In this project (cooperation between Freiburg University and Stanford University), circulating tumor DNA (ctDNA) have been established in the cerebrospinal fluid (CSF) and blood plasma of patients with brain lymphomas as a clinically useful biomarker. Brain lymphomas are often difficult to diagnose, and the response to treatment varies widely and is difficult to predict.
There are currently no biomarkers that help with these challenges. The project group has optimized an ultra-sensitive next-generation sequencing method that helps to detect minute amounts of ctDNA in body fluids and establish ctDNA as an MRD and diagnostic marker. They examined a total of 306 samples from 136 patients, including 92 with brain lymphoma and 44 with other brain tumors. At diagnosis, the group was able to detect ctDNA in 78% of plasma samples and 100% of CSF samples. In addition, they were able to show that the detection of ctDNA in blood plasma in treatment-naïve settings and during immunotherapy allows the prediction of treatment response and clinical outcomes.
Furthermore, the researchers trained a machine learning method on mutation data from more than 2,600 brain tumor patients that facilitates noninvasive differentiation between brain lymphomas and non-brain lymphomas based on the mutation pattern of ctDNA in CSF and blood plasma. An independent validation cohort showed that brain lymphoma classification is successful in 60% of cases based on CSF-ctDNA, with a specificity of 100%.
In summary, they have shown for the first time that ctDNA can be used as a useful biomarker in patients with brain lymphomas, contributing to biopsy-free diagnosis from CSF and as a sensitive MRD marker from blood plasma to predict clinical outcomes.
Mutter JA*, Alig S*, Esfahani MS, Lauer EM, Mitschke J, Kurtz DM, Kühn J, Bleul S, Olsen M, Liu CL, Jin MC, Macaulay CW, Neidert N, Volk T, Eisenblaetter M, Rauer S, Heiland DH, Finke J, Duyster J, Wehrle J, Prinz M, Illerhaus G, Reinacher PC, Schorb E, Diehn M, Alizadeh AA, and Scherer F.
Journal of Clinical Oncology. 41, no. 9 (March 20, 2023) 1684-1694. DOI: 10.1200/JCO.22.00826
* Equal contribution
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