LINEAR PD SOURCES FOR PROSTATE BRACHYTHERAPY

前列腺癌困扰着20多万新患者，其中非洲裔美国人的数量不成比例地多，每年导致41,800人死亡。近距离放射治疗是治疗前列腺癌的一种有效方法，(2)越来越多的患者选择近距离放射治疗。当代近距离放射治疗种子由包裹在钛外壳中的125I或(103)Pd组成。每个种子都被设计成类似于具有各向同性分布的点源。实际上，剂量各向异性高达60%(3)。种子通常不能精确传递，最终会错位，并容易迁移，导致肿瘤剂量不足的可能性。生产种子的方法是初级的、低效的、劳动密集型的和昂贵的。这一第二阶段的应用扩大了在线源的生产、评估和剂量测定方面非常成功的工作：将扩大源制造规模；将引入新的输送系统；将扩大导线的剂量测定，以包括剂量图谱和改进的治疗计划“。确定导线与种子的等效性所需的信息将提交给FDA；线性信号源的安全性将在动物模型和临床研究中进行评估。拟议的商业应用：用于治疗前列腺癌的近距离放射治疗方法的市场渗透率预计将在5年内从目前的10%-15%增加到50%以上。(4)通过植入种子进行组织间近距离放射治疗是FDA批准的，得到了广泛接受，并被联邦医疗保险和其他报销计划覆盖。这里提出的进一步开发的线性源是兼容的，但在许多方面优于种子。通过在临床环境中证明这种相对于种子的优势，再加上预期的经济优势，线性源的早期商业成功将很容易建立。随着时间的推移，线性放射源有望取代前列腺近距离放射治疗市场的种子。

Prostate cancer afflicts over 200,000 new patients, with a disproportionately large number of African-Americans, and causes 41,800 deaths(1) each year. Brachytherapy is an effective process for prostate cancer treatment,(2) and is being selected by a rapidly increasing proportion of patients. Current generation brachytherapy seeds consist either of 125I or (103)Pd encapsulated in titanium shells. Each seed is designed to resemble a point source with an isotropic distribution. In reality, the dose anisotropy is as much as 60%(3). The seeds are often not delivered with precision, end up misaligned, and are subject to migration, leading to the possibility of inadequate dose to the tumor. The method of manufacturing seeds is rudimentary, inefficient, labor intensive, and costly. This Phase II application expands the highly successful work on the production, evaluation, and dosimetry of linear sources: source manufacturing will be scaled up; a new delivery system will be introduced; the dosimetry of the wires will be expanded to include a dose atlas and improved treatment planning". The information necessary to establish equivalence of the wires to seeds will be submitted to the FDA; the safety of the linear sources will be evaluated in an animal model and in a clinical study. PROPOSED COMMERCIAL APPLICATIONS: Penetration of the market for the brachytherapy modality for treatment of prostate cancer is expected to increase from the current 10-15% to over 50% in 5 years.(4) Interstitial brachytherapy by placement of seeds is FDA approved, well accepted, and covered by Medicare and other reimbursement plans. The linear sources proposed here for further development are compatible, yet superior in many ways to seeds. By proving this superiority to seeds in a clinical setting, together with the expected economic advantages, early commercial success of the linear sources will readily be established. In time, the linear sources are expected to replace seeds in the prostate brachytherapy market.