Increasing nerve-sparing radical prostatectomy rates using intraoperative nonlinear microscopy

使用术中非线性显微镜提高保留神经的根治性前列腺切除术率

• 批准号: 10548166
• 负责人: JAMES G FUJIMOTO
• 金额: $ 46.4万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-05 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10548166
• 关键词: Adoption; Agreement; Apical; Area; Blinded; Cancer Patient; Clinic; Clinical; Color; Consultations; Control Groups; Custom; Cytoplasm; Data; Decision Making; Development; Evaluation; Excision; Fluorescence; Formalin; Freezing; Frozen Sections; Histology; Hospitals; Human Resources; Image; Imaging Techniques; Impotence; Incontinence; Infrastructure; Israel; Judgment; Lasers; Lateral; Malignant Neoplasms; Malignant neoplasm of prostate; Massachusetts; Medical center; Methods; Microscopy; Microtome - medical device; Nerve; Nerve-Sparing Prostatectomy; Notification; Nuclear; Operative Surgical Procedures; Outcome; Paraffin Embedding; Pathologist; Pathology; Patients; Performance; Persons; Population; Postoperative Care; Postoperative Period; Preparation; Procedures; Prostate; Prostate Cancer therapy; Prostatectomy; Protocols documentation; Quality of life; Radical Prostatectomy; Randomized, Controlled Trials; Reading; Recovery; Research Personnel; Residual Cancers; Robotics; Scanning; Screening for Prostate Cancer; Sex Functioning; Signal Transduction; Site; Specificity; Specimen; Stains; Surgeon; Surgical margins; Technology; Time; Tissues; arm; cost; cryostat; high resolution imaging; improved; instrument; male; medical schools; microscopic imaging; multidisciplinary; neurovascular; next generation; novel strategies; point of care; primary endpoint; programs; prostate surgery; rapid technique; remote assessment; secondary endpoint; spared nerve; standard of care; tumor

Prostate cancer is the most common cancer in the US male population, with an estimated 160,000 new cases in 2018. Treatment with radical prostatectomy (RP), complete surgical excision of the prostate, results in favorable oncologic outcomes with long-term survival benefits. Nerve-sparing RP is favored if cancer does not involve the neurovascular bundles since patients have better recovery of sexual function and continence, major factors determining postoperative quality of life. However current preoperative methods do not accurately identify patients who could be treated by nerve-sparing RP. The NeuroSAFE study, Schlomm, et al., 2012 demonstrated that comprehensive intraoperative frozen section analysis (FSA) of margins near the neurovascular bundles increased the rate of nerve-sparing RPs. However comprehensive intraoperative FSA required extensive time and personnel, which is impractical for most hospitals. Nonlinear microscopy (NLM) can generate images of freshly excised tissue resembling H&E histology, without freezing or microtoming, reducing the time and labor required for pathology evaluation. We developed custom NLM technology and specimen handing/staining protocols for rapid, high-throughput evaluation of prostatectomy specimens. Our preliminary data demonstrates that NLM detects prostate cancer with 97% sensitivity and 100% specificity compared to formalin fixed paraffin embedded (FFPE) H&E in a study of 122 RP specimens from 40 patients with blinded reading by three pathologists. NLM promises to enable intraoperative evaluation of RP specimens with a simplified workflow that is practical for widespread clinical adoption. Our hypothesis is: NLM can be used to rapidly assess prostate surgical specimens and increase nerve-sparing RP rates without increasing positive margin rates. This is a collaborative, multidisciplinary program with investigators at the Massachusetts Institute of Technology and Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School. Aim 1 will develop next generation NLM technology and clinical workflow for rapid, comprehensive evaluation of prostate specimens in RP. These advances will enable a two person team (histotech/resident and pathologist) to perform comprehensive NLM of RP margins adjacent to the neurovascular bundles, faster and with much fewer personnel than NeuroSAFE. Aim 2 will perform a randomized controlled trial with patients undergoing robotic RP. The primary endpoints will be the rate of nerve-sparing RPs and rate of positive surgical margins in areas adjacent to the neurovascular bundles in a study group receiving intraoperative NLM margin assessment and standard-of-care postoperative FFPE histology versus a control group receiving standard-of-care FFPE postoperative histology. The secondary endpoints will be agreement between intraoperative NLM versus postoperative histology in the study arm and surgical times in the study arm versus control arm. Aim 3 will develop NLM technology and workflows that enable remote NLM evaluation which would increase access to pathologists with subspecialty expertise, streamline pathologist workflow, and facilitate adoption of intraoperative margin assessment in RP.

前列腺癌是美国男性最常见的癌症，估计有160,000例新病例 在2018年。从根治性前列腺切除术（RP）治疗，对前列腺的完全手术切除，导致 具有长期生存益处的有利肿瘤学结果。如果癌症没有 涉及神经血管束，因为患者的性功能和延续性更好 决定术后生活质量的因素。但是，目前的术前方法无法准确识别 可以通过神经治疗的RP治疗的患者。 Neurosafe研究，Schlomm等人，2012年证明了 神经血管束附近边缘的全面术中冷冻部分分析（FSA） 提高了神经保留的RP的速度。但是，术中全面的FSA需要大量时间 和人员，对于大多数医院来说都是不切实际的。非线性显微镜（NLM）可以生成 新鲜切除的组织类似于H＆E组织学，没有冷冻或微功能，减少时间和劳动 病理评估所必需的。我们开发了定制的NLM技术和标本交接/染色 快速，高通量评估的前列腺切除术标本的方案。我们的初步数据证明了 NLM与福尔马林固定石蜡相比检测到具有97％敏感性和100％特异性的前列腺癌 嵌入（FFPE）H＆E在一项研究40例盲目阅读患者的122个RP标本中 病理学家。 NLM有望通过简化的工作流程对RP样本进行术中评估 对于广泛的临床采用是实用的。我们的假设是：NLM可用于快速评估前列腺 手术标本并提高神经疗程的RP率，而没有增加正差率。这是一个 马萨诸塞州技术学院与贝丝的调查人员的合作，多学科计划 哈佛医学院以色列女执事医疗中心（BIDMC）。 AIM 1将发展下一代NLM 用于快速，全面评估前列腺标本的技术和临床工作流程。这些 进步将使一个两人团队（Histotech/居民和病理学家）能够执行全面的NLM 与神经血管束相邻的RP边缘，比神经防护更快，人员少得多。 AIM 2将对接受机器人RP的患者进行随机对照试验。主要终点将 成为神经疗法的RP的速度和与神经血管相邻区域的阳性手术边缘的速率 接受术中NLM边缘评估和护理标准术后的研究组中的捆绑 FFPE组织学与接受护理标准FFPE术后组织学的对照组。次要 终点将是研究部门的术中NLM与术后组织学之间的一致 研究臂与对照组的手术时间。 AIM 3将开发NLM技术和工作流程 远程NLM评估将增加具有专业知识的病理学家的访问权限，精简 病理学家的工作流程，并促进RP中采用术中的边缘评估。