Dr Chae on the Differences Between Tumor-Informed and Tissue-Agnostic Assays in NSCLC

"I don't think one is better than the other. I think both complement each other. So in my practice, I like to send both, so that I don't miss one or the other."

Young Kwang Chae, MD, MPH, MBA, a professor of medicine in the Division of Hematology and Oncology at Northwestern University Feinberg School of Medicine and co-director of developmental therapeutics at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, discussed the differences between tumor-informed and tissue-agnostic circulating tumor DNA (ctDNA) assays for molecular residual disease (MRD) detection, and how he uses the 2 approaches together for postsurgical surveillance in patients with lung cancer.

Tumor-informed assays are built from tumor tissue obtained at surgery or biopsy, Chae explained. That tissue is used to design a tumor-specific biomarker, which is then tracked in the blood; in his clinic, Chae said he runs this blood-based assay every 3 months as part of surveillance.

When tissue is unavailable or not needed, a tissue-agnostic approach, sometimes called plasma-informed testing, can be used instead, Chae noted. These assays rely on plasma alone, comparing cell-free DNA against the germline, known single-nucleotide polymorphism libraries, and clonal hematopoiesis of indeterminate potential algorithms to extract the DNA most likely shed by the tumor, he said.

Chae and colleagues have published real-world data comparing the 2 technologies in the postsurgical surveillance setting in lung cancer, finding that both assays were similarly effective at detecting MRD that was at least prognostic, he said. Chae noted that the study was not a therapeutic trial. Importantly, each assay detected cases the other missed, which is why neither can be considered definitively superior, he emphasized.

Tumor-informed testing does carry an advantage when tissue is available, Chae acknowledged. In practice, however, tissue is frequently depleted by the many immunohistochemistry markers run during the diagnostic workup, he explained, often leaving insufficient material for a tissue-based MRD assay.

"That's why we need to have [a] tissue-agnostic marker to complement that," Chae concluded.