WCLC 2025 - Posters & ePosters-P2.06.64 Fusion Transcript Burden Is Associated With Clinical Outcomes in Patients With Resected NSCLC

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This study investigates the role of Fusion Transcript Burden (FB)—the count of unique chimeric RNA transcripts—in resected non-small cell lung cancer (NSCLC) and its association with clinical outcomes, particularly regarding adjuvant therapy decisions.<br /><br />Background: Post-surgical disease-free survival (DFS) in NSCLC varies widely due to minimal residual disease (MRD), and there is a scarcity of biomarkers to guide adjuvant treatment. Fusion transcripts may represent tumors with high neoantigen loads and possibly indicate mechanisms of therapy resistance, such as extrachromosomal DNA (ecDNA) mediated evolution.<br /><br />Methods: Using RNA sequencing data aligned to GRCh37 with STAR and STAR-Fusion, fusion transcripts were identified in surgically resected Stage I-III NSCLC patients (both adenocarcinoma and squamous cell carcinoma) without neoadjuvant therapy or incomplete resections. The study excluded neuroendocrine and metastatic tumors. Clinical follow-up averaged 52 months.<br /><br />Results: Higher Fusion Burden was significantly associated with tumor progression across histologies. Fusion Burden differed significantly by AJCC stage, with Stage I and III showing distinct profiles. In Stage II and III squamous cell NSCLC patients receiving adjuvant therapy, high FB (≥10) correlated with improved 2-year DFS (p=0.043) and better 5-year overall survival (OS) (p=0.019). Conversely, no significant benefit was seen in low-FB patients or adenocarcinoma subtypes. Multivariate analysis indicated adjuvant therapy positively influenced survival in high FB patients but not in low FB groups.<br /><br />Conclusions: Fusion Burden emerges as a promising prognostic biomarker to identify NSCLC patients likely to benefit from adjuvant systemic therapy post-surgery, enabling improved personalization of treatment in early-stage disease with MRD. Ongoing research aims to refine the FB metric by integrating aberrant splicing patterns and protein-level validation, as well as exploring ecDNA-driven resistance mechanisms in high FB tumors.<br /><br />The Rush Cancer Center biorepository offers an extensive resource for further collaborations advancing biomarker-guided NSCLC management.

Asset Subtitle

Jeffrey Borgia

Meta Tag

Speaker Jeffrey Borgia

Topic Pathology and Biomarkers

Keywords

Fusion Transcript Burden

Non-Small Cell Lung Cancer

NSCLC

Adjuvant Therapy

Disease-Free Survival

Minimal Residual Disease

RNA Sequencing

Extrachromosomal DNA

Squamous Cell Carcinoma

Adenocarcinoma