Preservation of cell‐free RNA in percutaneous core‐needle biopsy specimens' supernatants from non‐small cell lung cancer improves genomic testing performance

This prospective single-center study aimed to investigate whether preserving cell-free ribonucleic acid (cfRNA) in specimens' supernatants (SS) obtained from percutaneous core-needle biopsy (CNB) of non-small cell lung cancer (NSCLC) can improve the performance of genomic testing. Forty-three NSCLC patients who underwent image-guided CNB were enrolled. The SS from each CNB specimen was divided into two parts: one was mixed 1:1 with a cfRNA-protective solution, and the other was left unhandled. For quantitative analysis, 30 patients (regardless of mutation status) were evaluated by comparing cfRNA yield between cfRNA-protected and -unprotected SS. For qualitative analysis, 15 patients with fusion gene alterations were assessed by comparing genotyping results from cfRNA-protected SS to those from paired CNB specimens. Pneumothorax was the most frequent adverse event in CNB procedures, occurring in 20.9% of cases (9/43). No one experienced severe adverse events. In the quantitative analysis, 90.0% (27/30) of cfRNA-protected SS yielded adequate cfRNA, significantly higher than 53.3% (16/30) in cfRNA-unprotected SS (p < 0.01). In the qualitative analysis, despite ineffective cfRNA preservation in three cases, DNA-level mutations were still detected in both the CNB specimens and cfRNA-protected SS. The overall concordance of genotyping results between cfRNA-protected SS and paired CNB specimens was 100%, correctly identifying all ALK fusions, ROS1 rearrangements, and MET-14 skipping alterations. These findings highlight that preserving cfRNA in CNB-SS from NSCLC can improve the performance of genomic testing, particularly for RNA-based assays, without compromising the accuracy of DNA-based assays.