Researchers develop a highly sensitive method of finding residual cancer after treatment

By Christopher Vaughan

Institute researchers have developed a new method of detecting cancer DNA in the bloodstream that can find nearly all residual disease after treatment.

“Older methods would miss 25-50% of the cases in which some cancer cells remained after treatment,” said Maximilian Diehn, MD, PhD. “This new method seems to be able to catch virtually everybody with residual disease.” Diehn and Ash Alizadeh, MD, PhD, call their method PhasED-Seq and tested it on most common lymphoma subtype, and also did proof-of-concept studies on solid tumors. Diehn and Alizadeh, both members of the Stanford Institute for Stem Cell Biology and Regenerative Medicine, were senior authors on the research, which was published in the journal Nature Biotechnology. David Kurtz, MD, PhD and Joanne Soo, MD were joint first authors on the paper.

The researchers still need to confirm that the method works more broadly across diverse solid tumors and other blood cancers besides lymphoma. They also caution that the method needs further prospectively validation in clinical trials before it can be widely used for clinical decision-making. 

Every year, cancer specialists have more therapies to choose from when treating cancer. Often these treatments work well, but the fear of every doctor and patient is that a therapy does not eliminate the cancer completely, even though there are no detectable signs of the cancer after treatment. When even a relative few cancer-initiating cells are left behind, the cancer can come roaring back, often stronger than before. 

“The amount of tumor present in the body after treatment strongly predicts risk of later disease progression and death across cancer types and across different treatment types, so it’s important that we can detect residual cancer as soon as possible after treatment,” Alizadeh said. “We now know from several cancers that intervention based on the presence of minimal residual disease can improve outcomes, and this PhasED-Seq method now offers an ultrasensitive approach to find such residual disease.”

When cancer cells die, they shed DNA into the bloodstream, and the circulating DNA that comes from cancer can be detected because some bits of DNA have particular cancer mutations. Alizadeh and Diehn assemble a panel of the mutations associated with a particular tumor type with a cancer found in individual patients. They have been refining methods of detecting these cancer-derived DNA segments with extreme sensitivity and accuracy.

“The old methods could detect cancer DNA at a level of about one part in 50,000 or so,” Diehn said. With this new method we can detect on part in one or two million or so, so it’s at least a 40- to 50-fold improvement.”