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Dynamic monitoring of circulating tumor DNA in non-Hodgkin lymphoma

Mark Roschewski, Louis M. Staudt and Wyndham H. Wilson

Abstract

Disease surveillance and response assessment in lymphoma relies on imaging by computerized tomography and positron emission tomography. Imaging scans, however, do not capture dynamic biologic processes at the molecular level and there is a need to more precisely direct treatment decisions. High-throughput next-generation sequencing-based assays detect circulating tumor DNA (ctDNA) in the blood allowing assessment of tumor dynamics and molecular heterogeneity at low thresholds. Monitoring ctDNA that encodes immunoglobulin receptors detects recurrent disease prior to scans in diffuse large B-cell lymphoma. "Liquid biopsies" of ctDNA for somatic mutations can also address tumor heterogeneity, clonal evolution, and mechanisms of resistance to guide precision treatment. To maximize clinical utility, pre-analytic collection and processing procedures need to be validated and standardized. In this Spotlight, we describe emerging clinical and research applications of ctDNA monitoring in lymphoma including real-time analysis of tumor dynamics, pre-clinical disease detection, and precision-directed treatment paradigms.

  • Submitted March 7, 2016.
  • Accepted April 12, 2016.