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A new method for determining the sequence of molecules in DNA can be used with a high degree of accuracy to detect small fragments of cancerous genetic material in blood samples taken from patients with cancer lung cancer, according to new research published in the leading cancer journal. Annals of Oncology [1] today (Wednesday).
The results of "liquid biopsy" badyzes in patients with non-small cell lung cancer (NSCLC) show that it is possible to identify genetic variants that are either at the origin of cancer, or its resistance to treatment. This offers physicians the opportunity to use liquid biopsies to help them choose the best treatment for patients based on the genetic makeup of their tumors.
US researchers have used a method of badyzing patient blood samples called "next-generation ultra-deep sequencing". It is to read the DNA fragments released by tumors into the blood – known as cell-free DNA (cfDNA) – 50,000 times on average, to guarantee the greatest accuracy in the detection of variants of any of the 37 genes commonly involved in the lung. Cancer.
The proportion of cfdNA from tumors is very small compared to non-cancer cells in the blood. It is therefore important to be able to detect the weak cDNA signals of the tumor and distinguish between them and the overwhelming background noise. To do this, the patient's white blood cells were also sequenced and used to filter non-cancerous signals from the bone marrow, a process called "clonal hematopoiesis filtering". Next-generation ultra-deep sequencing information [2] was introduced in a new computer algorithm that used machine learning to sift the "wheat" from "the weed" [3].
Researchers at the Memorial Sloan Kettering Cancer Center (MSK) in New York, the MD Anderson Cancer Center in Texas, and the Dana-Farber Cancer Institute in Boston collected blood samples from 127 patients with cancer. a newly diagnosed advanced NSCLC who subsequently metastasized. parts of the body or who had recurrent metastases. There were three groups of patients: 1) 91 in whom genetic mutations leading to cancer or making it resistant to treatment had been identified from a tumor tissue sample (a tissue biopsy); 2) 19 patients for whom the biopsy did not detect such mutations; and 3) 17 patients for whom there was no tissue biopsy or who was insufficient for the badysis.
In order to compare the performance of the fluid biopsy with the tissue biopsy in an unbiased manner, the liquid biopsy was tested "blindly", without it being known what tissue biopsy had already found. This allowed researchers to extrapolate the utility of liquid biopsy to detect mutations accurately in patients lacking sufficient tissue to test.
Dr. Bob T. Li, a medical oncologist from MSK, who led the research for the Actionable Genome Consortium, said, "We found out of the 91 patients in whom tissue biopsy revealed cancer-inducing mutations. , the badysis of the liquid biopsy detected 68, which gives a truly positive rate of 75%. Of the 19 patients without mutations detected in the tissue biopsy, the liquid biopsy also detected no mutation, which means that there were no false positives and gave a truly negative rate of 100%. "
He stated that the 75% rate of true positives was comparable to that of other digital methods of detecting lung cancer driver mutations.
Among the third group of 17 patients for whom no tissue biopsy was available, cfDNA badysis detected mutations inducing cancer in four patients. This was subsequently confirmed by a tissue biopsy in one patient, while the other three did not have subsequent tissue biopsy. Of the remaining 13 patients, subsequent tissue biopsies confirmed mutations in two of them, while the remaining 11 did not undergo subsequent biopsy.
"Our results suggest that fluid biopsy can play a complementary role to tissue biopsy in the treatment of lung cancer, because of its high specificity of 100%, which means that it is not Had false positives, a liquid biopsy could be performed first and serve as a guide to treatment, particularly when tissue biopsy may be inadequate or not feasible.The warning is that because of its modest rate of true positive 75 %, if the fluid biopsy is negative, a tissue biopsy is still needed, "he said.
Previous MSK research has shown that liquid biopsy can be taken and badyzed in about nine days, compared to 20 days for tissue biopsies – a time difference that can be important for very ill patients who can deteriorate rapidly.
Cancer-inducing or treatment-resistant mutations detected by tissue and fluid biopsies included changes in the EGFR, KRAS, ALK, ROS1, BRAF, HER2, RET, and MET genes for which existing targeted therapies exist. as new drugs or combinations of drugs under development.
Dr. Li concluded, "Liquid biopsy is a promising technology development that could help improve patient care, and we are continuing research on this innovative test, and these results are a step in the right direction for the field of medicine. liquid biopsy. "
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Remarks:
[1] "Next Generation Ultra-Deep Sequencing of DNA-Free Plasma Cells in Patients with Advanced Lung Cancer: Results of the Actionable Genome Consortium", by B.T. Li et al. Annals of Oncology. doi: 10.1093 / announce / mdz046 [2] Illumina Inc. has performed next-generation ultra-deep sequencing. [3] The machine learning algorithm was developed by a company called GRAIL in California, United States.Warning: AAAS and EurekAlert! are not responsible for the accuracy of the news releases published on EurekAlert! contributing institutions or for the use of any information via the EurekAlert system.
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