Diagnostic value of metagenomic next-generation sequencing in patients with febrile lung cancer with negative conventional microbiological tests and without neutropenia

Introduction Fever in nonneutropenic lung cancer often remains microbiologically unresolved because of the limitations of conventional microbiological tests (CMT). We assessed whether plasma metagenomic next-generation sequencing (mNGS) improves diagnostic yield and accelerates defervescence in these patients. Methods We retrospectively analyzed 53 CMT-negative febrile lung cancer patients (August 2023–October 2024). Patients were classified into high-suspicion infectious fever (HSIF) or high-suspicion tumor fever (HSTF) groups based on mNGS results, and clinical management was adjusted accordingly. Results mNGS identified pathogens in 69.8% (37/53) of patients, commonly including Epstein–Barr virus , Mycobacterium tuberculosis , and Candida albicans . Patients in the HSIF group showed significantly higher baseline inflammatory markers than those in the HSTF group. Importantly, following mNGS-guided antimicrobial therapy, the HSIF group achieved significantly higher defervescence rates at 48 h (73.0% vs . 37.5%; p = 0.029) and 96 h (89.2% vs . 68.8%; p = 0.027) compared to the HSTF group. Discussion In conclusion, in CMT-negative, nonneutropenic febrile lung cancer, plasma mNGS significantly increases pathogen detection and informs antimicrobial decisions associated with earlier defervescence, although interpretation is limited by the retrospective design and lack of an independent gold standard.