Exploring the clinical applicability of circulating tumor DNA in non-small cell lung cancer

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Lung cancer is a significant global health challenge, as it is the most commonly diagnosed cancer and the leading cause of cancer-related deaths worldwide. When lung cancer metastasizes, detailed molecular tumor profiling is crucial to provide patients with the most effective treatments. Currently, treatment decisions rely on testing tumor tissue, while monitoring treatment responses is done through radiological imaging. However, tumor tissue is often unavailable or insufficient for diagnostics, and imaging is frequently considered too insensitive to accurately assess treatment effectiveness. These limitations can lead to inadequate treatment for patients.

When cells die, they release their DNA into the bloodstream. In the case of cancer, tumor cells shed their DNA into the circulation, known as circulating tumor DNA (ctDNA). When detectable, ctDNA can serve as a valuable tool for diagnosing and monitoring cancer. Despite its potential, there remains uncertainty about how to incorporate ctDNA testing into diagnostics. To address this, Paul van der Leest investigated key factors influencing the clinical applicability of ctDNA testing in advanced non-small cell lung cancer (NSCLC).

His research demonstrated that variations in preanalytical workflows can lead to inconsistencies in molecular results. This is significant, as Dutch laboratories employ differing ctDNA workflows, potentially resulting in unequal patient care. Additionally, he provided evidence supporting the clinical relevance of ctDNA-based molecular testing for initial diagnosis, treatment response monitoring, and detecting resistance mutations in metastatic NSCLC patients. Overall, his thesis contributes valuable data to support the clinical implementation of ctDNA testing in the Netherlands.