Liquid biopsies, used to identify and monitor the progress of cancer, can also detect a blood cell disorder that puts patients at higher risk of developing blood cancers. The findings will be presented at the 34th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapies in Barcelona.
The key to liquid biopsies lies in detecting the DNA that tumors shed into the bloodstream, which is called cell-free DNA (cfDNA). Liquid biopsy detects cfDNA in blood samples taken from patients, allowing doctors to better characterize a cancer, select the best therapy, or monitor disease progression and response to treatment, all without the need for additional biopsies. more invasive.
A condition called clonal hematopoiesis, an incidental and relatively common finding on liquid biopsies, led researchers at the Institut Gustave Roussy (Villejuif, France) to wonder if biopsies could also be used routinely to identify patients who have or might be at increased risk of developing future blood cancers, such as myelodysplastic syndrome (a blood cell disorder that starts in the bone marrow) or acute myeloid leukemia.
Clonal hematopoiesis occurs when one type of cell, the hematopoietic stem cell, which can develop into different types of blood cells and is produced in the bone marrow, begins to produce cells with the same genetic mutation —which is different from the genetic pattern of normal blood cells—. These cells can also shed DNA into the blood.
Early detection could prevent complications during cancer treatments
Marco Tagliamento
Hospital Gustave Roussy
Previous studies had shown that the absolute risk of HC progressing to blood cancer is about 1% per yearwith a 10-fold increase in relative risk.
Between March and October 2021, researchers took liquid biopsies from 1,416 patients with a variety of solid tumors who had been enrolled in the Gustave Roussy Cancer Profiling (STING) study.
“We found that 113 patients, 8%, had at least one clonal hematopoiesis mutation that could be considered to put them at increased risk of developing blood cancers throughout their lives. Of these patients, 45 were referred to our hematology unit by their oncologist and five were later diagnosed with blood cancer: one with myelomonocytic leukemia, two with myelodysplastic syndrome and two with essential thrombocythemia”, says Marco Tagliamento, from the Institut Gustave Roussy.
The researchers believe that when liquid biopsies reveal a high-risk HC feature in patients, further hematologic evaluation is needed in some circumstances to reveal the true risk of developing a blood cancer or also to discover cases in which that a patient already suffers from one without knowing it.
“Early detection could prevent complications during cancer treatments; for example, changes in blood counts and subsequent discontinuation or delay of treatment. It could also point to potential diagnostic and therapeutic avenues for clinicians to consider for hematologic diseases.», Signed by Tagliamento.
During work to identify patients who should be referred for further investigation, the Gustave Roussy Molecular Tumor Board carefully considered each case to identify the genetic mutations involved in CH.
Only a few specific HC mutations are likely to predict an increased risk of blood cancer later in life
Ruth Plummer
University of Newcastle
Case-by-case evaluation is crucial, says Tagliamento. “Different aspects should be considered when evaluating the potential impact and management of high-risk clonal hematopoiesis in patients who already have cancer. These relate, for example, to patients, their medical history, and underlying cancers. They should all be part of a balanced assessment made for each individual case.”
We will continue to apply this approach within the Gustave Roussy Molecular Tumor Board. We want to implement and improve the efficiency of the algorithm to select patients with solid cancers who could benefit from a haematological evaluation”, he added. The results are part of a team project led by Mihaela Aldea and Jean Baptiste Micol.
For Ruth Plummer, from the University of Newcastle (United Kingdom) and president of the 34th EORTC-NCI-AACR Symposium, who was not involved in the research, she acknowledges that the study reveals an additional function of the information obtained from liquid biopsies.
But he underscores the importance of assessing the context for each individual patient. “Cancer patients have a lot to worry about, so it’s up to their doctors to take into account the patient’s clinical condition and treatment plan.”
Plummer points out that due to the potential anxiety of patients it will not always be appropriate to highlight a possible increased risk of developing an additional blood cancer in later years. “It is likely that only a few specific clonal hematopoiesis mutations predict an increased risk of developing blood cancer at some point in the future. This study suggests that patients with these mutations should be referred for further evaluation and even then, decisions about what would be best for these patients will depend on a variety of other factors.”