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

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 %.

Immunobiomarkers in small cell lung cancer: potential early cancer signals.

PURPOSE: We investigated the presence of autoantibodies as immunobiomarkers to a panel of tumor-associated antigens in a group of individuals with small cell lung cancer (SCLC), a disease group that has a poor overall cancer prognosis and therefore may benefit most from early diagnosis. EXPERIMENTAL DESIGN: Sera from 243 patients with confirmed SCLC and normal controls matched for age, sex, and smoking history were analyzed for the presence of these early immunobiomarkers (i.e., autoantibodies to p53, CAGE, NY-ESO-1, GBU4-5, Annexin I, SOX2, and Hu-D) by ELISA. RESULTS: Autoantibodies were seen to at least 1 of 6 antigens in 55% of all the SCLC patients' sera tested, with a specificity of 90% compared with controls. Using a higher assay cutoff to achieve a specificity of 99%, autoantibodies were still detectable in 42% of SCLC patients (receiver operator characteristic area under the curve = 0.76). There was no significant difference in sensitivity when analyzed by stage of the cancer or by patient age or gender. The frequency of autoantibodies to individual antigens varied, ranging from 4% for GBU4-5 to 35% for SOX2. Levels of Annexin I autoantibodies were not elevated in patients with SCLC. Antibodies were also detected in 4 separate patients whose sera were taken up to 3 months before tumor diagnosis. CONCLUSION: The presence of an autoantibody to one or more cancer-associated antigens may provide an important addition to the armamentarium available to the clinician to aid early detection of SCLC in high-risk individuals.