CancerMRD

• Tissue-informed approach detects tumor-specific mutations via WGS, analyzing both tumor and normal tissue. For this initial fingerprinting, a solid tumor sample and a blood sample (EDTA blood) is required.
• Subsequent MRD monitoring only requires liquid biopsy samples and uses existing fingerprint.
• Simple, non-invasive, and repeatable sampling provides the best conditions for longitudinal follow up testing and monitoring.
• With serial sampling, previous monitoring results are incorporated into the findings and depicted in a visual graph to illustrate progression.
• Using CancerMRD, a tumor content of 0,1% and lower can be detected in a liquid biopsy sample.
• Long-term monitoring tracks disease progression, which can be used for treatment-relevant decisions (such as adjuvant treatment or de-escalating treatment given continuously negative results) and early detection of a potential relapse for patients in remission.

In order to start monitoring, the initial fingerprint of the tumor is necessary, which requires the availability of a solid tumor sample. After the tumor-specific variants are detected by tumor vs normal tissue comparison, further tests require only blood samples (liquid biopsy). Sample reports of each step are included below.

This test is designed for MRD monitoring of solid tumor entities that shed ctDNA into the blood stream. It is not indicated for entities that have limited ctDNA shedding.

There are a few different approaches in MRD monitoring. Some use a so-called “tissue-naïve” approach, where the MRD monitoring is focused on common tumor alterations that are likely to be present in a given tumor entity rather than a personalized approach. Here at CeGaT, we are proceeding with a tissue-informed approach, where we initially sequence both tumor and normal tissue to detect tumor-specific mutations, providing a personalized tumor fingerprint.

Analysis through whole genome sequencing (WGS) allows for MRD detection on a much broader scale, identifying many more tumor-specific alterations than panel sequencing. These alterations have no relevance for treatment or prognosis, but including them in the fingerprint results in a much larger fingerprint size, and thus to higher sensitivity of MRD detection. In comparison to tissue-naïve approaches, the tissue-informed fingerprints contain patient-specific variations that are too rare to be included in generic fingerprints.

There are many ongoing studies to define uses of MRD in clinical setting for tumor patients. We consider the following points as the key applications of MRD monitoring.

MRD monitoring offers a dynamic assessment of tumor behavior at a molecular level, enabling real time monitoring of tumor burden and how the tumor is responding to ongoing treatment. This can provide insights into how much residual tumor DNA is present after surgery or treatment, guiding decisions on whether additional steps – such as changes in treatment regime, adjuvant treatment or de-escalation – should be considered.

For example, if MRD is detected after primary treatment, it may suggest incomplete response, leading clinicians to escalate treatment or opt for consolidation therapy to target remaining cancer cells. Conversely, the absence of MRD after treatment could support decisions to reduce or stop further treatment, potentially avoiding overtreatment and reducing side effects.

MRD detection can also guide the use of adjuvant therapies, such as chemotherapy or targeted therapies. MRD-positive patients may benefit from more intensive adjuvant treatment to minimize the risk of relapse, while MRD-negative patients might avoid unnecessary treatments.

MRD monitoring can detect the presence of residual tumor cells that may not be visible on imaging scans, even after a seemingly successful primary treatment. The presence of MRD may indicate the persistence of subclinical disease, suggesting that tumor progression is imminent.

MRD detection allows for the identification of patients at higher risk of relapse or progression. If MRD is detected in a patient after treatment, they may be more likely to experience recurrence. This information can help tailor continuous monitoring strategies to catch tumor progression in a timely manner.

Since MRD can detect circulating tumor DNA, relapse at a molecular level can be detected before it becomes clinically apparent. This is especially important in cancers where relapse can occur even after a prolonged period of remission.

Relapses can also be detected by imaging techniques (e.g., CT scans, MRIs) but these only detect growths of a certain size. Newly emerging symptoms can also indicate tumor relapse, usually appearing only with much larger growth. MRD, on the other hand, can identify very small amounts of residual tumor DNA in the bloodstream, enabling the detection of relapse at an earlier stage. This allows for timely interventions and adjustments in monitoring frequency, ultimately improving overall patient outcomes in case of relapse.