Tumor specific DNA in bronchial lavage as a new diagnostic tool in lung cancer.

Abstract

3047 Background: A considerable fraction of lung cancer patients raise diagnostic challenges requiring invasive procedures with a certain risk of complications. Therefore, new diagnostic tools are of major interest. Aberrant methylation of the HOXA9 gene occurs in almost all malignant lung tumors and HOXA9 methylated DNA (meth-ctDNA) is shed into the circulation. The present study aimed at a prospective investigation of the possible diagnostic value of HOXA9 meth-ctDNA in bronchial lavage (BL). Methods: Patients enrolled were referred from the general practitioner suspecting lung cancer. The diagnostic package according to national guidelines includes chest and abdominal CT scan, bronchoscopy, relevant blood tests, and histopathological or cytological verification. Twelve ml liquid was collected at bronchoscopy for analysis of meth-ctDNA based on ddPCR technology according to our published method. The analysis was performed blinded to the clinical data and compared to the final diagnosis. Results: Eighty-nine patients were consecutively included from the 1 November 2018 to 31 January 2019. Fifty-six patients (62.9%) were diagnosed with lung cancer and 33 (37.1%) with a variety of benign diseases. Meth-ctDNA was found in 42/56 of the patients with a malignant tumor, sensitivity = 75.0% (95%CI=61.6-85.6%), whereas 31/33 of the patients without cancer were negative, specificity = 93.9% (95%CI= 79.8-99.3%). Table summarizes the results. The false negative samples were mainly from patients with peripheral tumors. The two false positive patients included one patient with Cryptogenic Organizing Pneumonia and one with unspecific nodule. Conclusions: The presence of meth-ctDNA in BL has a high sensitivity and specificity. If validated, the analysis represents a valuable adjunct in the diagnosis of lung cancer. Potentially, it could save the patients from numerous examinations with potential harmful risks and ensure a fast diagnosis. The relation between meth-ctDNA and final lung cancer diagnosis (N= 89). [Table: see text]