Globally most cancers are detected at advanced stages with high treatment burden and low cure rates.

Noninvasive blood tests, or liquid biopsies, detecting the circulating DNA from cancers at early stages, when curative treatment is more likely to succeed, have been subject to intense research.

In a new prospective multi-center observational study,  development of a noninvasive cfDNA-based multi-cancer detection assay was assessed.

Results are reported at ASCO 2018.

Dr Eric Klein, lead author, from the Cleveland Clinic in Ohio, said “This is potentially the holy grail of cancer research, to find cancers that are currently hard to cure at an earlier stage when they are easier to cure, and we hope this test could save many lives. Most cancers are detected at a late stage, but this ‘liquid biopsy’ gives us the opportunity to find them months or years before someone would develop symptoms and be diagnosed.”

Simon Stevens, chief executive of NHS England, said "New techniques for precision early diagnosis would unlock enormous survival gains, as well as dramatic productivity benefits in the practice of medicine.”

1627 samples from 749 control patients (no cancer diagnosis) and 878 participants with newly diagnosed untreated cancer (20 tumor types, all stages) were analyzed in a preplanned substudy.

3 prototype sequencing assays were performed:

1. paired cfDNA and white blood cell (WBC, 60,000X) targeted sequencing (507 genes) for single nucleotide variants/indels;
2. paired cfDNA and WBC whole genome sequencing (WGS, 30X) for copy number variation;
3. cfDNA whole genome bisulfite sequencing (WGBS, 30X) for methylation.

For each assay a detection model was developed for all cancer pts; sensitivity was estimated at 95% specificity.

It was found that WGBS had the highest sensitivity. 

Detected cancers (stage I-III) included

• 28 colorectal (66% [48-84]),
• 19 esophageal (63% [38-84]),
• 5 head and neck (56% [21-86]),
• 5 hepatobiliary (80% [28-99]),
• 73 lung (59% [47-70]),
• 17 lymphoma (77% [50-93]),
• 11 multiple myeloma (73% [39-94]),
• 10 ovarian (90% [56-99])
• 10 pancreatic (80% [44-98]).

Breast cancer-specific assay results are reported separately in a second poster, due to be presented at ASCO soon.

Cancers with low signal ( < 10% sensitivity) include low gleason score prostate cancer, thyroid, uterine, melanoma, and renal cancers.

Comparison to tumour WGS and multi-assay classification will be reported in a separate study.