Bottom Line: Doctors have had limited success developing targeted therapies for the treatment of glioblastoma and lower-grade glioma, the most common primary brain cancers in adults. Targeted therapy requires matching drugs to the genetic profile of a tumor, which can substantially change throughout the course of the disease. Keeping track of these changes is particularly challenging in people with brain tumors because collecting tumor DNA requires brain surgery. But experts from Memorial Sloan Kettering have shown that utilizing the minimally invasive procedure commonly called a spinal tap may help doctors better understand a tumor’s changing genetic makeup, offering clues into such traits as tumor aggressiveness.
Findings and Method: Brain tumors can shed small amounts of DNA into the fluid surrounding the brain and spinal cord, so researchers collected fluid from 85 people in whom glioma had returned following initial treatment. (The patients consented to have their fluid analyzed for research purposes.) The team found circulating tumor DNA (ctDNA) in 42 of the 85 samples. When they reviewed patients’ medical and pathology backgrounds, they discovered that people with these bits of tumor genetic material in their cerebrospinal fluid were more likely to have aggressive disease.
Using MSK IMPACT™, the research team sequenced the ctDNA and found a broad range of genetic alterations, most of which were also present in patients’ matching tumor samples. However, in people for whom there was a longer interval between tumor biopsy and cerebrospinal fluid collection, researchers observed patterns of genetic evolution, with some alterations appearing only in the tumor tissue or the spinal fluid.
Author Comment: “This study showed that we can use a spinal fluid sample to observe molecular changes in a tumor in a considerable fraction of patients with recurrent glioma,” said MSK neurologist Alexandra Miller, the study’s lead author. “We know that tumors evolve over the course of the disease, and this could be a way to help track and understand the mutational changes.
“Our next step,” she continues, “will be to understand how specific therapies influence this genetic change and to determine whether this type of testing could be useful to understand the causes of drug resistance in glioma. It might also be helpful to diagnose patients whose tumors cannot be biopsied due to the location of the tumor.”
Journal: “Tracking tumor evolution in glioma through liquid biopsies of cerebrospinal fluid” was published in Nature on January 23, 2019.
Funding: This research was supported by the National Brain Tumor Society Defeat GBM Initiative, the National Institutes of Health (1 R35 NS105109 01 and P30CA008748), Cycle of Survival, the American Brain Tumor Association, the Marie-Josée and Henry R. Kravis Center for Molecular Oncology at MSK, the Brain Tumor Center at MSK, and MSK’s Neuro-Oncology Research in Translation Program.