Abstract 3747: Bronchial washing fluid sequencing is useful in the diagnosis of lung cancer with necrotic tumor

Abstract

Abstract Lung cancers identified with low-dose CT are typically early stage without endobronchial lesions, and most require a pathological diagnosis using invasive procedures. We conducted a study analyzing bronchial washing (BW) fluid using targeted panel sequencing to evaluate its diagnostic performance. And we aimed to elucidate the characteristics of patients group in which this method could be effectively applied. We prospectively enrolled patients with an incidental lung lesion suspected of early-stage lung cancer on chest CT and no visible endobronchial lesion on bronchoscopy from June 2017 to March 2018 at two independent hospitals. Lung cancer was histologically diagnosed using a diagnostic work-up including surgical lung biopsy, percutaneous needle biopsy, endobronchial ultrasound, and other biopsies. BW was performed on each patient in the subsegmental bronchus where the lung lesion was suspected to be located. Among shared genes between the panels for each cohort, we selected 8 genes that are frequently mutated known oncogenes/tumor suppressor genes in lung cancer not to consider passenger mutations for diagnosis. In addition, several filtering criteria were considered to differentiate cancer. Since criterion d considered definitive somatic mutations [known hotspot mutations or loss of function mutations with variant allele fraction (VAF) ≥ 2%] with criterion c (≥ 2 COSMIC11 variants with VAF ≥ 1%), the sensitivity was increased without loss of precision and the sensitivity of sequencing was higher than BW cytology. In total, 164 subjects (114 with lung cancer and 50 with benign) were enrolled. Of lung cancer patients, necrosis was observed on chest CT in 44 (38.6%) patients and malignant cells were identified upon BW cytological examination in 33 (28.9%) patients. Of total, 33 (20.1%) patients had complications related to invasive diagnostic test. By the panel with the criterion d, 42 patients (25.6%) were classified as cancer. The panel showed 100% of specificity, 100% of positive predictive value for diagnosing cancer whereas it had relatively low sensitivity. Twenty patients who were classified as cancer by sequencing despite of negative cytology. In the group with necrosis, the proportion of patients with positive for sequencing only was significantly higher than that of patients with positive for cytology only. In addition, the sensitivity of BW sequencing reached 75% in patients with necrotic tumors. The prevalence of necrotic tumors was significantly higher in SQC than in ADC. The significant proportion (66.7%) of primary tumors with positive for sequencing only and located in outer area had necrosis. This study demonstrated that BW sequencing could be applied for diagnosis in patients with necrotic lung lesion suspected of early-stage lung cancer in chest CT. It would be possible to reduce the frequency of unnecessary invasive procedures and subsequent complications. Citation Format: Jun Hyeok Lim, Hyun-Tae Shin, Sunmin Park, Woo Kyung Ryu, Lucia Kim, Kyung-Hee Lee, Sung Min Ko, Seung Jae Lee, Jung Soo Kim, Jeong-Seon Ryu. Bronchial washing fluid sequencing is useful in the diagnosis of lung cancer with necrotic tumor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3747.