Forero, Yency J.; Kammer, Michael N.; McGann, Kevin C.; Holmes, Hudson; Chen, Sheau-Chiann; Chen, Heidi; Argaw, Samson; Khalil, Timothy A.; Antic, Sanja L.; Zou, Yong; Zuo, Lianrui; Lasko, Thomas A.; Landman, Bennet A.; Deppen, Stephen A.; Grogan, Eric L.; Maldonado, Fabien. (2026).听.听PLOS ONE, 21(6), e0341522.听
This study investigated whether tracking changes over time in聽CYFRA 21-1, a聽serum biomarker聽(a substance measured in the liquid part of the blood) for聽non-small cell lung cancer (NSCLC), could improve the evaluation of聽pulmonary nodules聽(small growths or spots in the lungs). Most previous studies have relied on a single measurement of CYFRA 21-1, which may make it more difficult to distinguish cancerous nodules from benign (noncancerous) lung conditions. The researchers analyzed 132 patients with pulmonary nodules, with the primary analysis focusing on 121 patients who had not yet received treatment. CYFRA 21-1 levels were measured repeatedly over time to examine how they changed. At the start of the study, patients with malignant nodules had higher CYFRA 21-1 levels than those with benign nodules. Although the overall patterns of change over time were not significantly different between the two groups, malignant nodules showed greater variability and larger changes in CYFRA 21-1 levels over time. The researchers also found that a single baseline measurement of CYFRA 21-1 had moderate ability to distinguish malignant from benign nodules. The amount of change in CYFRA 21-1 over time also showed moderate diagnostic performance, with very high聽specificity(meaning it rarely identified benign nodules as cancer) but relatively low聽sensitivity聽(meaning it missed many cancers). Overall, the findings suggest that monitoring CYFRA 21-1 over time may provide additional information beyond a single measurement when evaluating pulmonary nodules. However, larger prospective studies are needed to confirm these findings before this approach can be used routinely in clinical practice.
Fig 1.听Receiver Operating Characteristic (ROC) curve for baseline CYFRA 21鈭�1 in the discrimination of benign versus untreated malignant pulmonary nodules.
The area under the curve (AUC) was 0.676 (95% CI: 0.565鈥�0.787). The diagonal grey line represents the reference line of no discrimination. The optimal Youden index threshold yielded a sensitivity of 0.633 and a specificity of 0.714.