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Ounce of Lung Cancer Prevention, Worth a Pound of Cure


An expert from Texas Oncology offers perspective on findings from the CCGA study – presented at the 2018 ASCO Annual Meeting – which may support the use of a blood test to detect lung cancer earlier.

Researchers are one step closer to having a blood test that can detect early-stage lung cancer, according to results from the Circulating Cell-free Genome Atlas (CCGA) study.

Findings from the large, ongoing study, which were presented at the 2018 American Society of Clinical Oncology Annual Meeting, provided preliminary evidence that blood tests analyzing free-floating or cell-free DNA using a genome-wide sequencing approach detected 41 percent of early stage (stage 1 to 3A) lung cancers.

When detected and diagnosed early, survival rates significantly increase. Therefore, the US Preventive Services Task Force (USPSTF) recommends for people with a significant smoking history to be screened with low-dose CT; however, such screening is extremely underutilized — partially because critics of the screening say it leads to the risk of false positives and overdiagnosis.

Debra Patt, M.D., MPH, medical oncologist with Texas Oncology, a member of the US Oncology Network, offered her own perspective of the study, noting how important these results could be for early screening.

“We always want a better mouse trap. In the words of Benjamin Franklin, ‘An ounce of prevention is worth a pound of cure.’ And so, if we can detect cancer early, we can potentially cure it more easily and help more patients survive with less medical intervention,” she said in an interview with CURE.

Analysis of plasma cell-free DNA, also called liquid biopsies, is already widely used for selecting targeted therapies in advanced lung cancer. However, the CCGA study is now the first to show that cell-free DNA analysis may be feasible for early detection of lung cancer.

Geoffrey R. Oxnard, M.D., associate professor of medicine at Dana-Farber Cancer Institute and Harvard Medical School, and colleagues conducted the CCGA study as part of the larger ongoing GRAIL trial, which has enrolled more than 12,000 of the planned 15,000 participants — including 70 percent with cancer and 30 percent without cancer – across 141 sites in the United States and Canada.

At the annual meeting, Oxnard reported from the first preplanned sub-study, which included 20 different cancer types across all stages, from the CCGA study evaluating three prototype sequencing assays performed on blood samples from approximately 1,700 participants. In this presentation, the researchers focused on three different assays to detect cancer in 127 people with stage 1-4 lung cancer, which included:

  • targeted sequencing to detect somatic, or non-inherited mutations,
  • whole-genome sequencing (WGS) to detect somatic gene copy number changes, and
  • whole-genome bisulfite sequencing (WGBS) of cell-free fDNA to detect abnormal cell-free fDNA methylation patterns, or epigenetic changes.

Oxnard and colleagues compared these patients with 580 controls with similar ages, of which 85 percent and 43 percent were ever-smokers, and 46 percent and 22 percent were men, respectively.

The biologic signal for lung cancer appeared to be comparable across all three assays, and the signal increased with disease stage. At 98 percent specificity, the WGBS assay detected 41 percent of stage 1 to 3A cancers and 89 percent of stage 3B-4 cancers; while the WGS and targeted assays were similarly effective, detecting 38 percent and 51 percent of early stage cancers and 87 percent and 89 percent of late-stage cancers, respectively.

Initial results of the CCGA study showed that all three prototype assays could detect lung cancer with a low rate of false positive findings, meaning a test that suggests a person has cancer when, in actuality, there is no cancer.

Of the 580 controls in the study, five individuals showed a cancer-like signal across all three assays, of which two were subsequently diagnosed with cancer (one with stage 3 ovarian cancer and one with stage 2 endometrial cancer).

In addition, more than 54 percent of somatic, or non-inherited, mutations were detected white blood cells in the blood samples versus the tumors, which is how these mutations are typically discovered. Oxnard noted that these mutations are likely due to the natural aging processes and will be important to consider when developing blood tests for early detection of cancer.

“Two years ago, it was a pipe dream,” Oxnard said during a press cast. “It’s a huge [advance] and it means this is going to be a reality going forward.”

Patt added that these are certainly exciting times as researchers lay the groundwork for early lung cancer detection. “I am very excited because I think there is a future for cell free DNA to detect occult cancer, and for that to be part of a better mouse trap for us to detect cancer early,” she added. “I think that we are going to see a lot more from the GRAIL study, and a lot more out of cell free DNA because it offers a lot of promise. Is it ready for prime-time screening? Probably not just yet.”

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