Dr. Javier Pascual
Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria University Hospitals, IBIMA, Malaga, Spain, on behalf of ESMO
Liquid biopsies that analyse circulating tumour DNA (ctDNA) can give more information on the spatial and temporal heterogeneity of a tumour than traditional tissue genotyping.
The use of liquid biopsy ctDNA assays in routine clinical practice requires careful attention to pre-analytical processing and the selection of the appropriate technology which may influence the results obtained.
ctDNA use for patients with cancer
The European Society for Medical Oncology (ESMO) Precision Medicine Working Group recently published new recommendations to guide medical oncologists on the clinical applications of this tool at all stages of the cancer care course. It aims to address the main technical aspects of testing and provide some quality standards required for assay reporting.
Liquid biopsies, and ctDNA detected in plasma, are rapidly developing a strong evidence base for use in patients with cancer, as their minimally invasive nature holds the potential of repeated sampling over time.
For patients with advanced cancer, for example, validated and adequately sensitive ctDNA assays are useful in identifying actionable mutations to direct targeted therapy. It may be used in routine clinical practice, especially in situations where tissue biopsies are suboptimal or time is crucial.
Answers to scientific questions
ctDNA release is believed to be proportional to tumour growth, with the fastest-growing tumour clones shedding the largest amount of DNA in plasma. Multiple technologies and modalities to detect, extract and quantify it are currently available, making a deep understanding of the analytical and clinical validity and utility of lab-developed or commercial ctDNA assays essential to address scientific and clinical questions.
It may be used in routine clinical practice, especially in situations where tissue biopsies are suboptimal or time is crucial.
The ESMO recommendations highlight the main aspects to consider before testing, when reading a report and then translating the findings into action in clinics, including some considerations on potential false negative or non-informative results, limitations for the detection of specific aberrations such as fusion and copy number events and tumour-specific recommendations.
Potential future applications
The new ESMO recommendations also provide insights on other possible applications of ctDNA in the future like identifying early-stage cancers and precancerous conditions in asymptomatic individuals to act in increasing cure rates. The recommendations also review its use for molecular residual disease assessment, molecular relapse monitoring and early assessment of treatment response in which evidence of utility is still lacking.