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

## TL;DR

This study shows that metagenomic sequencing can detect pathogens in febrile lung cancer patients when traditional tests fail, leading to faster fever resolution.

## Contribution

The study demonstrates that plasma mNGS improves diagnostic yield and guides antimicrobial therapy in febrile lung cancer patients.

## Key findings

- mNGS identified pathogens in 69.8% of CMT-negative febrile lung cancer patients.
- HSIF patients had higher defervescence rates at 48 and 96 hours with mNGS-guided therapy.
- Common pathogens detected included Epstein–Barr virus, Mycobacterium tuberculosis, and Candida albicans.

## Abstract

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.

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.

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.

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.