Friedland Shai, Watson Drew, Pan Jennifer, Chen Yu, Nimgaonkar Ashish, Gulzar Zulfiqar, Atkins Alexander, Gupta Pratyush, Lucas Julian, Lai Jr-Ming, Hsieh Huangpin, Su Stephen, Gupta Samir, Sninsky John J, Mei Rui
Division of Gastroenterology, VA Palo Alto Health Care System, Palo Alto, California.
Biostatistics and Clinical Studies, CellMax Life, Sunnyvale, California.
Gastro Hep Adv. 2022 Feb 3;1(2):223-230. doi: 10.1016/j.gastha.2021.11.004. eCollection 2022.
There is a lack of convenient, sensitive, noninvasive strategies for screening and surveillance for colorectal neoplasia. An assay combining the results of circulating epithelial cells (CECs) and somatic mutations of cell-free DNA adjusting for age/sex using a unique algorithm is evaluated in patients requiring colonoscopy.
A prospective single-site 458-subject study (asymptomatic: 43% screening/43% surveillance, enriched with 65 symptomatic subjects undergoing colonoscopy) was conducted. The test analyzed CECs and somatic mutations. The probability of advanced neoplasia (advanced adenoma [AA] and CRCs) was determined by logistic regression methods adjusted for expected CRC incidence rate, prior history of AA, and patient age and sex on a training subset. A linear predictor was developed to generate a score scaled from 0 to 100. The test performance was evaluated on an independent set of subjects using prespecified algorithms and cut point.
Based on a predefined clinical threshold and predictive model derived from the training set (n = 232), analysis of an independent asymptomatic validation set (n = 194) yielded 89% (lower exact one-sided 95% confidence interval [CI]: 80%) specificity and 100% (95% CI: 37%)/78% (95% CI: 61%) sensitivity for detection of CRC/AA. In a secondary analysis, excluding surveillance subjects, the 97-subject screening cohort yielded 91% (95% CI: 79%) specificity and CRC/AA sensitivity at 100% (95% CI: 37%)/83% (95% CI: 56%, 87% for advanced neoplasia 95% CI: 64%). Significant associations ( < .0001) were detected between FirstSight scores and adenoma size, number, and ordinally increasing pathology classification.
A multimodal blood test that included CECs and somatic mutations with adjustment for age and sex demonstrated high sensitivity for the diagnosis of advanced colorectal neoplasia. The resulting score captures prognostic information for CRC progression of index adenoma size and number and has the potential to enable stratification of patients for screening or postpolypectomy surveillance colonoscopy.
目前缺乏用于结直肠肿瘤筛查和监测的便捷、灵敏、非侵入性策略。在需要进行结肠镜检查的患者中，对一种结合循环上皮细胞（CEC）结果和游离DNA体细胞突变，并使用独特算法根据年龄/性别进行调整的检测方法进行了评估。
开展了一项前瞻性单中心研究，纳入458名受试者（无症状者：43%为筛查/43%为监测，另外纳入65名接受结肠镜检查的有症状受试者）。该检测分析了CEC和体细胞突变。通过逻辑回归方法确定高级别肿瘤（高级别腺瘤[AA]和结直肠癌[CRC]）的概率，并在训练亚组中根据预期的CRC发病率、AA既往史以及患者年龄和性别进行调整。开发了一个线性预测指标以生成一个从0到100的评分。使用预先指定的算法和切点在一组独立的受试者中评估检测性能。
基于从训练集（n = 232）得出的预定义临床阈值和预测模型，对一个独立的无症状验证集（n = 194）进行分析，检测CRC/AA的特异性为89%（精确单侧95%置信区间[CI]下限：80%），敏感性为100%（95% CI：37%）/78%（95% CI：61%）。在一项二次分析中，排除监测受试者后，97名受试者的筛查队列的特异性为91%（95% CI：79%），检测CRC/AA的敏感性为100%（95% CI：37%）/83%（95% CI：56%，高级别肿瘤为87%，95% CI：64%）。在FirstSight评分与腺瘤大小、数量以及病理分级顺序增加之间检测到显著关联（P <.0001）。
一种包括CEC和体细胞突变并根据年龄和性别进行调整的多模式血液检测方法，对高级别结直肠肿瘤的诊断具有高敏感性。所得评分获取了指数腺瘤大小和数量的CRC进展的预后信息，并且有可能对患者进行分层，以确定其是否需要进行筛查或息肉切除术后监测结肠镜检查。
