For some blood cancers, such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), determining whether patients need aggressive treatment usually revolves around a set of laboratory tests to make adjustments. genetic identification.
Some of these tests rely on technology created more than 60 years ago and used clinically for the last three decades.
Now, a new study from the University of Washington School of Medicine in St. Louis shows that whole genome sequences are at least as accurate and often superior to conventional genetic tests that help determine the treatment for a patient’s blood cancer. Genome sequencing technology is continuously declining in cost and has recently reached a level similar to that of conventional experiments. In addition, results can be returned to patients in just a few days, making a whole genome sequence a potentially viable approach for determining the optimal treatment regimen for a particular patient. .
The study is published in the March 11 issue of The New England Journal of Medicine.
Selecting the appropriate treatment for cancer patients often depends on identifying a range of different genetic changes in the patient’s tumor cells. Our study suggests that whole genome sequences are a reliable and practical method for detecting all mutations that are important for assessing the risk of recurrence for AML and MDS patients, using a single test . This procedure can be performed when conventional testing methods are not successful and may be applied to other cancers, including solid tumors. This means that patients with other types of cancer could benefit from rapid clinical genome sequencing. “
David H. Spencer, MD, PhD, Senior Research Author and Associate Professor of Medicine and Medical Director of Clinical Classification Facility, McDonnell Genome Institute
The study focused on patients with AML, bone marrow-induced blood cancer, and MDS, a group of disorders in which the bone marrow does not produce enough normal blood cells. Both are often fatal, but many patients can be treated more effectively if given the right treatment.
Patients with leukemia or MDS are divided into three risk categories based on the results of genetic tests. Patients at favorable risk are usually treated with chemotherapy alone. Patients at unfavorable risk often require more intensive treatment at the time of diagnosis -; usually chemotherapy and cell gas transplantation (previously known as bone marrow transplantation). For moderate-risk patients, the optimal treatment is less obvious, and their treatments may vary, depending on each patient’s state of health, personal preferences, and physician guidance.
For nearly three decades, patients have been assigned to these risk categories based on the way their chromosomes look under a microscope. Recently, physicians have begun to incorporate genetic sequences of a limited number of genes into the analysis, but such classification usually does not identify all changes that are important for treatment decisions to be made. instructions. Whole genome sequencing can identify changes in chromosomes and genes, but is rarely carried out outside of research studies because of its cost and the time it takes to classify and analyze an entire genome.
“For these types of blood cancers, routine chromosome analysis is an essential part of routine screening,” Spencer said. “We know from research studies that whole genome sequences can detect the types of chromosomal disorders, so that part of our study will not be a terrible surprise. What we have shown is that genome sequence has reached it now. practical, fast, economical, clinically feasible and accessible for routine patient testing. “
According to the researchers, the technical costs for a sequence in this study were approximately $ 1,900 per patient. This amount is similar to the cost of a laboratory for routine genetic testing for an AML patient, which is typically between $ 1,000 and $ 2,000. Actual costs for clinical use of whole genome classification are likely to be higher due to additional costs associated with implementing such a test in a clinical laboratory setting.
In the new study, the researchers -; including co-authors Eric J. Duncavage, MD, professor of pathology & immunology; Molly C. Schroeder, PhD, assistant professor of pathology & immunology; and Timothy J. Ley, MD, Professor of Medicine Lewis T. and Rosalind B. Apple -; they evaluated blood samples from 263 patients with these blood cancers by following the whole genomes of the patients, and compared these results with traditional genetic tests from the same patients. Patients were treated at the Siteman Cancer Center at Barnes-Jewish Hospital and the University of Washington School of Medicine.
The researchers found that whole genome sequences identified all of the major genomic disorders by the standard method -; called karyotyping -; and, importantly, identified additional genetic anomalies in 17% of cases. Of the 263 patients, 117 were new patients; samples from the other patients were subsequently examined.
For the newly re-diagnosed patients, whole genome sequences found additional genetic information in approximately 25% of cases. This new information changed the risk category for 19 patients. In general, changing the risk category can change patients ’treatment options. The researchers also showed that this series could do relatively quickly, returning results in an average of five days but in as little as three.
One of the disadvantages of karyotyping is that some patients have uncertain results. Karyotyping requires a sample that contains live cells, and sometimes there are not enough live cells in the sample to determine the patient’s risk segment.
Complete genome sequences, by contrast, do not want living cells. It uses only a small sample of DNA from a patient’s cancer cells. In this study, the researchers found that whole genome sequencing may pose a risk to patients who obtained inconclusive results from the traditional karyotype-based analyzes. According to the researchers, inconclusive results or assay failure can occur in up to 20% of AML patients.
“Uncertain results are extremely difficult, as we want to be able to offer patients the most appropriate treatment at the start of treatment. While value in genetic testing is limited, it can miss important results that are often relevant. We have worked for years to streamline a whole set of genomes so that they can be used routinely, “said Ley, who led the team at the McDonnell Genome Institute that followed the first cancer genome (from an AML patient) directly. 12 years ago.
“The whole series of cancer genomes, first developed here at the University of Washington, transformed our understanding of cancer and how it can be treated,” said Schroeder. working on it because it shows that whole genome sequences have become an effective, practical and clinically useful tool for testing patients when they are diagnosed with AML or MDS. “
According to Spencer, the majority of patients who changed their risk category based on the genome approach moved to less favorable risk categories. This suggests that whole genome sequences may be able to identify patients in the unfavorable risk region, allowing them to receive the most appropriate treatment in advance.
The researchers will continue to evaluate whole genome sequences for AML and MDS patients as part of clinical trials. In addition, patients with AML and MDS treated at the Siteman Cancer Center will be offered a complete genome sequencing. For those eligible, funding for a complete genome sequencing assay, called ChromoSeq, will be provided by BJC HealthCare.
“One of the most interesting aspects of this study is that the results are immediately translated into patient care,” Duncavage said. “In collaboration with the McDonnell Genome Institute and the Department of Pathology & Immunology, we are pleased to launch a clinical version of this assay that will be available to patients. We are proud to be able to offer a complete genome sequence for AML and MDS Patients, and we hope to extend this to other cancers very soon. “
Peter Campbell, MD, PhD, leads cancer genome sequencing studies at the Wellcome Sanger Institute in Cambridge, UK the real time, “said Campbell, who was not involved in this work.” This interesting study shows, first, that this technology can be applied in clinical practice in the world, and secondly. instead, that we can make more accurate treatment options for patients with blood cancer. Our job now is to adopt this plan for blood cancers. and apply it for all cancers. “
Source:
Washington University in St. Louis