Risk-adapted modulation through de-intensification of cancer treatments: an ESMO classification
Authors: J. Pascual, G. Attard, F.-C. Bidard, N. Tarazona, T. Yoshino, N.C. Turner
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- Validated and sensitive ctDNA assays can be used to genotype advanced cancers and select patients for targeted therapies.
- Initial genotyping with ctDNA assays should be considered when rapid results are needed, and tissue is unavailable.
- ctDNA assay genotyping is limited by false-negative results, lower sensitivity for fusion events and copy number changes.
- Use of ctDNA to detect molecular residual disease is not recommended, due to lack of evidence of its clinical utility.
Circulating tumour DNA (ctDNA) assays conducted on plasma are rapidly developing a strong evidence base for use in patients with cancer. The European Society for Medical Oncology convened an expert working group to review the analytical and clinical validity and utility of ctDNA assays. For patients with advanced cancer, validated and adequately sensitive ctDNA assays have utility in identifying actionable mutations to direct targeted therapy, and may be used in routine clinical practice, provided the limitations of the assays are taken into account. Tissue-based testing remains the preferred test for many cancer patients, due to limitations of ctDNA assays detecting fusion events and copy number changes, although ctDNA assays may be routinely used when faster results will be clinically important, or when tissue biopsies are not possible or inappropriate. Reflex tumour testing should be considered following a non-informative ctDNA result, due to false-negative results with ctDNA testing. In patients treated for early-stage cancers, detection of molecular residual disease or molecular relapse, has high evidence of clinical validity in anticipating future relapse in many cancers. Molecular residual disease/molecular relapse detection cannot be recommended in routine clinical practice, as currently there is no evidence for clinical utility in directing treatment. Additional potential applications of ctDNA assays, under research development and not recommended for routine practice, include identifying patients not responding to therapy with early dynamic changes in ctDNA levels, monitoring therapy for the development of resistance mutations before clinical progression, and in screening asymptomatic people for cancer. Recommendations for reporting of results, future development of ctDNA assays and future clinical research are made.