الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
B-cell lymphomas, particularly diffuse large B-cell lymphoma (DLBCL), are prevalent among lymphoid malignancies, with DLBCL alone representing 17% of cases globally, equating to around 150,000 new cases annually. One subgroup of large B-cell lymphomas includes immune-privileged sites like primary central nervous system lymphoma (PCNSL), alongside others affecting areas like the vitreoretinal space and testes. Diagnosis of large B-cell lymphomas typically involves excision biopsy followed by various methods such as immunohistochemistry and molecular biomarker staining. Monitoring treatment response often relies on imaging techniques, which can carry risks and limitations, leading to interest in non-invasive methods like liquid biopsies, particularly circulating tumour DNA (ctDNA), for genetic information and disease monitoring. This study primarily focuses on PCNSL, aiming to identify common gene mutations, assess intra-tumour heterogeneity, and evaluate the utility of ctDNA in monitoring disease progression and treatment response. Samples from 36 patients in the UK TIER trial, investigating thiotepa-based regimens for relapsed or refractory PCNSL, were analysed using ddPCR and NGS technologies. Results showed varying treatment response rates and overall survival outcomes, with new thiotepa patients exhibiting better response rates compared to those who received it before. Mutational analysis revealed common mutations like MYD88, AFDN, and KMT2D, predominantly affecting key signaling pathways such as NFKB and immune signalling. Intra-tumour heterogeneity analysis highlighted diverse genetic profiles within tumours. Correlation analysis between ctDNA burden and clinical outcomes suggested associations with disease progression and survival, albeit without statistical significance. Fragmentation pattern analysis of ctDNA showed potential as an independent prognostic marker. In conclusion, ctDNA analysis, particularly using ddPCR, showed promise in detecting minimal residual disease and predicting clinical outcomes in PCNSL. Future research aims to validate these findings in larger cohorts and explore different NGS techniques for enhanced understanding.