The final results of a study of a blood test that can detect more than 50 types of cancer showed that it was accurate enough to be introduced as a multi-cancer screening test in people at higher risk for the disease, including those aged 50 and over get or older with no symptoms.

In an article published in the leading cancer journal Annals of Oncology[1] Today (Friday) researchers report that the test detected cancer accurately, often before any symptoms appeared, while showing a very low false positive rate. The test also predicted where the cancer was located in the body with great accuracy, which could help doctors choose more effective diagnostic tests.

GRAIL, Inc. (California, USA), the company that developed and funded the research, now has the multi-cancer screening test available in the US only by prescription and as a complement to other existing screening methods such as breast, cervical , Prostate, lung and colon cancer [2] . Screening tests aren’t available for many of the cancers the test can detect, such as: These include liver, pancreatic and esophageal cancers, which are among the deadliest and where early detection could make a real difference.

The first author of the article, Dr. Eric Klein, chairman of the Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, USA, said, “Finding cancer early, when treatment is likely to be more successful, is one of the most important ways we need to reduce the burden of cancer. These data suggest that the multi-cancer detection test, when used in conjunction with existing screening tests, could have a profound impact on how cancer is detected and ultimately on public health. ”

During the test, a blood sample is taken from each patient and analyzed for DNA, so-called cell-free DNA (cfDNA), which tumors (and other cells) release into the blood. Genome sequencing is used to detect chemical changes in DNA called “methylation” that control gene expression, and a classifier developed using machine learning (artificial intelligence) uses these results to detect abnormal methylation patterns that occur indicate the presence of cancer. In addition, the machine learning classifier can predict where the cancer is in the body. Results are available within ten working days from the time the sample reaches the laboratory.

The third and final sub-study of the Circulating Cell-Free Genome Atlas (CCGA) study published today examined the performance of the test in 2,823 people diagnosed with cancer and 1,254 people without cancer. He detected cancer signals from more than 50 different types of cancer and found that in all four cancer stages (I, II, III, IV) the test correctly detected when cancer was present (the sensitivity or the true positive in 51.5% of the cases Rate). Cases. The specificity of the test (the true negative rate) was 99.5%, which means that the test misdiagnosed cancer (the false positive rate) in only 0.5% of the cases.

The overall sensitivity of the test was 67.6% across stages I-III in 12 pre-specified cancers that account for two-thirds of cancer deaths in the US each year (anal, bladder, bowel, esophagus, stomach, head and neck, liver and bile duct -, lung, ovarian and pancreatic cancer, lymphoma and cancer of the white blood cells such as multiple myeloma) and totaled 40.7% in more than 50 cancers.

For all cancer types, detection improved with each cancer stage with a sensitivity rate of 16.8% in early stage I, 40.4% in stage II, 77% in stage III and 90.1% in stage IV – the most advanced stage, in which symptoms often occur.

The sensitivity varies depending on the type of cancer. For solid tumors with no screening options such as esophageal, liver and pancreatic cancer, the overall sensitivity of the test was twice that of solid tumors with screening options such as breast, colon, cervical and prostate cancer: 65.6% compared to 33.7%. The overall sensitivity in blood cancers such as lymphoma and myeloma was 55.1%.

In addition, 88.7% of the time, the multi-cancer screening test identified the tissue where the cancer was in the body.

Dr. Klein said, “We believe that cancers that release more cfDNA into the bloodstream are easier to spot. These cancers are also more likely to be fatal, and previous research shows this multi-cancer screening test is more likely to detect these cancers. Cancers like the prostate secrete less DNA than other tumors, which is why existing early detection tests for these cancers are still important. “

To understand how the test would fare in screening populations, the researchers estimated its positive predictive value (PPV) – the proportion of cases correctly identified as cancer, among those with a positive result – as well as its negative predictive value (NPV. ). ) – those correctly identified as not having cancer. The PPV was 44.4% among people 50 to 79 years of age who were most likely to develop cancer, and the NPV was 99.4%.

Dr. Klein concluded, “These data complement a growing literature supporting the use of next-generation sequencing for the detection of cell-free DNA in blood samples as a tool for the earlier detection of common cancers that make up significant numbers of cancers, deaths and other health problems worldwide. In addition, a screening test that only requires a simple blood draw could be an option for communities that do not have access to medical facilities. I am excited about the potential public health impact this approach will have. “

Researchers continue to collect additional data from the test in large, prospective studies in the US (STRIVE, PATHFINDER and REFLECTION studies) and the UK (SUMMIT study) and examine its feasibility for screening populations [3] . GRAIL has also partnered with the UK’s National Health Service to evaluate the clinical and economic performance of the multi-cancer screening test in approximately 165,000 eligible patients starting later this year.

One of the strengths of the CCGA study is that it includes a total of 15,254 participants from 142 clinics in North America, which helps ensure that the results can be generalized to a diverse population. Participants in this final sub-study were not included in the earlier stages of development of the test to ensure accurate performance assessments. Limitations of this sub-study include: taking blood samples from cancer patients after a biopsy could increase the amount of cfDNA in the blood compared to before the biopsy; CCGA is a case-control study and may not fully reflect how the test would perform under population screening conditions (this will be evaluated in the PATHFINDER study); and some inaccuracies have occurred in the detection of cancerous tissue in cancers caused by human papillomavirus (HPV) such as cancers of the cervix, anus, and head and neck.

Editor-in-chief of Annals of Oncology, Professor Fabrice André, Research Director at the Gustave Roussy Institute, Villejuif, France, said: “Cancer screening is the next step in cancer research as it could save millions of lives around the world. Developing technologies to address this problem is the first step. The next steps include developing new therapeutic interventions. At the same time, the major public awareness efforts must continue, or none of these efforts will change the results. “

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Remarks:

[1] “Clinical validation of a targeted methylation-based multi-cancer early detection test with an independent validation set”, by Eric Klein et al.Annals of Oncology. doi: https: //doi.Organization/10.1016 /j.annonc.2021.05.806

[2] The Multi-Cancer Detection Test is recommended for people over the age of 50 because more cancers are likely to develop by that time. It is available in the United States except New York state.

[3] ClinicalTrials.gov numbers: NCT03085888, NCT03934866, NCT04241796. The REFLECTION study does not yet have a number.

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