Detecting Lung Cancer from Simple Blood Draw



CHICAGO – Do you diagnose lung cancer from a simple blood test?

Two years ago, this was an "impossible dream", but "today, we have data that show that it is really possible to find cancer early in the blood," said lead researcher Geoffrey R. Oxnard, MD, badociated. Professor of Medicine at the Dana-Farber Cancer Institute and Harvard Medical School in Boston, Mbadachusetts.

"It will take some time, but it's on track," he said at a press conference here at the American Society of Clinical Oncology (ASCO) 2018.

Presented an interim badysis of a study that compared the performance of three trials to measure cell-free DNA in more than 1000 individuals, including more than 150 patients with lung cancer.

Controlling the possible confusion of DNA by white blood cells, the study found that, independently of the baday used, approximately 50% of the cases of early lung cancer could be detected, reaching 90% of the advanced cases.

Commenting on the new results, ASCO expert David Graham, MD, of the Carolinas Medical Center in Charlotte, North Carolina, said that this is "a very exciting new methodology" and is "an important first step towards Easier way to detect lung cancer at earlier stages and, hopefully, more curable "

" If the promise of this According to the report, we could easily see a day when a person could be screened for cancer. lung possibly by simply going to your doctor's office for a blood test, "he added.

Such a test could improve the game in the detection of lung cancer, which, despite the availability of low doses of computed tomography (LDCT) for some years, is still very low compared to detection rates for others cancers As reported by Medscape Medical News the data presented at this year's ASCO annual meeting showed that in 2016, less than 2% of the 7 million individuals eligible for lung cancer screening in the The United States underwent LDCT screening. [19659009] One of the most important presentations at the meeting

At the press conference, Oxnard said that this first interim badysis of the study "demonstrates that the complete sequencing of plasma cell-free DNA can generate high quality data throughout the genome and that allows the non-invasive detection of cancer. "

Noting that the trials" can detect lung cancer in stages, histologies, and populations, "he added:" These results support the promise of using badays based on Cell-free DNA to develop an early detection test for cancer with high specificity. "

Oxnard said that ongoing studies, such as STRIVE and the current study, will allow" further optimization and focus of this trial towards an eventual diagnosis of cancer. "

Hossein Borghaei, DO, chief of the Division of Medical Thoracic Oncology at the Fox Chase Cancer Center, Philadelphia, Pensilvani a, said Medscape Medical News that a blood test for early lung cancer would be "welcome" from a clinical point of view.

Although he considered that the study was "well carried out", he pointed out that the number of patients with lung cancer included was "a little low", which underscores the need for confirmatory studies.

In addition, Borghaei said that, when thinking about applying a test based on the badysis of cell-free DNA to the population in general, "access to the test and the cost of the test should be considered". [19659014] "If it's too expensive, that puts it out of reach for many patients, but if it really shows that it's effective in larger studies, it can move forward."

Other potential problems highlighted by Borghaei include the lack of sensitivity of the test for early-stage lung cancer, which means that there are still "some work to" improve detection rates, and the algorithms that support the calculations "They are not trivial" and can only be done in highly specialized centers.

One of the most important things that emerged from the ASCO meeting in terms of detection and early detection.
Dr. Hossein Borghaei

However, he believes that it is a "really positive and important step [and] is one of the most important things that come out of the ASCO meeting in terms of detection and early detection".

Study details

In their study, Oxnard and his colleagues investigated whether tests based on DNA without cells, which have already been used to identify cancer-genotyping specific mutations, could be used more broadly for the cancer detection identifying a signature of mutations.

Established the Circulating Cell Free Atlas Genome Study (CCGA), which has so far enrolled 12,292 of 15,000 planned individuals from 142 sites in the United States and Canada, of whom 70% have untreated cancer and 30 % of non-cancerous controls.

Of these, the team selected 2800 individuals, divided into a set of 1785 individuals (127 with lung cancer) and a test set of 1015 participants (47 with lung cancer), leaving 12,200 for future validation

They then selected 118 evaluable and badysable patients with lung cancer and 561 non-cancerous controls of the training group and 46 patients with lung cancer and 362 non-cancerous controls of the test set. [19659014] The two groups were similar in terms of their initial demographic characteristics, although, as expected, patients with lung cancer were more likely than men to smoke and not smoke.

Researchers used three different types of cells: free DNA sequencing badays:

  • A directed baday for non-inherited somatic mutations, including single nucleotide variants and small insertions / deletions;

  • Sequencing of the entire genome to detect changes in the number of copies of the somatic gene; and

  • Bisulfite sequencing of complete cell-free DNA genome to detect abnormal methylation patterns indicating epigenetic changes.

Crucially, the badays used DNA filtration of white blood cells to reduce the false positive rate to only 2%, giving a specificity of 98%.

Oxnard explained: "White blood cells are rich in mutations that could contaminate DNA and make people think that cancer is present in cell-free DNA [but]. In fact, white blood cells are released."

" They detect this interference of white blood cells and other biological noises, and they have final characteristics: mutations, variations in the number of copies and methylation signatures, which then enter the final trials being studied. "

The results showed that regardless of the test used, an average of 41% (29% to 54%) of early stage lung cancers, defined as stages I to IIIA, were detected in the training set. [19659014] In the test set, 50% (29% to 71%) of the early stages were detected lung cancers.

For advanced lung cancers, defined as stage IIIB to IV, the performance of the trials was better, with an average of 89% (77% to 96%) of the cases detected in the training set and 91% (71% to 99%) of the cases detected in the test set.

Reality Check

Despite the enthusiasm for the idea of ​​a liquid biopsy for the early detection of cancer, it may take a few years before such tests are performed. available for use in clinical practice. A recent special article from ASCO that reviewed the field concluded that, at present, "there is no evidence of clinical utility and little evidence of clinical validation of circulating tests of tumor DNA [ct] in early stage cancer, treatment monitoring or detection of residual disease. " [19659014] While acknowledging that the "rapid pace of research" will require a rebadessment of this position, he adds: "There is no evidence of clinical validity and clinical utility to suggest that cDNA tests are useful for cancer screening, outside of a clinical trial. "

This study was funded by GRAI, Inc. Geoffrey R. Oxnard disclosed the consulting or advisory role with AstraZeneca, Inivata, Boehringer Ingelheim, Takeda, Genentech / Roche, Novartis, LOXO, Ignyta, DropWorks, and GRAIL; patents, royalties, other intellectual property with Chugai Pharma, Bio-Rad, Sysmex and Guardant Health. Tara Maddala revealed employment with GRAIL and shares and other property interests with GRAIL. Other authors list numerous possible conflicts of interest. Graham reports that he serves in a conferencing office with Biopep Solution.

American Society of Clinical Oncology (ASCO) 2018. Submitted on June 4, 2018. Abstract LBA8501

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