Multi-modality detection of RCC Recurrence Post Ablation

项目摘要：肾细胞癌(RCC)占所有癌症的3-5%。局部消融是一种 推荐治疗T1a肾癌(约占所有肾癌的25%)，对 治疗因肾功能减退或孤立肾脏而不适合手术的患者。 消融后用于检测复发的成像方案各不相同，但主要依靠对比度增强的计算机 每隔3-12个月进行一次断层扫描(CECT)或增强磁共振成像(CEMRI)检查。 然而，可以基于消融腔内的对比度增强的检测来检测复发 在这两种方式上都具有挑战性-因为大多数复发的影像表现是非特异性的，因为 肿瘤大小的变化、脂肪坏死和瘢痕形成的强化以及钙化的发展 在治疗之后。此外，由于形态和造影剂的原因，这些技术可能会有问题 禁忌症。作为CECT和CEMRI的替代方法，对比增强超声(CEUS)已获得 接受各种临床应用。在小规模的试点研究中，我们的团队已经证明了 CEUS以100%的灵敏度监测经皮消融术后残留和复发的肾癌 无不良反应。虽然令人鼓舞，但我们的发现是基于相对较小的样本量，并且 该技术的总体特异度在75%-96%之间，主要是由于无法正确识别 消融腔与周围肾皮质的边界。为了评估CEUS的临床前景，我们 提出一项规模更大、功能齐全的研究，招募跨多个机构的患者，并使用多种模式 影像技术，以克服这些限制，并使临床采用。在我们的第一个具体目标中，我们将 描述两者的敏感度、特异度、阳性和阴性预测值以及读者之间的一致性 2DCEUS和增强横断面成像用于检测消融后复发的肾癌；我们将 以长期随访影像和组织病理学相结合作为参考标准，而不是依赖 在CECT或CEMRI上。在每个地点，具有不同CEU经验水平的盲人放射科医生将解释 考试，使我们能够定义这些参数，同时也量化读者的可变性。在第二个目标中，我们 将评估2D CEUS与患者融合时对定性评估的潜在改善 治疗前的横断面成像，我们假设它将更好地描绘最初的肿瘤 边界。在第三个目标中，我们将评估使用多模式容量CEU的潜在附加值 检测消融术后肾细胞癌复发及一种先进的多普勒非对比成像技术作为探索性方法 对准目标。最后，我们将探索使用从2D/3D CEU检查中提取的定量参数来确定 如果这提高了CEU的整体性能。在研究结束时，我们希望解决目前的 使用全功率CEUS研究支持临床采用的肾癌复发监测成像的局限性， 同时还通过使用多模式和定量成像来解决先前的限制。

Project Summary: Renal cell carcinoma (RCC) accounts for 3-5% of all cancers. Localized ablation is a recommended treatment for T1a renal cancers (approximately 25% of all RCC) and particularly important for the treatment of patients who are poor surgical candidates due to diminished renal function or with a solitary kidney. Post-ablation imaging protocols for detection of recurrence vary, but mainly rely on contrast-enhanced computed tomography (CECT) or contrast-enhanced magnetic resonance imaging (CEMRI) at 3-12 months intervals. However, detection of relapse based on detection of contrast enhancement within the ablation cavity can be challenging on both modalities – due to most imaging findings of recurrence being nonspecific because of changes in tumor size, enhancement from fat necrosis and scarring, and the development of calcifications following therapy. Additionally, these techniques can be problematic due to modality and contrast agent contraindications. As an alternative to CECT and CEMRI, contrast-enhanced ultrasound (CEUS) has gained acceptance for a variety of clinical applications. In small pilot studies, our group has demonstrated the ability of CEUS to monitor for both residual and recurrent RCC following percutaneous ablation with 100% sensitivity and no adverse events. While encouraging, our findings were based on a relatively small sample size and, with an overall specificity of the technique that ranged from 75-96%, primarily due to an inability to properly identify the boundaries of the ablation cavity from the surrounding renal cortex. To assess the clinical promise of CEUS, we propose a larger, fully powered study, recruiting patients across multiple institutions and using multi-modality imaging techniques to overcome these limitations and enable clinical adoption. In our first specific aim, we will characterize the sensitivity, specificity, positive and negative predictive value, and inter-reader agreement of both 2D CEUS and contrast-enhanced cross-sectional imaging for detecting recurrent RCC following ablation; we will use a combination of long-term follow-up imaging and tissue pathology as a reference standard, instead of relying on CECT or CEMRI. At each site, blinded radiologists with varying experience levels in CEUS will interpret exams, enabling us to define these parameters while also quantifying reader variability. In the second aim, we will evaluate the potential improvement to the qualitative assessments of 2D CEUS when fused with the patient's pre-treatment cross-sectional imaging, which we hypothesize will provide better delineation of the initial tumor boundary. In the third aim, we will assess the potential added value of using multi-modality volumetric CEUS for detecting RCC recurrence post ablation and also an advanced Doppler non-contrast technique as an exploratory sub-aim. Finally, we will explore use of quantitative parameters extracted from 2D/3D CEUS exams to determine if this improves the overall performance of CEUS. At the study's conclusion, we hope to address the current limitations in RCC recurrence surveillance imaging with fully powered CEUS study to support clinical adoption, while also addressing prior limitations through the use of multi-modality and quantitative imaging.