This manuscript reports an improved EarlyCDT-Lung panel with the addition of these two new AAb assays (i.e., MAGE A4 and HuD), and the removal of Annexin I, first in an optimization set comprised of patients with newly diagnosed lung cancer (before any treatment) and matched controls, and secondly in a prospective sample set confirming the additive value this modification brings to the original EarlyCDT-Lung panel in the clinical setting. Here, ANXA1 is linked to lung cancer.