Multi-cancer early detection screening from a blood test
Multi-cancer early detection (MCED) testing is a new approach to screening for cancer. While recommended single-cancer screenings play an important role in detecting five specific cancers today – breast, cervical, colorectal, lung (smokers considered at risk) and prostate cancers – nearly 70% of deaths are caused by cancers without recommended screening.*1 Adding a blood-based multi-cancer early detection test can help screen for many of the deadliest cancers that don’t have recommended screening today.
Benefits of multi-cancer early detection screening
Treating cancer starts with knowing you have it. Most cancers show no symptoms until later stages, when treatment options may be limited. The public health goal of commercializing an MCED test is to increase cancer detection rates without increasing the burden on healthcare systems. To do this, GRAIL developed a test with high (>99%) specificity that is able to predict the origin of the cancer while minimizing testing-associated potential risks, including overdiagnosis.
*Assumes screening is available for all prostate, breast, cervical, and colorectal cancer cases and 43% of lung cancer cases (based on the estimated proportion of lung cancers that occur in screen-eligible individuals older than 40 years).
How the Galleri multi-cancer early detection test works
Cancers growing in the body shed DNA into the bloodstream, and although there are many types of cancer, the DNA fragments act like a unique “fingerprint” of cancer.
The Galleri test detects DNA fragments circulating in the blood and uses a machine learning algorithm to determine whether those DNA fragments originate from healthy cells or cancer cells, and for the ~1% of patients that screen positive, predict the most likely origin of the cancer. Galleri can identify DNA shed by cancer cells while the patient is still asymptomatic, when it may be more easily treated and potentially curable.
The Galleri test does not detect a signal for all cancers and not all cancers can be detected in the blood. False positive and false negative results do occur. The Galleri test identifies DNA in the bloodstream shed by cancer cells and does not predict future genetic risk for cancer. Galleri should be used in addition to healthcare provider recommended screening tests.
Two principles of biology behind the Galleri test: DNA shedding & methylation
DNA shedding is the natural process by which cells in the body shed small amounts of DNA into the bloodstream. Cancerous cells, if present in the body, also release DNA and so the blood may carry a mixture of DNA fragments from healthy and diseased or cancerous cells. To determine if each DNA fragment in the blood came from a cancerous cell or a healthy cell, we analyze methylation patterns.
Methylation is a natural process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence by controlling which sections of DNA turn on or off. Typically, methylation turns genes “off” and demethylation turns genes “on.” GRAIL uses advanced machine learning algorithms and pattern recognition to “read” methylation patterns.
Using these two principles, the Galleri test has three scientific steps:
- Extract and sequence the DNA fragments from the blood to “read” the methylation patterns (assay)
- Determine if DNA fragments may have originated from cancerous cells (machine learning classifier)
- If cancerous DNA fragments are identified, use pattern recognition to predict the organ associated with the DNA fragments (cancer signal origin prediction, or CSO).
The Galleri test should be used in addition to recommended cancer screenings
The Galleri test is intended to be used in addition to guideline recommended single-cancer screening tests. Single-cancer screenings recommended for certain patients include breast, cervical, colorectal, lung and prostate cancers.2
The Galleri test can screen for many of the deadliest cancers that do not currently have recommended screening.
Doing more to screen for cancer
Published, modeled data shows that adding annual testing with a multi-cancer early detection blood test to usual care screening tests may shift detection to earlier stages, suggesting that the five-year cancer-related mortality rate could be reduced by 26% with a 50% reduction in late-stage cancer incidence.3
The Galleri test is recommended for use in adults with an elevated risk for cancer, such as those aged 50 or older. The Galleri test does not detect all cancers and should be used in addition to routine cancer screening tests recommended by a healthcare provider. Galleri is intended to detect cancer signals and predict where in the body the cancer signal is located. Use of Galleri is not recommended in individuals who are pregnant, 21 years old or younger, or undergoing active cancer treatment.
Results should be interpreted by a healthcare provider in the context of medical history, clinical signs and symptoms. A test result of “Cancer Signal Not Detected” does not rule out cancer. A test result of “Cancer Signal Detected” requires confirmatory diagnostic evaluation by medically established procedures (e.g. imaging) to confirm cancer.
If cancer is not confirmed with further testing, it could mean that cancer is not present or testing was insufficient to detect cancer, including due to the cancer being located in a different part of the body. False-positive (a cancer signal detected when cancer is not present) and false-negative (a cancer signal not detected when cancer is present) test results do occur. Rx only.
GRAIL’s clinical laboratory is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) and accredited by the College of American Pathologists (CAP). The Galleri test was developed, and its performance characteristics were determined by GRAIL. The Galleri test has not been cleared or approved by the U.S. Food and Drug Administration. GRAIL’s clinical laboratory is regulated under CLIA to perform high-complexity testing. The Galleri test is intended for clinical purposes.
References
1. American Cancer Society Cancer Facts and Figures 2022. Available at: https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2022.html. [GRAIL, LLC. Data on file: GA-2021-0065]
2. US Preventive Services Task Force. A,B,C grade recommendations, cancer, screenings [cited 2023 Oct 23]. https://www.uspreventiveservicestaskforce.org/uspstf/topic_search_results
3. Hubbell E, Clarke CA, Aravanis AM, et al. Modeled reductions in late-stage cancer with a multi-cancer early detection test. Cancer Epidemiol Biomarkers Prev. 2021;30(3):460-8. doi: 10.1158/1055-9965.EPI-20-1134