Identifying Patients With High-Risk Stage I NSCLC Using a Tumor-Informed Plasma ctDNA Assay.

Area of Science:

• Oncology
• Molecular Diagnostics
• Cancer Genomics

Background:

• Early-stage non-small cell lung cancer (NSCLC) management is difficult due to high recurrence rates.
• Circulating tumor DNA (ctDNA) is a promising prognostic biomarker in cancer.
• Accurate prognostication is crucial for optimizing treatment strategies in NSCLC.

Purpose of the Study:

• To assess the clinical feasibility of plasma ctDNA analysis for prognostication in early-stage NSCLC.
• To determine the association between pre-operative ctDNA detection and recurrence-free survival (RFS).
• To evaluate ctDNA as a tool for informing treatment decisions in stage I NSCLC.

Main Methods:

• Prospective cohort study of 153 patients with clinical stage I NSCLC.
• Real-time plasma ctDNA testing using a tumor-informed whole exome sequencing approach (RaDaR™).
• Analysis of pre-operative and post-operative ctDNA levels and their correlation with RFS.

Main Results:

• Pre-operative ctDNA was detected in 22.4% of patients, with a median turnaround time of 6 weeks.
• Pre-operative ctDNA detection was significantly associated with shorter RFS (HR 3.81, p=0.006).
• Patients with pre-operative ctDNA had lower 2-year RFS (69.1%) compared to those without (84.2%).
• No post-operative ctDNA was detected in patients with pathologic stage I disease.
• Both preoperative ctDNA detection and tumor size independently predicted RFS in pathologic stage I NSCLC.

Conclusions:

• Plasma ctDNA analysis is clinically feasible for early-stage NSCLC.
• Pre-operative ctDNA detection is a significant independent predictor of recurrence in stage I NSCLC.
• ctDNA has the potential to guide treatment decisions and improve patient outcomes in NSCLC.