Reducing the incidence of febrile neutropenia in cancer patients treated with chemotherapy with PointCheck: a portable non-invasive neutropenia analyzer

在美国，每年有65万名癌症患者接受化疗。作为一个副作用， 他们的中性粒细胞计数(帮助抵抗感染的白细胞数量)变得很低 (称为中性粒细胞减少症)，并使他们暴露在发热性中性粒细胞减少症(FN)中，这是发作性的 严重感染导致昂贵的住院治疗，有时甚至死亡。如果 早期发现中性粒细胞减少症，及时送货可避免FN 预防性抗生素或生长刺激因子。目前，中性粒细胞测量需要 参观医疗保健中心。这增加了感染风险(因为不经常进行测量 在随后的感染之前可能无法检测到低计数)，并降低化疗效果(如 为安全起见，化疗水平保持在频率和剂量的低端)。我们的目标是克服 这是PointCheck的局限性，PointCheck是一种非侵入性中性粒细胞检测，可在 当地卫生中心或家中，使医生能够最大限度地减少感染和 制定个性化的化疗计划。我们技术的基础是非侵入性光学成像 甲皱毛细血管微循环。我们在训练有素的地方进行了一项试点临床研究 护士使用PointCheck获取了46名化疗患者的数据。通过手动分析 一个训练数据集(来自16名患者的N=38个测量值)，我们建立了一个标记的流动间隙数据集 可以被认为是中性粒细胞代用品的微循环并展示了它们的数量 可用于区分基线患者(&gt；500个中性粒细胞/mm~3)和IV级中性粒细胞减少患者 (&lt；500/mm3)。然而，对人工分析的需要使得患者无法访问该技术 它的现状。在SBIR第一阶段的支持下，我们将(A)开发自动化的算法 在我们的训练集上采用的手动数据处理工作流，(B)在我们的 获得和未分析的测试数据库(N=来自30名患者的103次测量)和(C)生成 其他性能数据，包括更多中性粒细胞范围(500和1,500 中性粒细胞/mm3)，从而满足最低可行产品的要求。的连贯性 这些里程碑将在第二阶段启用在多站点诊断验证中使用PointCheck 试验证实，在临床条件下，这可以改善FN的管理 新的范例。

Every year in the US, 650,000 cancer patients are treated with chemotherapy. As a side effect, their neutrophil counts (number of white blood cells that aid in fighting infections) become low (referred to as neutropenia) and expose them to febrile neutropenia (FN) which are episodes of serious infection that entail costly hospitalization and sometimes death. If neutropenia is detected early, FN can be avoided through timely delivery of prophylactic antibiotics or growth stimulating factors. Currently, neutrophil measurements require visits to healthcare centers. This increases infection risk (as measurements are taken infrequently and low counts may not be detected before infections ensue) and reduces chemotherapy efficacy (as chemotherapy levels are kept at the lower end of frequency and dose for safety). We aim to overcome this limitation with PointCheck, a noninvasive neutrophil test that can be used frequently in local health centers or at home, enabling physicians to minimize infections and personalize chemotherapy planning. The basis for our technology is noninvasive optical imaging of microcirculation in nailfold capillaries. We conducted a pilot clinical study where trained nurses used PointCheck to acquire data from 46 chemotherapy patients. By manually analyzing a training dataset (N=38 measurements from 16 patients), we built a labeled dataset of flow gaps in the microcirculation that can be considered proxies of neutrophils and demonstrated their number can be used to distinguish baseline patients (>500 neutrophils/mm3) from grade IV neutropenic ones (<500/mm3). However, the need for manual analysis makes the technology inaccessible to patients on its current status. With support from SBIR Phase I, we will (a) develop algorithms that automatize the manual data processing workflow employed on our training set, (b) test those algorithms on our acquired and unanalyzed testing database (N=103 measurements from 30 patients) and (c) generate additional performance data including further intermediate neutrophil ranges (>500 and <1,500 neutrophils/mm3), thus fulfilling the requirements for a minimum viable product. The consecution of these milestones will enable, in Phase II, using PointCheck in a multi-site diagnostic validation trial to confirm, under clinical conditions, that the management of FN can be improved with this new paradigm.