Circulating tumor DNA (ctDNA), small pieces of DNA released from dying tumor cells into the bloodstream, can be easily and non-invasively identified and examined through a simple blood test. This method allows doctors to measure the amount of ctDNA in a patient’s blood and detect mutations, providing valuable information about the genetic changes in the remaining live tumor cells. The use of ctDNA as a diagnostic tool for certain cancers, including pancreatic malignancies, is promising, as it can aid in treatment planning and monitoring the effectiveness of the treatment on an individual patient level.
Pancreaticobiliary cancers, malignancies that develop in the pancreas and biliary tree, have limited treatment options and carry a very poor prognosis. Next-generation sequencing (NGS), a technique that identifies the order of nucleotides in DNA fragments, can help find mutations in the genetic code. In certain cancers, including subsets of pancreaticobiliary cancers, NGS can identify changes in DNA that can inform treatment decisions when finding drug-targetable mutations. However, because these methods require tumor tissue, quite a bit of room for error and complications exist due to challenges with obtaining biopsies that represent the tumor optimally.
A team of researchers conducted a clinical trial to determine if ctDNA, which healthcare professionals can obtain more easily, cheaply, and less invasively than tissue for NGS, could help estimate treatment response. The results of the study, recently published in JAMA Network demonstrate the practicality of ctDNA analysis as it could provide a feasible alternative to NGS for screening pancreaticobiliary cancer patients.
The study, which included patients with pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma (CC), compared ctDNA testing and tissue NGS testing. The researchers evaluated mutation concordance (mCR) rates, which measure how many genetic mutations are identified by both tests.
The study evaluated a total of 570 patients, 570 with PDAC and 220 with CC. For PDAC, 130 patients underwent both testing procedures, and 65.4% showed shared gene alterations between ctDNA and tissue testing. Similarly, for CC, 48 patients had both tests, and 66.7% exhibited shared mutations between the tests. Further analysis showed a statistically significant mCR, indicating that the ctDNA and tissue NSG identify mutations similarly.
In addition, the researchers identified some markers associated with more progressive disease. In PDAC patients, increased ctDNA levels of two genes, TP52 and KRAS, predicted a greater chance of progressive cancer.
The study's findings underscore the significance of ctDNA testing as a viable alternative to tissue NGS testing for pancreaticobiliary cancers. The substantial mCR rate between the two methods supports the potential of ctDNA testing in these settings, marking a significant advancement in cancer diagnosis and treatment planning.
Sources: Gastroenterol Res Pract, JAMA Netw