Blood test for faster and smarter detection of lung cancer
Esther Visser defended her thesis at the Department of Biomedical Engineering on April 10.

The challenge that doctors face in obtaining tissue biopsies from patients suspected of having lung cancer, especially when these patients are in poor condition, formed the basis of Esther Visser's research. The lack of a tissue biopsy can lead to delays in diagnosis and treatment, which complicates the care of these patients. Therefore, there is a need for a less invasive method, such as liquid biopsy (LBx), which can measure tumor markers in the blood and thus provide valuable information about the tumor. In her research, Visser is evaluating the clinical added value of LBx for the diagnosis of lung cancer, with the aim of improving diagnostic possibilities and optimizing the treatment of patients.
To this end, Visser investigated where and how LBx could potentially help in the clinic based on information from a large study involving approximately 1000 patients in various hospitals in the Netherlands. The diagnostic procedures in the current clinic for these patients were examined and several limitations were found. One example of a limitation is the possibility that multiple tissue biopsies are needed to make a diagnosis or determine the presence of genetic mutations. Both are necessary to determine the treatment strategy.
Various lines of research were investigated to find out whether the LBx model can be used for clinical application. First, the accuracy of a new mutation analysis method on ctDNA was determined by comparing it with conventional mutation analysis on tissue DNA (tDNA). It appeared that both methods could find overlapping mutations, but that ctDNA missed mutations that were found in tDNA. Therefore, a strategy was proposed in which ctDNA is performed first, which may result in more mutations being found and fewer tissue rebiopsies being necessary.
Next, a decision support model was developed to diagnose and subtype lung cancer based on LBx data. It was possible to confirm the presence and subtype of lung cancer for a subgroup of patients by using only information from blood. It was not possible to exclude lung cancer with LBx alone.
Finally, two minimally invasive sources of information were combined: radiology and LBx. Combining LBx and radiology led to an increase in the number of patients who could be identified with LC. Furthermore, we were able to sub-type patients by adding LBx, which was not possible with radiology alone. These results suggest that LBx can have added value in the clinic for the diagnosis of LC, possibly in cases where the current clinic cannot make a definitive diagnosis with tissue biopsies.
Determining treatment response of patients
In addition to the diagnostic phase, LBx can also be informative in determining the treatment response of patients. We have shown that LBx could predict the initial treatment response in a subgroup of patients, both in terms of response and disease progression. In addition, in some patients it was also possible to give an early indication that the patient will probably not benefit from the treatment for a long time (at least 6 months). These results suggest that LBx could also have added value in evaluating the response to treatment.
In conclusion, Visser's dissertation shows the potential of LBx to support clinical decisions regarding the diagnosis and treatment response of lung cancer patients. Before LBx can actually be applied in the clinic, further validation of the methods is needed, as well as a clear evaluation with clinicians on how LBx can possibly be implemented.
Title of PhD thesis: “From clinical data to decision support - Liquid biopsy for minimally invasive lung cancer diagnosis and treatment monitoring” (Under embargo)
Supervisors: (Catharina Hospital) and Federica Eduati.
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