Early prediction/detection of clinical response in metastatic NSCLC by improving liquid biopsy analysis

Non Small Cell Lung Cancer (NSCLC) patients are often treated with chemotherapy, which are toxic and can potentially lead to serious, even life-threatening side effects. Also, the quality of life can deteriorate. Unfortunately, not all patients respond to this treatment resulting in unnecessary treatment of these patients. Detecting the response at an early stage, preferably by a minimally or non-invasive alternative to tissue biopsies is therefore needed in order to avoid exposing patient to these harmful treatments. These responses to chemotherapy are currently evaluated by radiology, which is costly, asks for a dedicated radiologist and submits patients to radiation.

Therefore, the scientific goal of this project is to improve the sensitivity and reliability of liquid biopsy testing in NSCLC patients. We will accomplish this by investigating the most ideal pre-analytic conditions in urine samples in order to introduce this matrix in clinical setting. In addition, we will develop an assay to estimate the amount of contamination from cellular, non-tumor DNA in the cell-free DNA (cfDNA) fraction and to measure NSCLC tumor derived cfDNA present in the samples. These assays will contribute to a better understanding of the suitability of the samples for molecular analysis and will aid the detection of predictive biomarkers for the characterization of the patients’ tumor. The entire pre-analytical process and the developed assays will be validated in a group of NSCLC patients receiving chemotherapy. This will be tested in a small population of 10 patients as a first proof of concept and will be expanded to a larger multicentric population later on. In conclusion, with this project the early prediction/detection of response to treatment will become a possibility through the analysis of liquid biopsies.