All Cancers Lung Cancer Detection & Diagnosis

Minimal Residual Disease Assays – Detecting Circulating Tumor DNA

Medically Reviewed by Jonathan W. Riess, MD, MS

Written by J. GuanJan 2, 20246 min read

Source: Shutterstock

While companion diagnostics only examine specific driver mutations with corresponding FDA-approved targeted drugs, next-generation sequencing (NGS) has given rise to another group of more personalized liquid biopsies. These assays detect and measure any circulating tumor DNA (ctDNA) released into the bloodstream.

Circulating Tumor DNA — Depiction of ctDNA in the bloodstream. Adapted from: Shutterstock

A new concept of measuring any trace of residual cancer after cancer treatment is showing promise in predicting cancer progression. Minimal residual disease (MRD) assays harness the power of NGS to profile the changes in cancer DNA (or ctDNA) of different individuals. MRD assays can inform cancer recurrence early by matching the level of ctDNA before, during and after cancer treatment with the primary tumor sample. This may allow for timely re-treatment or planning of second-line treatment.

A positive MRD result (presence of ctDNA) may indicate

Little or no response to treatment
Occurrence of treatment resistance
Possibility of recurrence

With confirmation via conventional methods (radiography imaging and carcinoembryonic antigen serum markers), doctors can plan and discuss the potential subsequent treatment options.

A negative MRD result (absence of ctDNA) may indicate

Cancer remission after treatment
A lower risk of recurrence, though it is still possible

The liquid biopsy-based MRD assay is a brand-new concept that is still developing. It requires more uptake from patients and the medical community for more reliable results. Some MRD assays approved by the FDA and are already in use include:

Assay	Uses in lung cancer monitoring	Financial coverage
FoundationOne® Liquid CDx	Other than reporting companion-diagnostic associated findings (FDA-approved), it also provides MRD status in the form of blood tumor mutational burden (TMB) TMB is a measurement of somatic mutations in ctDNA. It is a potential predictive marker for immunotherapy response. Based on clinical evidence, an increased blood TMB is associated with higher sensitivity to immune checkpoint inhibitors.	Medicare covers it for advanced and relapsed cancer patients and those who seek further cancer treatment (after initial treatment). Several private insurers cover FDA-approved companion diagnostics
Guardant360 CDx	To assess response to immunotherapy (immune checkpoint inhibitor) for non-small cell lung cancer (NSCLC) patients It has not cleared FDA approval but is used as a laboratory-developed test regulated under the Clinical Laboratory Improvement Amendments (CLIA)	Covered by Medicare for all immunotherapy patients, regardless of tumor type Accepts payment by commercial insurance
Guardant Reveal	Started clinical trial in 2021 for predicting post-surgery NSCLC recurrence	Not available
Invitae Personalized Cancer Monitoring (PCM)	To detect residual ctDNA due to incomplete tumor cells removal after surgery To detect recurrence after chemotherapy (as adjuvant or systemic treatment) To be used in CLIA-certified labs only	Medicare coverage only eligible in several U.S. states Accept payment by commercial insurance

Key Takeaways

ctDNA-based MRD assays profile the entire tumor genome and then detect unique changes in DNA shed from the tumor into the bloodstream. This enables ongoing monitoring of cancer progression and recurrence using a minimally invasive biopsy technique (blood test).
The use of MRD assays for monitoring lung cancer status is still experimental. You can explore ClinicalTrials.gov to find ongoing clinical trials related to MRD assays for lung cancer.

Key Takeaways

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