MR Guided Laser Ablation of Prostate Cancer: Phase II Trial

描述(申请人提供)：前列腺癌是美国男性癌症相关死亡的主要原因。前列腺癌的标准治疗方法是全腺体治疗，包括根治性前列腺癌切除术和放射治疗。越来越多的证据表明，前列腺癌被过度治疗，在许多接受积极治疗的患者的自然生命期间，前列腺癌可能在临床上并不明显。全腺治疗方法也与改变生活质量的并发症的高风险有关，如大小便失禁和阳萎。基于这些事实，人们建议对低危前列腺癌采取不会出现严重并发症、但旨在从一开始就控制癌症的局部治疗方法。在这些方法中，MRI引导下的激光诱导热疗(LIT)是一种很有前途的技术，与其他病灶治疗方法相比具有一定的优势。它可以在前列腺内创建准确、可预测和可重复的消融区，并在目标消融区之外引起最小的变化。它与MRI兼容，因此可以受益于用于治疗计划的卓越软组织对比分辨率和用于实时治疗监测的MR热成像。我们的团队最近完成了一项第一阶段的研究，证明了技术上的可行性，并确认了这一过程的初步安全性。本提案的目标是 在MRI引导下进行前列腺癌靶向毁损LITT的II期临床试验。我们假设MR引导的LITT将有效地消融前列腺癌的靶区，表现出特殊的长期安全性，并且不会改变尿路或性生活质量。具体目标是(1)我们将进行II期非随机单臂临床试验，严格评估MRI引导下的LITT在新诊断前列腺癌患者中的肿瘤学疗效。主要终点将是在激光消融3个月后进行MR引导下的活检，以确认治疗区域内没有癌症。次级终点将是基于治疗后12个月治疗区域活组织检查的肿瘤学疗效，以及用经过验证的仪器测量与治疗相关的安全性和毒性。(2)我们将实施定量和解剖MR成像，跟踪每个治疗区域和周围组织，以确定消融区MR成像特征的变化。分别于治疗前、治疗后3个月和12个月进行动态增强(DCE)、弥散加权成像(DWI)、定量T2加权成像和高分辨率解剖成像。治疗后MRI的结果将与术后3个月和12个月进行的活组织检查进行比较。在这个项目完成时，我们将使用MR引导的LITT治疗27名患者，并将获得关于MRI的肿瘤学有效性、安全性和预测作用的极有价值的信息。随后，我们将利用这些结果来支持一项更大规模的多中心试验的设计，以评估这种新的局部治疗范例的相对有效性。

DESCRIPTION (provided by applicant): Prostate cancer is a major cause of cancer related deaths in American men. Standard treatment of prostate cancer has been whole-gland treatment including radical prostatectomy and radiation therapy. There is growing evidence that prostate cancer is over-treated and prostate cancer may not be clinically evident during the natural life span of many patients who are aggressively treated. Whole-gland treatment methods have also been associated with high risk of complications altering quality of life such as incontinence and impotence. Based on these facts, focal treatment methods which are not associated with serious complications but aim to control the cancer at the outset have been suggested as alternative treatment methods for low-risk prostate cancer. Among these methods, MRI guided laser induced thermal therapy (LITT) is a promising technique with certain advantages over the other focal therapy methods. It can create accurate, predictable and reproducible ablation zones within the prostate and induces minimal change outside the targeted ablation zone. It is compatible with MRI and therefore, can benefit from superior soft tissue contrast resolution for treatment planning and MR thermography for real time therapy monitoring. Our group has recently completed a Phase I study and demonstrated the technical feasibility and confirmed the initial safety of this procedure. The goal of the present proposal is to conduct a phase II clinical trial with MRI-guided LITT for targeted focal destruction of prostat cancer. We hypothesize that MR-guided LITT will effectively ablate target areas of prostate cancer, exhibit an exceptional long term safety profile, and will not alter urinary or sexual qualiy-of-life. The specific aims are (1) We will conduct a Phase II non-randomized, single-arm clinical trial to rigorously assess oncologic effectiveness of MRI guided LITT in patients with newly diagnosed prostate cancer. Primary endpoint will be confirmation of lack of cancer within the treatment zone by an MR guided biopsy performed 3 months after laser ablation. Secondary endpoints will be oncologic efficacy based on biopsy of the treatment zone at 12 months following treatment and treatment-related safety and toxicity measured with validated instruments. (2) We will implement quantitative and anatomic MR imaging to follow each treated region and surrounding tissue to define alterations in the MR imaging features of the ablation zone. Dynamic contrast enhanced (DCE) imaging, diffusion weighted imaging (DWI), quantitative T2-weighted imaging and high resolution anatomic imaging will be collected prior to treatment and at 3 months and 12 months following treatment. The results of post-treatment MRI's will be compared to biopsies performed at 3 months and 12 months following the procedure. At the completion of this project, we will have treated 27 patients using MR-guided LITT and will have gained highly valuable information regarding oncologic efficacy, safety, and predictive role of MRI. We will subsequently use these results to support the design of a larger multi-center trial to evaluate the comparative effectiveness of this new focal treatment paradigm.