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Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
Published on: June 8, 2019
Emerging Roles of Circulating Tumor DNA for Increased Precision and Personalization in Radiation Oncology
Noah Earland1, Kevin Chen2, Nicholas P Semenkovich3
1Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO; Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO.
Abstract:
Recent breakthroughs in circulating tumor DNA (ctDNA) technologies present a compelling opportunity to combine this emerging liquid biopsy approach with the field of radiogenomics, the study of how tumor genomics correlate with radiotherapy response and radiotoxicity. Canonically, ctDNA levels reflect metastatic tumor burden, although newer ultrasensitive technologies can be used after curative-intent radiotherapy of localized disease to assess ctDNA for minimal residual disease (MRD) detection or for post-treatment surveillance. Furthermore, several studies have demonstrated the potential utility of ctDNA analysis across various cancer types managed with radiotherapy or chemoradiotherapy, including sarcoma and cancers of the head and neck, lung, colon, rectum, bladder, and prostate . Additionally, because peripheral blood mononuclear cells are routinely collected alongside ctDNA to filter out mutations associated with clonal hematopoiesis, these cells are also available for single nucleotide polymorphism analysis and could potentially be used to detect patients at high risk for radiotoxicity. Lastly, future ctDNA assays will be utilized to better assess locoregional MRD in order to more precisely guide adjuvant radiotherapy after surgery in cases of localized disease, and guide ablative radiotherapy in cases of oligometastatic disease.
Insights
Circulating tumor DNA (ctDNA) analysis offers a promising liquid biopsy method for radiogenomics, aiding in minimal residual disease detection and surveillance after radiotherapy for various cancers.
Area of Science:
- Oncology
- Genomics
- Radiotherapy
Background:
- Circulating tumor DNA (ctDNA) analysis is an emerging liquid biopsy technique.
- Radiogenomics studies the correlation between tumor genomics, radiotherapy response, and radiotoxicity.
- ctDNA levels traditionally indicate metastatic tumor burden.
Purpose of the Study:
- To explore the integration of ctDNA analysis with radiogenomics.
- To investigate the utility of ctDNA for minimal residual disease (MRD) detection and post-treatment surveillance after radiotherapy.
- To assess the potential of ctDNA and associated blood cells in predicting radiotherapy outcomes and toxicity.
Main Methods:
- Review of recent breakthroughs in ctDNA technologies.
- Analysis of existing studies on ctDNA utility in various cancer types treated with radiotherapy or chemoradiotherapy.
- Examination of peripheral blood mononuclear cells for single nucleotide polymorphism analysis to predict radiotoxicity.
Main Results:
- Ultrasensitive ctDNA technologies can detect minimal residual disease (MRD) after curative-intent radiotherapy.
- ctDNA analysis shows potential utility across multiple cancer types (sarcoma, head and neck, lung, colon, rectum, bladder, prostate).
- Peripheral blood mononuclear cells may help identify patients at high risk for radiotoxicity.
Conclusions:
- Combining ctDNA liquid biopsy with radiogenomics presents a significant opportunity in cancer management.
- Future ctDNA assays could refine adjuvant and ablative radiotherapy strategies by assessing locoregional MRD.
- ctDNA holds promise for personalized radiotherapy approaches, improving treatment efficacy and reducing toxicity.

