The following article features coverage from the European Society for Medical Oncology (ESMO) 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

At a preset specificity of 99.4%, the overall sensitivity of a targeted bisulfite DNA sequencing assay for detecting the presence of cancer in circulating cell-free DNA samples of a subgroup of individuals with multiple types of cancer was 76%, according to results of a study presented at the European Society for Medical Oncology (ESMO) Congress 2019 held in Barcelona, Spain. 

Bisulfite sequencing, also known as methylation sequencing, involves bisulfite treatment of DNA prior to sequencing for the purpose of identifying methylated cytosine bases. Specifically, bisulfite converts unmethylated cytosine to uracil, but cannot react with methylated cytosine, thereby revealing the cytosine DNA methylation pattern. Because some alterations in the methylation pattern of DNA have been associated with inactivation of tumor suppressor genes or the induction of mutations, they represent an epigenetic mechanism through which cancer can develop. 

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Furthermore, because changes in the methylation pattern of DNA may represent an early event in the process of tumorigenesis, there is particular interest in using bisulfite sequencing of circulating cell-free DNA to screen individuals for cancer. 

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In this study, 3583 clinically annotated samples of circulating cell-free DNA from 1530 individuals with cancer and 2053 people without cancer  that were collected as part of 2 prospective, observational clinical trials ( Identifiers: NCT02889978; NCT03085888), were tested using a cross-validated targeted methylation sequencing assay. 

More than 20 different cancers were represented in the subgroup of patients with cancer, and 937 samples from patients with different stages of anorectal, hormone-receptor (HR)-negative breast, colorectal, esophageal, gallbladder, gastric, head and neck, hepatobiliary, lung, ovarian, and pancreatic cancers, as well as lymphoid leukemia, lymphoma, and multiple myeloma, were designated as the prespecified multicancer subset. 

At a preset specificity of 99.4% (ie, false-positive rate of 0.6%), the overall sensitivity of cancer detection in the prespecified multicancer subset was 76%, with lower sensitivity for early-stage versus later-stage disease (ie, 32% [stage I], 76% [stage II], 85% [stage III], 93% [stage IV]). 

When all samples from patients with cancer were evaluated, the overall sensitivity of the assay dropped to 55%.

Notably, when individual cancer types were considered, the sensitivities of the assay for detecting squamous cell (84%), and small cell lung cancer (83%) were higher compared with adenocarcinoma (58%). In addition, the assay was more sensitive in identifying HR-negative (66%) compared with HR-positive (20%) breast cancer. 

The precision of the assay for all samples — defined as the fraction of correct calls, including those from individuals without cancer — was 89%. Furthermore, the precision of the assay in localizing tissue of origin in the subset of samples from individuals with cancer was also 89%, with a similar finding across different stages of cancer.

In their concluding remarks, the study authors wrote that “these data support the feasibility of a single test that can screen for multiple cancers.”

Read more of Cancer Therapy Advisor‘s coverage of the ESMO annual meeting by visiting the conference page.


Oxnard GR, Klein EA, Seiden MV, et al. Simultaneous multi-cancer detection and tissue of origin (TOO) localization using targeted bisulfite sequencing of plasma cell-free DNA (cfDNA). Presented at: European Society for Medical Oncology (ESMO) Congress 2019; September 27-October 1, 2019: Barcelona, Spain. Abstract LBA77.