A sequencing pipeline that integrates a patient's specific tumor genetic data boosts the sensitivity of tests that detect cancer cell DNA circulating in the blood, according to a newly published study. The platform could routinely detect hard-to-spot circulating tumor DNA (ctDNA) on the order of one mutant molecule per 100,000 in plasma samples from 105 patients with various cancers. Although further work is needed, the test represents a stride in creating a ctDNA assay sensitive enough to be used in the clinic to monitor cancers. Most current tests for cancer patients are overly invasive or can fail to accurately track changes in tumors. Tests that seek out residual ctDNA in blood samples would be less invasive and would allow clinicians to better monitor tumors during treatment, potentially spotting relapses earlier. However, ctDNA can be hard to detect because it is sometimes present in only tiny amounts in blood, especially in people with small tumors or residual disease. Jonathan Wan and colleagues solved this issue with their Integration of VAriant Reads (INVAR) pipeline, a technique that analyzes hundreds of patient-specific mutations to better detect ctDNA. When tested with 176 plasma samples from 105 patients with melanoma, lung cancer, kidney cancer, or other types of tumors, INVAR quantified ctDNA to a degree of one mutant molecule per 100,000, and in one patient could detect ctDNA on the order of 2.5 parts per million. The technique also detected ctDNA in eight of 20 patients with melanoma that recurred after surgical removal. Wan et al. caution that INVAR will have to be applied with larger datasets to optimize its ability to detect residual ctDNA in patients with a high risk of cancer recurrence.
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Science Translational Medicine