Utilizing clinical features, genetic mutations, and a 14-gene molecular assay for optimizing the management of...

The increasing detection of multiple primary lung cancers (MPLCs) has outpaced the development of corresponding evidence-based management strategies. Current clinical practice remains constrained by two major limitations: (I) imperfect distinction between MPLC and intrapulmonary metastasis (IM) using imaging and pathology alone; and (II) the absence of standardized, lesion-level postoperative risk tools to guide adjuvant therapy and surveillance. To further optimize MPLC clinical management, we applied a 14-gene RNA-level molecular assay to examine its association with clinical factors and its potential to optimize clinical decision-making.

A total of 69 nodules from 30 patients were prospectively included for analysis. Patient demographic information, nodule characteristics, imaging features, histopathological characteristics, and mutation profiles obtained by next-generation sequencing (NGS) were collected for analysis. Additionally, all nodules were prospectively assessed for risk scores and stratifications with a 14-gene molecular assay. We performed correlation analyses between nodule-level risk stratification and the aforementioned clinical variables to evaluate the relationship between the 14-gene molecular assay-based risk assessment and conventional clinical factors.

We found that the majority of patients with MPLC were female and had a high frequency of a family history of cancer. Higher maximum diameter, computed tomography (CT) value, maximum standardized uptake value (SUVmax), and solid component on imaging were associated with greater invasiveness. Less invasive MPLC lesions more frequently harbored ERBB2 exon 20 insertions; however, with greater invasiveness, the mutation rate of EGFR increased and became the predominant mutation, while EGFR mutations did not appear to be associated with the long-term risk of lesions. A representative case is presented to illustrate the potential of the 14-gene molecular assay in assisting the differentiation of IM by identifying high-risk nodules. Additionally, the 14-gene molecular assay could serve as a novel independent dimension for assessing the risk of lesions postoperatively and aid in identifying lesions that require adjuvant therapy. Patients with all nodules classified as low risk demonstrated significantly improved disease-free survival (DFS) (P=0.04).

The 14-gene RNA expression assay may help prioritize high-risk lesions requiring clinical intervention, and provide guidance for postoperative adjuvant therapy and surveillance strategies, thereby optimizing treatment for MPLC.