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Identifying relapse in lymphoma patients with circulating tumor DNA

3505577004_6fc17ba8c2_zCancer patients in remission often live on a knife's edge, wondering if their disease will recur. This possibility is more likely in some types of cancers than in others. One of these is diffuse large B-cell lymphoma, which is the most common blood cancer in this country. It's often successfully treated, but a significant minority of patients will relapse. Detecting these relapses early is critical, but difficult.

Hematologist and oncologists Ash Alizadeh, MD, PhD, and David Kurtz, MD, and former postdoctoral scholar Michael Green, PhD, wanted to find a better way to track disease progression in these patients. They've developed a new technique, published Friday in the journal Blood, that is more accurate and can detect relapses earlier than conventional methods.

"As a clinician, I care for many of these patients," Alizadeh explained to me. "Detecting relapse can be very difficult. It would be a major step forward to develop a way to identify these patients before they become sick again."

Detecting relapse can be very difficult. It would be a major step forward to develop a way to identify these patients before they become sick again.

The researchers turned to what's known as circulating tumor DNA in the blood. The approach, which was pioneered by Stanford bioengineer Stephen Quake, PhD, relies on the idea that when the cells in our body die, they rupture and release their contents, including their DNA, into our bloodstream. Tracking the rise and fall of the levels of these tiny snippets of genetic information can give insight into what is happening throughout the body.

When a B cell becomes cancerous, it begins to divide uncontrollably. Each of these cancer cells shares the DNA sequence of the original cell; as the cells multiply, so does the overall amount of that DNA sequence in the body. Alizadeh and his colleagues wondered whether tracking the levels of cancer-specific DNA in a patient’s blood could help them identify those patients in the early stages of relapse.

Currently patients in remission are monitored for relapse with regular physical exams and blood tests. Imaging techniques such as PET or CT scans can be used to look for residual disease, but they don’t detect every case, and often deliver false positive results. They are also costly and expose the patient to DNA-damaging radiation that could potentially cause secondary cancers years later.

As I describe in today's Inside Stanford Medicine:

The researchers studied 75 patients diagnosed with diffuse large B cell lymphoma. They identified the DNA sequence unique to each patient’s tumor and then used high-throughput sequencing to look for this sequence in the patient’s blood, both in the plasma (the straw-colored, cell-free liquid in which blood and immune cells circulate), and in the patient’s circulating immune cells.

The researchers found that, in patients known to be relapsing, they could reliably detect the tumor DNA in the plasma. In contrast, when they examined the circulating cells in the blood they could detect the disease in only 30 percent of the relapsing patients.

They then compared their plasma-based method with PET/CT scans. Studying patients who would go on to relapse, they found their new method identified all patients at the time of their relapse, and often was able to detect disease prior to relapse. Furthermore, the test was positive only in those patients who truly had relapsed disease. In contrast, a positive PET/CT scan was correct only 56% of the time.

Previously: Blood will tell: In Stanford study, tiny bits of circulating tumor DNA betray hidden cancers, Gene-sequencing rare tumors – and what it means for cancer research and treatment andSmoking gun or hit-and-run? How oncogenes make good cells go bad
Photo by Mike

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