Real-time volumetric specimen imager for 3D intra-operative lumpectomy margin assessment

摘要 Clarix成像公司(Clarix)致力于解决早期乳房的最大问题之一 癌症治疗，利润率为正的再手术。在接受治疗的20万名患者中，约有25% 在美国，肿块切除术每年都将面临这种额外的程序，因为目前识别 术中正向利润率不足。目前，医生依靠2D标本成像来进行 评估手术中的边缘状态，但不能充分反映手术的3D边缘形态 肿瘤。因此，Clarix正在开发一种新型的体积样品成像仪VSI，它可以产生全3D图像 具有各向同性分辨率的标本图像，可以显著提高边际评估和 在缝合伤口前，为定向口腔剃须刀提供精确的指导。在第一阶段，我们演示了 我们的VSI专利算法能够克服传统3D成像仪的长扫描时间，这将 一项20例回顾性先导研究中的扰乱外科治疗。在第二阶段，我们开发了一个健壮的原型， 硬件设计用于用户的易用性和安全性，软件用于用户友好或工作流集成。 这种向可生产原型的转移在230名患者的大规模回顾中得到了进一步验证 学习。第二阶段产生的VSI设备的初始FDA 510(K)申请将于2019年第三季度提交。 我们现在为第二阶段B项目提出四个具体目标，以帮助Clarix弥合 技术开发和商业化情况如下。目标1，“为进一步改进而开发软件 临床工作流程和放射病理影像数据库“将进一步简化集成到领先的 电子病历系统，并将开发一个将VSI数据和数字配对的数据库 病理记录。目标2：为大规模生产开发VSI设备的制造工艺 才能。目标3：“前瞻性二期临床试验”一项多中心、单臂、100名患者参与的临床试验 初步评估VSI设备将正边际比率降至10%的能力。目标 4：“关键的随机临床试验”这项有600名患者参加的第三阶段试验旨在最终确定 负利润率提高到90%，在这项研究中展示了优于现行标准的优势 将允许FDA具体批准FDA进行利润率评估和广泛采用。6000个美国人 实施肿块切除术的医院和诊所在持续的行动中被鼓励采用VSI 转向基于价值的报销，形成了约7.2亿美元的初始美国安装基础。我们的全球市场是 估计约为40亿美元。在第二阶段B结束时，我们将在地区上证明商业可行性，然后 我们将在国内和国际上扩大规模。

Abstract Clarix Imaging, Corporation (Clarix) is focused on solving one of the largest problems in early stage breast cancer treatment, reoperations for positive margins. About 25% of the >200,000 patients who undergo lumpectomy in the US each year will face this additional procedure because current options for identifying positive margins intraoperatively are insufficient. Currently physicians rely on 2D specimen imaging for assessing margin status during surgery which cannot adequately represent the 3D margin morphology of the tumor. Therefore, Clarix is developing a novel volumetric specimen imager, VSI, device that yields fully 3D images of the specimen with isotropic resolution which can significantly improve margin assessment and provide precise guidance for directed cavity shaves before closing wound. In Phase I, we demonstrated the ability of our VSI patented algorithms to overcome long scan times of conventional 3D imagers that would disrupt surgical in a 20-case retrospective pilot study. In Phase II, we developed a robust prototype with hardware designed for user ease of use and safety, and software for user-friendly OR workflow integration. This transfer to manufacturing ready prototype was further validated in a large-scale 230 patient retrospective study. An initial FDA 510(k) application for the VSI device resulting from Phase II will be submitted in Q3 2019. We now propose four specific aims for a Phase IIB project that will help Clarix bridge the gap between technology development and commercialization as follows. Aim 1, “Develop Software for Further Improved Clinical Workflow and Radiology-Pathology Image Database” will further streamline integration into leading Electronic Medical Record systems, and a database will be developed which will pair VSI data and digital pathology records. Aim 2: “Develop Manufacturing Process for the VSI Device” for large scale manufacturing ability. Aim 3: “Prospective Phase II Clinical Trial” a multi-center single-arm 100 patient clinical trial will be conducted to preliminarily evaluate the ability of the VSI device to decrease positive margin rates to 10%. Aim 4: “Pivotal Randomized Clinical Trial” this 600 patient Phase III trial will be designed to definitively determine improvement in negative margins to 90%, demonstration of superiority over the current standard in this study will allow for specific FDA approval of FDA for margin assessment and widespread adoption. The 6,000 US hospitals and clinics performing lumpectomy are incentivized to adopt VSI under the ongoing movement toward value-based reimbursement, forming a ~$720M initial US installed-base. Our global market is estimated at ~$4B. At the conclusion of Phase IIB we will prove the commercial viability regionally, and then we will scale nationally and internationally.