The Need for a CYFRA 21-1 Cutoff Value to Predict Clinical Progression of IPF in Clinical Practice

To the Editor:

We read with much interest the article by Molyneaux and colleagues on the concentrations of CYFRA 21–1 in patients with idiopathic pulmonary fibrosis published online in your prestigious journal (1). The authors found that the serum concentration of CYFRA 21–1 is significantly higher in patients with idiopathic pulmonary fibrosis than in a healthy population and that it can predict disease progression and overall mortality in idiopathic pulmonary fibrosis patients, suggesting the potential usefulness of serum CYFRA 21–1 as a diagnostic and prognostic biomarker (1). Unfortunately, a specific cutoff value of CYFRA 21–1 was not defined in the study to use as a reference in clinical practice. Although the mean CYFRA 21–1 values were statistically different between healthy subjects and patients with idiopathic pulmonary fibrosis, most data from healthy subjects appear to overlap those from patients with idiopathic pulmonary fibrosis, making it difficult to determine a cutoff value for distinguishing both groups (1). The receiver operating characteristic curve analysis has been used in previous studies to define the most appropriate cutoff value of serum CYFRA 21–1 to differentiate benign from malignant disease, advanced from early cancer clinical stage, and squamous cell from small cell carcinoma (2, 3). Cutoffs of serum CYFRA 21–1 calculated from receiver operating characteristic curves were also useful for diagnosing preeclampsia and endometriosis and predicting response to therapy and prognosis in patients with cancer (3–6). These previous observations suggest that receiver operating characteristic curve analysis of serum CYFRA 21–1 concentration in subjects from the PROFILE (Prospective Observation of Fibrosis in the Lung Clinical Endpoints) study could also provide a cutoff value to diagnose the disease and predict clinical outcomes in idiopathic pulmonary fibrosis. We believe that if the authors can provide the cutoff value of serum CYFRA 21–1 for diagnosing and predicting clinical progression in idiopathic pulmonary fibrosis, it will facilitate the use of serum CYFRA 21–1 as a biomarker in the real-world clinical practice.