EarlyCDT®-Lung test: improved clinical utility through additional autoantibody assays

Abstract

Tumor-associated autoantibodies (AAbs) have been described in patients with lung cancer, and the EarlyCDT®-Lung test that measures such AAbs is available as an aid for the early detection of lung cancer in high-risk populations. Improvements in specificity would improve its cost-effectiveness, as well as reduce anxiety associated with false positive tests. Samples from 235 patients with newly diagnosed lung cancer and matched controls were measured for the presence of AAbs to a panel of six (p53, NY-ESO-1, CAGE, GBU4-5, Annexin I, and SOX2) or seven (p53, NY-ESO-1, CAGE, GBU4-5, SOX2, HuD, and MAGE A4) antigens. Data were assessed in relation to cancer type and stage. The sensitivity and specificity of these two panels were also compared in two prospective consecutive series of 776 and 836 individuals at an increased risk of developing lung cancer. The six-AAb panel gave a sensitivity of 39 % with a specificity of 89 %, while the seven-AAb panel gave a sensitivity of 41 % with a specificity of 91 % which, once adjusted for occult cancers in the population, resulted in a specificity of 93 %. Analysis of these AAb assays in the at-risk population confirmed that the seven-AAb panel resulted in a significant increase in the specificity of the test from 82 to 90 %, with no significant change in sensitivity. The change from a six- to a seven-AAb assay can improve the specificity of the test and would result in a PPV of 1 in 8 and an overall accuracy of 92 %.

Tumor-Associated Autoantibodies: Re-Optimization of EarlyCDT-Lung Diagnostic Performance and Its Application to Indeterminate Pulmonary Nodules

“…The performance characteristics have been further validated in the commercial setting by an audit of clinical outcomes for the first 1599 patients who had a valid EarlyCDT-Lung and unknown nodule status [14]. The test consistently identifies lung cancer with 92% accuracy (compared with 50% for CT) with a sensitivity (true positive rate) of ~40% for all stages and types (small cell and non-small cell) of lung tumors and a specificity (true negative rate) of ~93% for all cohorts, showing the robustness and reproducibility of this assay system [12].…”

“…This cohort has been described elsewhere and was previously used to set the current commercial cut-offs for EarlyCDT-Lung [12]. Briefly, serum samples from 235 patients with lung cancer obtained at or just after histopathological confirmation of the tumor, were assayed.…”

“…detects the presence of TA autoantibodies to a panel of seven lung cancer associated antigens using an indirect enzyme-linked immunosorbent assay (ELISA) method [10] [11]. A sample is positive when at least one of the panel of TA autoantibodies is elevated above a pre-determined cut-off [12]. The test has been both technically [10] and clinically validated in seven independent validation cohorts [11] [13] including highrisk control groups matched for age, sex, and smoking history.…”

“…So the purpose of this present paper is largely technical, and describes the creation and use of a receiver-operating characteristic (ROC) curve for EarlyCDT-Lung. Because of the need for a relatively large number of cancers to achieve this, a case-control cohort (designated the optimization cohort) previously used for validation of EarlyCDT-Lung was used [11] [12]. It was compared with a dataset (designated the nodule cohort) derived from our commercial operations (designated the audit cohort).…”

Survivin Autoantibodies Are Not Elevated in Lung Cancer When Assayed Controlling for Specificity and Smoking Status

“…During tumor development, tumor-antigen expression elicits cellular and humoral immune responses (2)(3)(4). Identifying autoantibodies to tumor-associated antigens (TAA) is thought to be a promising method of early lung cancer diagnosis (5)(6)(7)(8), especially because these autoantibodies have been found up to 5 years before CT detection (9,10).…”