAHNC 对 I-PDT 的反应。 ，我们建议采用逐步方法，以实现以下目标： 目标 1. 使用我们的临床前模型中的光剂量测定系统定义 Photofrin I-PDT 的最佳注量率和注量。表明我们可以在临床前和临床环境中监测 I-PDT 期间的肿瘤内光注量率和注量我们将定义动物的最佳注量率和注量。 目标 2. 建立 LAHNC 患者 Photofrin I-PDT 的最佳注量率。因此，在完成拟议的目标时，我们将显着提高 I-PDT 对没有有效治疗的 LAHNC 患者的潜在益处。最大限度地提高 I-PDT 对 LAHNC 患者的治疗效果 目前提案的更广泛影响是验证一个有潜力改善其他解剖部位局部晚期癌症的 I-PDT 治疗的系统。