Circulating Tumor DNA Testing and Clinical Decision-Making

The discussion turns to circulating tumor DNA (ctDNA) or plasma-based testing applications in clinical practice. Dr. Wistuba explains that liquid biopsy should be a multidisciplinary team decision, noting that most available technologies are DNA-based, making it difficult to obtain good RNA from blood. This creates the same limitations as tissue-based DNA testing, where rare mutations detectable only through RNA sequencing may be missed.

Dr. Rotow emphasizes that ctDNA represents a valuable tool when positive results are found, but negative results should be considered non-diagnostic rather than truly ruling out actionable alterations. This principle applies to all abnormalities detected in cell-free DNA testing, even EGFR mutations, due to sensitivity issues and tumor shedding variability. Dr. Wistuba confirms that if actionable alterations are found in liquid biopsy, clinicians can act upon them, but absence of findings does not exclude their presence in tissue.

Dr. Rodriguez addresses the practical question of allele fraction significance in ctDNA testing. She explains that ctDNA has made clinical practice more practical when tissue is insufficient or patients cannot undergo repeat biopsy procedures. The allele frequency does not matter when identifying actionable markers, as substantial data supports using this information for treatment selection, particularly for first-line treatment decisions that significantly impact patient outcomes. However, she notes that low tumor fraction in negative results can immediately indicate test insufficiency, requiring additional diagnostic approaches.

The panelists agree that accurate profiling at diagnosis remains crucial, as these are treatment decisions that matter from the first-line setting when initially meeting patients with advanced NSCLC.