Oncimmune Ltd, Nottingham City Hospital, Nottingham, UK;
J Thorac Dis. 2013 Oct;5(5):618-25. doi: 10.3978/j.issn.2072-1439.2013.08.65.
Further signal stratification for the EarlyCDT®-Lung test should facilitate interpretation of the test, leading to more precise interventions for particular patients.
Samples were measured for the presence of autoantibodies to seven tumor-associated antigens (TAAs) (p53, NY-ESO-1, CAGE, GBU4-5, SOX2, MAGE A4, and HuD). In addition to the current test cut-offs (determined using a previously reported Validation case-control sample set, set A; n=501), new high and low cut-offs were set in order to maximize the test's positive and negative predictive values (PPV and NPV, respectively). All three sets of cut-offs were applied to two confirmatory datasets: (I) the case-control set B (n=751), and (II) Population-derived set C (n=883), and all three datasets combined (n=2,135).
For the Validation dataset, cancer/non-cancer positivity for current cut-offs was 41%/9% (PPV =0.109, 1 in 9). The high positive stratum improved this to 25%/2% (PPV =0.274, 1 in 4). The low negative stratum improved this to 8%/23% (NPV =0.990, 1 in 105). This provides a 25-fold difference in lung cancer probability between the highest and lowest groups. The test performs equally well in subjects who fulfilled the entry risk criteria for the National Lung Screening Trial (NLST) and subjects who did not meet the NLST criteria.
The EarlyCDT®-Lung test has been converted to a four-stratum test by the addition of high and low sets of cut-offs: patients are thus stratified into four risk categories. This stratification will enable personalization of subsequent screening and treatment programs for high risk individuals or patients with lung nodules.
进一步对 EarlyCDT®-Lung 检测进行信号分层，有助于解读检测结果，从而为特定患者提供更精确的干预措施。
检测了 7 种肿瘤相关抗原（TAA）（p53、NY-ESO-1、CAGE、GBU4-5、SOX2、MAGE A4 和 HuD）的自身抗体。除了当前的检测截断值（使用之前报道的验证病例对照样本集 A 确定）之外，还设定了新的高、低截断值，以最大限度地提高检测的阳性和阴性预测值（PPV 和 NPV）。所有三组截断值均应用于两个确认数据集：（I）病例对照集 B（n=751）和（II）人群衍生集 C（n=883），以及所有三个数据集的组合（n=2135）。
对于验证数据集，当前截断值的癌症/非癌症阳性率为 41%/9%（PPV=0.109，9 人中 1 人）。高阳性分层将其提高至 25%/2%（PPV=0.274，4 人中 1 人）。低阴性分层将其提高至 8%/23%（NPV=0.990，105 人中 1 人）。这使得最高和最低两组之间的肺癌概率差异增加了 25 倍。该检测在符合国家肺癌筛查试验（NLST）纳入风险标准的受试者和不符合 NLST 标准的受试者中表现相同。
通过增加高、低截断值组，EarlyCDT®-Lung 检测已转换为四分层检测：因此，患者被分层为四个风险类别。这种分层将使高危个体或肺结节患者的后续筛查和治疗计划实现个体化。
