Using Circulating Tumor DNA to Predict Cancer Recurrence and Guide Therapy

A recent technology is being increasingly used (at least in a research setting) to detect recurrence of cancer. The technology analyzes blood samples for tumor DNA circulating in the bloodstream, i.e. circulating tumor DNA (abbreviated ctDNA), sometimes called “liquid biopsy”.

Detection of circulating tumor DNA to predict recurrence has been previously demonstrated in breast cancer, colon cancer, and a subtype of lung cancer. Data on its use in identifying recurrence in bladder cancer was presented at the American Association for Cancer Research Annual Meeting in Chicago in early 2018. A similar study in colorectal cancer showed that circulating tumor DNA can detect recurrence of cancer more than 7 months ahead of any other method to detect recurrence.

How does this work?

The genetic testing company Natera has released a test under the brand name Signatera(TM). Samples of the patient’s original tumor are analyzed for specific DNA sequences that contain changes in the DNA (mutations) that are only found in the tumor and not in healthy cells. Therefore, this establishes a signature for the tumor that will be monitored for recurrence. To increase the accuracy of the results, the test focuses on at least 16 or more mutations in these detected DNA strands to discriminate between normal DNA and tumor DNA in the circulation. Hence, it decreases the chances of detecting’normal’ DNA strands in the circulation and falsely calling them cancer DNA, indicative of recurrence.

This test can be used in multiple ways in cancer management:

  1. It can be used to detect early cancer recurrence, possibly months before other modalities such as imaging technology can detect cancer recurrence
  2. It can be used to monitor response to treatment, i.e. the amount of circulating tumor DNA should decrease with administration of therapy
  3. It can help physicians decide which patients need additional therapy that may not be given in cases where there is no circulating tumor DNA present
  4. It can guide the choice of therapeutic regimens that may be targeted to the specific mutations that are detected in the circulation
  5. As more tests are performed and the knowledge of the roles of different mutations in guiding tumor behavior increases exponentially, these tests may have use in screening, i.e. detecting the initial tumors rather than just in the surveillance (follow up) phase after cancer therapy.

This blog article is based on a summary article published in Cancer Therapy Advisor on October 18, 2018.

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