Circulating tumor DNA as a powerful tool in diagnostics and treatment outcome prediction - focus on large B-cell lymphomas and follicular lymphomas.

in Expert review of molecular diagnostics by Iva Hamova, Maria Maco, Anton Tkachenko, Kristyna Kupcova, Adriana Velasova, Marek Trneny, Heidi Mocikova, Ondrej Havranek

TLDR

  • The study reviews the concept of liquid biopsy and its application in detecting tumor-associated mutations in patients with large B-cell lymphomas and follicular lymphomas.

Abstract

Pathogenesis of large B-cell lymphomas (LBCL) and follicular lymphomas (FL) is a multistep process associated with development of diverse DNA alterations and consequent deregulation of critical cellular processes. Detection of tumor-associated mutations within non-tumor compartments (mainly plasma) is the basis of the 'liquid biopsy' concept. Apart from tumor mutational profiling, quantitative analysis of circulating tumor DNA (ctDNA) allows longitudinal assessment of tumor burden. ctDNA-based technologies provide a new tool for tumor diagnostics and treatment personalization. Our review provides a comprehensive overview and summary of available ctDNA studies in LBCL and FL. The accuracy of ctDNA based detection of lymphoma associated DNA alterations is correlated to the known LBCL and FL molecular landscape. Additionally, we summarized available evidence that supports and justifies the clinical use of ctDNA for lymphoma risk stratification, treatment response evaluation, and treatment response-adapted therapy. Lastly, we discuss other clinically important ctDNA applications: monitoring of lymphoma clonal evolution within resistance and/or relapse development and utilization of ctDNA for diagnostics in non-blood fluids and compartments (e.g. cerebrospinal fluid in primary CNS lymphomas). Despite certain challenges including methodological standardization, ctDNA holds promise to soon become an integral part of lymphoma diagnostics and treatment management.

Overview

  • The study reviews the concept of 'liquid biopsy' and its application in detecting tumor-associated mutations in blood plasma of patients with large B-cell lymphomas (LBCL) and follicular lymphomas (FL).
  • The accuracy of ctDNA-based detection of lymphoma-associated DNA alterations is correlated to the known LBCL and FL molecular landscape.
  • The study aims to summarize available evidence supporting the clinical use of ctDNA for lymphoma risk stratification, treatment response evaluation, and treatment response-adapted therapy.

Comparative Analysis & Findings

  • The study reviews available ctDNA studies in LBCL and FL, highlighting the accuracy of ctDNA-based detection of lymphoma-associated DNA alterations.
  • The findings support the clinical use of ctDNA for lymphoma risk stratification, treatment response evaluation, and treatment response-adapted therapy.
  • The study also discusses other clinically important ctDNA applications, including monitoring of lymphoma clonal evolution within resistance and/or relapse development and utilization of ctDNA for diagnostics in non-blood fluids and compartments.

Implications and Future Directions

  • The study suggests that ctDNA-based technologies hold promise to soon become an integral part of lymphoma diagnostics and treatment management.
  • Methodological standardization is a crucial challenge that needs to be addressed to further improve the accuracy and clinical relevance of ctDNA-based diagnostics.
  • Future studies should focus on developing more accurate and reliable ctDNA-based tests for clinical use, as well as exploring the potential of ctDNA for monitoring treatment response and disease progression.
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