Sam Klempner, MD, Discusses Minimal Residual Disease in Gastrointestinal Cancers


Sam Klempner, MD, spoke about the importance of expanding minimal residual disease platforms for patients with gastrointestinal cancers.

At the 2022 International Gastric Cancer Conference, Sam Klempner, MD, of Massachusetts General Hospital, spoke to CancerNetwork® about minimal residual disease (MRD) and how it’s used to inform the decision-making process when determining treatment for patients with gastrointestinal cancer.


The platforms to study minimal residual disease are continuing to evolve. I don’t think either of these may be the ultimate final say, but currently there are 2 broad categories. [With a tumor-informed approach], a patient’s tissue sample is subjected to broad sequencing often using whole-exome sequencing and then matched to a normal sample to filter out somatic mutations that are not from tumor cells and you use that sequencing data to predict clonal mutations. These are things that are going to be present in all of the tumor cells, and then you select variants and probe the blood for those variants. If you find them, you would call the assay positive and the person would be [considered to have positive] MRD. If you don’t, the test would be negative.

The other alternative is tumor uninformed or a tumor-naive approach. Ultimately the goal is the same, except you’re not using a tissue benchmark. In this case, you have a predetermined panel of genes and you probe the plasma, the cell-free DNA, for these genes along with a normal match to again filter out somatic alterations [that are] not from tumor cells. Then you come up with a list of potentially tumor-specific alterations and you probe the blood. Tumor-naive approaches often incorporate additional parameters such as methylated DNA detection to improve the sensitivity. Additional parameters are being explored and I suspect that both technologies will continue to improve in sensitivity and specificity over the coming months to years.

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