Evaluating cell-free DNA-based blood tests for early detection of multiple cancers GrailBio DNA BloodTests Cancer CancerDetection
By Neha MathurNov 21 2022Reviewed by Aimee Molineux In a recent study published in Cancer Cell, researchers assessed several approaches for a circulating cell-free deoxyribonucleic acid -based multi-cancer early detection test. Defining the clinical limit of detection based on circulating tumor allele fraction enables the comparison of different approaches.
Recent modeling work predicted that adding an MCED test to standard care may improve early-stage detection and prevent 39% of all cancer-related deaths within five years of diagnosis. About the study A total of 2,800 participants, 1,628 with cancer and 1,172 without cancer, participated in the first circulating cell-free genome atlas substudy. The researchers randomly assigned 1,414 and 847 participants to independent training or validation sets and obtained samples that met prespecified laboratory quality control standards. Also, they ensured with cancer screening that they enrolled only those participants with cancer who had not begun their cancer therapy.
Cancer types might have dramatically different shedding rates even after controlling for the stage. Based on the distribution of tumor shedding across cancers, tumor biopsy sequencing could estimate cTAF across cancer types and their clinical stages. Likely due to increased tumor shedding in advanced-stage cancers, cTAF typically increases with the clinical stage.
Finally, the WG methylation was the most promising option in this study because, with ≈30 million CpGs, it was a pervasive signal across the genome. Of all cfDNA features assessed in this study, it was among the most sensitive methods for the following reasons:iii) had the highest cancer signal origin prediction accuracy.
The researchers used a methylation-based approach for further development because of its optimization potential and superior performance. Compared to WG methylation, the clinical LOD for the targeted methylation classifier validated in the second CCGA substudy showed nearly an order-of-magnitude improvement.
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