Serum KL-6 levels predict the occurrence and severity of treatment-related interstitial lung disease in lung cancer

This study aimed to investigate the feasibility of Krebs von den Lungen-6 (KL-6) as potential biomarker for treatment-related ILD (TR-ILD) in lung cancer. We recruited patients with lung cancer in whom serum KL-6 was measured for differentiating between pneumonia and ILD (category 1), diagnosing and assessing the severity of suspicious TR-ILD (category 2), or evaluating baseline levels before cancer treatment (category 3). Among 1297 patients who underwent KL-6 testing, 422 had lung cancer, and TR-ILD was detected in 194 patients. In lung cancer patients, median KL-6 level was higher in patients with drug-induced ILD than in those without ILD or those with radiation pneumonitis, and it was correlated with the severity of TR-ILD. Elevated serum KL-6 (cutoff: 449.9 U/mL) was an independent risk factor of severe TR-ILD, and elevated serum KL-6 with normal serum procalcitonin was associated with severe TR-ILD rather than non-ILD respiratory disease or non-severe TR-ILD. Patients with high serum KL-6 levels had worse overall survival compared with those with low serum KL-6 levels, regardless of patients’ categories. Therefore, serum KL-6 may be surrogate marker for predicting the occurrence and assessing the severity of TR-ILD at the time of suspicious ILD events and before lung cancer treatment.