Prostate Edema in Permanent Interstitial Brachytherapy

描述（由申请人提供）：永久性间质近距离放射治疗（PIB）用于早期器官局限性前列腺癌，包括在前列腺中植入约100个放射源的永久性手术，以便治疗放射剂量可以传递到癌细胞，同时将对周围正常组织的剂量降至最低。这种方法的潜在优点包括对癌细胞进行连续照射，减少细胞周期依赖性变化对细胞放射敏感性的影响；减少对正常组织的剂量，从而增加肿瘤剂量以加强肿瘤控制；使用一次性植入手术，这比通常持续6周以上的外部放射治疗（EBRT）的每日分次治疗更方便患者；避免了由于日常患者设置的不确定性以及EBRT中分数器官之间和分数器官内部运动而导致的潜在有害的几何缺失。为了充分发挥PIB的潜力，必须能够准确地将这些源放置在预先设计的空间模式中，以产生足够的肿瘤覆盖，并且必须在长时间的PIB剂量传递过程中保持初始源位置，此外还要准确表征每个源的剂量学特性。然而，在前列腺PIB中，植入后源位置的变化是不可避免的，因为手术引起的水肿会导致前列腺迅速膨胀（达到术前体积的两倍），然后逐渐消退，可能需要一个多月的时间。最近的一些研究表明，水肿引起的前列腺体积和源位置的变化可能导致肿瘤剂量的巨大变化，如果忽视这一点，可能会对发展为中度或重度水肿的患者产生有害后果。随着最近一种新的131c源的引入和临床应用，这已经成为一个特别紧迫的问题，它比以前使用的放射性核素具有更短的放射性衰变半衰期（9.7天），因此对水肿引起的源位置变化更敏感。该项目的具体目标是：1)开发一种新的综合方法来准确测定水肿的剂量效应，以便在有或没有放射生物学指导的情况下设计有效的治疗干预策略并将其纳入PIB的计划和治疗中；2)通过测量15例PIB患者的水肿演变史，对提出的方法和现有的水肿模型进行系统验证；3)综合评价水肿引起的剂量变化的临床意义和治疗干预策略的有效性，使PIB的疗效能够针对每个患者进行优化。我们假设，该项目的成功完成将使临床有效地管理前列腺水肿对每个患者的影响，从而有助于充分发挥PIB治疗早期前列腺癌的潜力。公共卫生相关性：在前列腺内永久植入含有碘-125、钯-103或铯-131的放射性粒子，也称为近距离放射治疗，已成为一种受欢迎的放射治疗形式，用于精心挑选的前列腺癌患者。近距离放射治疗的临床成功高度依赖于正确计划手术、植入放射源和进行剂量测定的能力，以确保辐射剂量分布明确并适合肿瘤的最佳治疗。然而，这种能力一直受到不可避免的发展和手术引起的前列腺水肿的解决的阻碍，这可能持续一个多月。本课题的主要目的是开发一种新的方法，在放射剂量测定和治疗计划中考虑水肿的影响，以便为每个患者提供最佳的治疗效果。

DESCRIPTION (provided by applicant): Permanent interstitial brachytherapy (PIB) for early stage organ-confined prostate cancer involves permanent surgical implantation of about 100 radioactive sources into the prostate so that a therapeutic radiation dose can be delivered to the cancer cells while minimizing the doses to the surrounding normal tissues. Potential advantages of this approach include continuous irradiation of cancer cells which reduces the impact of cell- cycle dependent variations in cellular radiosensitivity; reduced dose to normal tissues, which allows escalation of tumor dose for increased tumor control; use of a one-time implant procedure, which is more convenient for patients than the fractionated daily treatments of external beam radiotherapy (EBRT) that often last more than six weeks; and the avoidance of potentially detrimental geometric misses caused by the uncertainties in daily patient setup and by inter- and intra-fractional organ motions in EBRT. To fully achieve the potential of PIB, one must be able to accurately place these sources in a pre-designed spatial pattern for producing adequate tumor coverage and must maintain the initial source positions during the protracted PIB dose delivery, in addition to having an accurate characterization of the dosimetric properties of each source. In prostate PIB, however, variation in post-implant source position is inevitable because edema induced by the surgical procedure causes the prostate gland to swell rapidly (to as large as twice of its pre-surgery volume) followed by a gradual resolution that can require more than a month. A number of recent studies have shown that edema-induced variations in prostate volume and source positions can lead to large variations in the dose delivered to the tumor, which, if ignored, can have detrimental consequences for patients developing moderate or severe edema. This has become an especially urgent issue with the recent introduction and clinical application of a new 131Cs source, which has a shorter radioactivity decay half-life (9.7 day) than radionuclides used previously and therefore is more sensitive to the edema-induced source position variations. The specific aims of this project are: 1) to develop a new and integrated approach for accurate determination of the dosimetric effects of edema so that effective therapeutic intervention strategies can be designed and integrated into the planning and treatment of PIB with or without radiobiology guidance; 2) to conduct a systematic validation of the proposed approach and the existing edema models using the histories of edema evolution measured for 15 PIB patients; and 3) to perform a comprehensive evaluation of the clinical significance of edema-induced dosimetric variations and the effectiveness of therapeutic intervention strategies so that the efficacy of PIB can be optimized for each individual patient. We hypothesize that the successful completion of this project will enable effective clinical management of the effects of prostate edema for each patient and thereby help to achieve the full potential of PIB in the treatment of early-stage prostate cancer. Public Health Relevance: Permanent implantation of radioactive seeds containing iodine-125, palladium-103, or cesium-131 in the prostate, also called brachytherapy, has become a popular form of radiation therapy for carefully selected prostate cancer patients. The clinical success of brachytherapy is highly dependent on the ability to properly plan the procedure, implant the radioactive source, and perform dosimetry in a way that ensures that the radiation dose distributions are well defined and appropriate for optimal treatment of the tumor. This ability, however, has been hampered by the inevitable development and resolution of surgery-induced prostate edema, which can last over a month. The primary objective of this project is to develop a new method to consider the effects of edema in radiation dosimetry and treatment planning so that the efficacy of this therapy can be optimized for each patient.