Sander Bach, MD, PhD, ​a research associate in the Department of Surgery at Amsterdam Universitair Medische Centra, discusses research examining circulating tumor (ct)DNA in colorectal cancer (CRC).

Patients with CRC who did not receive any form of treatment prior to the sampling of plasma used to detect ctDNA were enrolled in a systemic review. This was done because systemic therapy and surgical resection can influence the ctDNA profile, explains Bach. From there, various methods to detect ctDNA were examined, including DNA methylation such as hypermethylation, DNA mutations, and chromosomal copy number variations, which is more novel and has not been used in a formal review. Although these alterations have been known in the CRC space for a long time, there is not much literature about these types of aberrations in ctDNA, says Bach.

To understand the effectiveness of detecting these aberrations in the ctDNA, a lot of literature was examined for the review. In total, 8,478 abstracts were originally reviewed by investigators. At the final qualitative synthesis, 84 studies were included, allowing investigators to examine the sensitivity and specificity of ctDNA, concludes Bach.

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Sander Bach, MD, PhD, discusses research examining circulating tumor DNA in colorectal cancer.

Dr. Bach on Examining ctDNA in CRC 

Sander Bach, MD, PhD, ​a research associate in the Department of Surgery at Amsterdam Universitair Medische Centra, discusses ongoing research with circulating tumor DNA (ctDNA) in colorectal cancer (CRC).

There are numerous trials evaluating the utility of ctDNA in patients with CRC, says Bach, ​who adds that the Universitair Medische Centra laboratories are also conducting research in this space.

There was a lack of available literature regarding aberrations in ctDNA ​when initial research began, explains Bach. Ongoing clinical trials are now looking at ctDNA as a way to stratify patients for additional therapy.

​Although those results are starting to be presented, they have not yet demonstrated the power of ctDNA.

However, ctDNA appears to be advantageous in that less blood and DNA is required ​for testing. Additionally, ctDNA analysis appears to have higher sensitivity compared with methylation analysis, Bach concludes.

Sander Bach, MD, PhD, discusses ongoing research with circulating tumor DNA in colorectal cancer.

Dr. Bach Discusses Ongoing Research With ctDNA in CRC 

Sander Bach, MD, PhD, ​a research associate in the Department of Surgery at Amsterdam Universitair Medische Centra, discusses ​the results of a systematic review of circulating tumor DNA (ctDNA) in colorectal cancer (CRC).

the use of ctDNA and the hypermethylation analysis demonstrated significant evidence for early detection of CRC, says Bach. Septin 9 hypermethylation analysis appeared to be the most promising, demonstrating up to 90% sensitivity and high specificity.

Compared with methylation, ctDNA mutation analysis demonstrated lower detection rates, with ​sensitivities ofabout 50% or lower, explains Bach. ​

Although additional evidence is needed, ​copy number analysis seemed to be a successful detection method, says Bach. However, the majority of papers that used this method included patients who already underwent therapy, ​and thus had to be excluded from the review.

Sander Bach, MD, PhD, ​discusses ​the results of a systematic review of circulating tumor DNA in colorectal cancer.

Dr. Bach on the Results of a Systematic Review of ctDNA in CRC

Sander Bach, MD, PhD, ​a research associate in the Department of Surgery at Amsterdam Universitair Medische Centra, discusses the rationale to conduct a systematic review of circulating tumor DNA (ctDNA) in colorectal cancer (CRC).

Available literature on the role of ctDNA in CRC was thoroughly evaluated ​as part of the systematic review, says Bach. Ultimately, 3 objectives were identified that could utilize ctDNA as a way to improve patient outcomes.

The first objective had to do with the detection of CRC at an early stage, explains Bach. This is paramount because the earlier cancer is detected, the more likely that a ​patient's prognosis will be ​favorable.

The next goal of the review was to use ctDNA as prognostication to inform treatment selection, adds Bach. Not only is ctDNA important to determine which therapy a patient would derive benefit from, but also it would help to communicate what can be expected with certain therapies, explains Bach. 

The last objective was to use ctDNA in more advanced disease to help monitor patients after systemic chemotherapy or targeted therapies have been used, says Bach. Not only is this applicable in the advanced stage, but also after primary curative surgical resection; with ctDNA, minimal residual disease (MRD) could be detected, adds Bach. 

Notably, ctDNA is a noninvasive procedure that can detect MRD and potentially implicate additional therapies in a patient's treatment course, concludes Bach. 

Sander Bach, MD, PhD, ​discusses the rationale to conduct a systematic review of circulating tumor DNA in colorectal cancer.

Sander Bach, MD, PhD

Articles

Dr. Bach on Examining ctDNA in CRC

Dr. Bach Discusses Ongoing Research With ctDNA in CRC

Dr. Bach on the Results of a Systematic Review of ctDNA in CRC

Dr. Bach on the Rationale to Conduct a Systematic Review of ctDNA in CRC