Understanding Minimal Residual Disease (MRD): A Guide to Some Helpful Calculations when Analyzing ctDNA
Minimal residual disease (MRD) detection through circulating tumor DNA (ctDNA) is gaining attention as a precise tool to measure residual cancer during and after treatment. Have you ever thought about what the MRD values mean?
Let’s break down how one could use MRD values to calculate estimations that might be more meaningful. We will be using a real-world example involving 33 ng of cfDNA extracted from 2 mL of plasma with an MRD of 0.0001. This discussion will try to calculate the result back to human genome equivalents (HGE)and cellular equivalents.
Human Genome Equivalents (HGE) per mL of Plasma
Human genome equivalents (HGE) represent how much cfDNA corresponds to the entire DNA content of a human cell. Each human cell contains approximately 6.6 picograms (pg) of DNA. We can calculate HGE using the following formula:
For 33 ng of cfDNA, we get 5000 genome equivalents. Since the cfDNA is extracted from 2 mL of plasma, the HGE per mL of plasma is 2500 HGE/mL plasma. This means that each mL of plasma contains DNA equivalent to approximately 2500 human cells.
Interpreting the MRD (ctDNA) Value
With an MRD value of 0.0001 (or 0.01% ctDNA), this indicates that 0.01% of the analyzed cfDNA is tumor-derived (ctDNA). To estimate how many tumor genome equivalents this represents per mL plasma:
This means there are about 0.25 tumor genome equivalents per mL of plasma, indicating a very low presence of ctDNA. In other words, this means that this would correspond to 0.25 tumor cells per mL of plasma (meaning you would need about 4 mL of plasma (or about 7.3 mL blood) to be able to find the equivalent of a single tumor cell (based on the MRD of 0.0001) assuming the tumor cell would be in circulation.
Note: Detecting ctDNA in plasma does not necessarily mean that the tumor is present in circulation. ctDNA can also derive from solid tumors, releasing ctDNA into the circulation.
Conclusion
Using this estimation and the real-world example, we have calculated that with 33 ng of cfDNA isolated from 2 mL of plasma and MRD of 0.0001, the value corresponds to about 0.25 tumor cells per mL of plasma (or 0.1375 tumor cells/mL blood).
At LIQOMICS, the limit of detection for MRD is about 5 x 10-6 (0.000005) for our validated tests. Can you estimate how much blood you would need to find the equivalent of one single cancer cell?
Ready to explore how our MRD test can enhance your diagnostic process? Schedule a consultation with our experts to discuss how our test can fit into your care strategy.
Author: Dr. Maximilian Schiener, Laboratory, Scientific and Quality Manager, Liqomics
