Previously Funded Research

Tim Lautenschlaeger, MD

Indiana University

Research Project:

24-hour urine based ctDNA analysis for early stage NSCLC detection

Summary:

Imagine giving your doctor a urine sample to determine if you have lung cancer. Researchers at the Indiana University School of Medicine could make that idea a reality with a grant from the Lung Cancer Research Foundation. Urine samples from lung cancer patients and individuals at high risk of developing lung cancer will be tested for circulating tumor DNA, a form of DNA found only in cancer patients. While blood tests can be used to detect circulating tumor DNA, the amount in blood is too low for them to be useful in cancer screening. Urine has been shown to contain far larger amounts of circulating tumor DNA and is safer and easier to collect. If successful, this urine-based cancer screening test could make looking for lung cancer easier and encourage more people to get screened.

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Final report:
The study goals are to validate a urine ctDNA analytical approach, to determine the ctDNA detection rate using 24hr urine in comparison to blood-based analysis and to determine if 24hr urine analysis detects a greater variety of mutations than blood-based analysis. The first aim was the determination of the non-small cell lung cancer detection rate using 24-hour urine ctDNA analysis. Also, the researcher plans to determine the negative predictive value of the analytical approach using a separate cohort of high-risk individuals undergoing or qualifying for CT screening without cancer. All high-risk individuals will be followed for up to two years to verify the absence of cancer. The detection rate will be considered clinically useful if >90%. Aim 2 involves a comparison of the number of detected mutations using 24-hour urine-based vs. plasma-based ctDNA analysis in advanced non-small cell lung cancer. The plan is to determine the mutation quantification rate in patients with pathologically confirmed stage IV NSCLC. The researcher has samples for 15 early-stage NSCLC patient and is in the process of analyzing the samples. Matching tissue and blood are also being analyzed. Most of the time has been spent improving the analytical approach in a variety of ways. Supporting the central Aim 2 hypothesis, there were more mutations detected in 24-hour urine than in blood.

Impact:
ctDNA are fragments of tumor DNA that are released and end up in the bloodstream and urine. ctDNA is actively being studied to detect and monitor cancers. The quantity of ctDNA is higher in urine than in blood. It is much easier to collect large amounts of urine than blood. The researcher is in the process of refining and validating his analytic techniques. If successful, potentially this could be used as a tool to detect cancers at an earlier stage and could be an adjunct diagnostic test for cancer screening.