Project summary:

Within EXLIQUID, a nationwide liquid biopsy platform was established across all DKTK partner institutions and associated hospitals. More than 2,000 plasma and peripheral blood mononuclear cell samples from over 1,500 patients with advanced solid tumors have been collected and documented in the Clinical Communication Platform (CCP), creating a large decentralized liquid biopsy biobank in Germany. Based on this foundation, the consortium achieved major progress: a highly sensitive and specific ctDNA monitoring approach was developed and benchmarked, reaching sensitivity up to 99% at a variant allele frequency of 0.1% and specificity of 100%; oncogenic fragment detection in cfDNA was demonstrated using DNA methylation signals in breast and ovarian cancer and healthy donor samples; sarcomas were subclassified by cfDNA CNV and methylation patterns; a tissue-of-origin classifier for patients with cancer of unknown primary was developed; and serial ctDNA analyses revealed minimal residual disease detection down to 0.007% and dynamic changes early during treatment in thyroid cancer. Additional studies investigated cfDNA yield and metabolomic profiles in urological cancers, and baseline ctDNA analysis in precision oncology programs confirmed complementary value for therapeutic target identification. Together, these achievements highlight the translational impact of EXLIQUID.