“Liquid” biopsy finds cancer early in tissue of origin

New York (Reuters Health) -People suspected of having cancer before a histological diagnosis is made, and a blood test in development can detect the cancer and the tissue of origin, but there are few false positives, but many false positives. There is a negative.

This test uses next-generation sequencing technology to detect cancer-related DNA methylation patterns of cell-free DNA. It is developed by GRAIL, Inc., which funded the research.

Dr David Thiel, a urologist at Jacksonville, Mayo Clinic, Florida, presented the latest results from a test conducted on April 28 at a virtual meeting of the American Cancer Society (AACR).

He said many cancers are too late to be detected because of the presence of local or distant metastases at the time of diagnosis. “Detecting cancer before it develops metastatic disease can significantly improve 5-year survival,” Dr. Teal said at a media briefing.

For all cancers, 5-year cancer-specific survival is 89% for early diagnosis and 21% for late diagnosis, which may be the result of lead-time bias. For lung cancer, he said the 5-year cancer-specific survival rate was 56% for early diagnosis and 5% for late diagnosis. “Our idea is that a simple, non-invasive early cancer detection test may reduce cancer-related mortality,” Dr. Thiel said.

The GRAIL Early Cancer Detection Assay is currently being tested in several clinical trials.

At the AACR, Dr. Thiel presented data from a predesignated subgroup of the company’s Circulating Cell-Free Genome Atlas (CCGA). This is a multicenter, case-control observational study with a 5-year follow-up study of more than 15,000 adults. No diagnosis of cancer that provided a blood sample prior to clinical diagnosis.

In this analysis, those with a high clinical suspicion of cancer (HCS) were identified with clinically confirmed cancer (164 in the training set, 75 in the validation set) and non-cancer (49 in the validation set). Training and 15 validations). The clinically confirmed group in this HCS subgroup included people with multiple cancers from stages I to IV.

In the confirmed non-cancer group, all training and validation samples were correctly predicted as non-cancer (100% specificity), Dr. Thiel reported.

In the confirmed cancer group, cancer detection rates at all stages were 40.2% for training, 46.7% for validation, and 100% for specificity.

Excluding stage I renal cancer (overexpressed and poorly detected in the early stages) due to the low proportion of tumor cfDNA, the overall stage detection was 59.3%. Above Stage II, the detection rate was 78.9%, all with 100% specificity.

For detected cancers, tissue origin (TOO) was predicted in 93.9% of the training samples and 100% in validation. Of those with TOO results, accuracy was 85.5% for training and 97.1% for validation.

Dr. Thiel said the test could detect cancer and predict tissue of origin in people with a high suspicion of cancer before the pathological diagnosis is confirmed. It could be used to accelerate diagnostic workup in these patients. He also emphasized that the test is “intended to be used with the screening recommended by the guidelines, not a replacement for it.”

Population-scale studies are underway to validate test performance.

Regarding the results, Dr. Antonio Rivas of AACR said: “This is one of the fastest-growing areas of cancer research in the clinic. This summary presents data for more than 15,000 suspected cancers, and blood tests show that Not only did we know and couldn’t confirm the presence of cancer, but we also knew where the cancer was and many of these cancers before they could be diagnosed by other means. ”

“We are looking at the future in real time. This session (at the AACR) saw big data (display) that these assays should be broadly applicable with the appropriate regulatory approval. Sometimes it will be remembered, it won’t take long and it will change our practice, “said Dr. Rivas of the University of California, Los Angeles.

This study was funded by GRAIL, Inc. Some authors have a financial relationship with the company. Source: 2020 American Cancer Society, announced April 28, 2020