Editor Column: The Role of ctDNA in Guiding Adjuvant Therapy

stories May 21, 2020

ctDNA and Cancer

There are an estimated 33 million living survivors of cancer globally, and this number is expected to grow due to a rising cancer incidence in an aging population and improved survival following a cancer diagnosis. The current standard of care to monitor these patients for recurrences relies heavily on radiologic imaging alongside history and physical exams, tumor markers, and/or diagnostic procedures (e.g., colonoscopy). However, there is ambiguity in the specificity of these recommendations and the sensitivity of the tests as well.

The ability to predict cancer risk based off a single tube of patient blood continues to be an evasive dream to most practicing oncologists. However, with better understanding of the human genome and the advancement of genetic sequencing technology over the past decade, ctDNA has emerged as a new diagnostic modality and started to carve a niche for itself, specifically while monitoring for recurrences.

Plasma circulating tumor DNA (ctDNA) are short DNA fragments that originate from tumor cells but are freely circulating in the bloodstream. The mechanism of release into circulation is not well-understood, but a few hypotheses rooted in basic science suggest the role of tumor necrosis. As the tumor cells die, they undergo apoptosis wherein DNA is fragmented and extruded into the blood or lymph circulation.

The primary appeal of ctDNA is that it is non-invasive and can be tested using just 3 mL of a patient’s blood. An added benefit is the ability to detect extremely small quantities of genetic material, the presence of which can precede imaging findings by many months. And finally, sequencing genetic material allows us to assess for the presence of mutations in the cancer, which can sometimes help identify therapeutic targets.

On theMednet, we have seen conversations ranging from using ctDNA as a biomarker guiding therapy, to the identification of specific mutations which can be targeted with small molecular agents in lieu of traditional chemotherapy. Experts generally agree on the utility of ctDNA data in hematologic malignancies. Depending on the depth of sequencing specificity, it has established a role in monitoring for minimal residual disease (MRD). Use in solid tumor oncology is less established and many future studies are focused on expanding the use of this relatively non-invasive testing option as a surveillance and potentially a screening modality in the diagnosis of malignancies. Unanswered questions include the role of ctDNA clearance as a tool to guide termination of therapy- a biologically rooted concept, which on proof of principle can go a long way in improving the lives of many cancer survivors by limiting exposure to cytotoxic chemotherapy for extended periods of time.

Dr. Devika Rao

GI Associate Editor, theMednet

Role of ctDNA in surveillance:


Role of ctDNA in early stage cancer to guide adjuvant therapy:



Role of ctDNA in metastatic cancer treatment decisions:



Nadine Housri

Dr. Nadine Housri is the Co-founder and Chief Medical Officer of theMednet and an Associate Professor of Radiation Oncology at Yale.