Chordomas, though rare, represent one of the most difficult cancers to treat and track. These tumors, thought to arise from remnants of the notochord, affect only a few hundred people in the United States each year. Surgery is the only treatment modality shown to significantly alter survival in large studies, but it comes fraught with its own challenges. Because many of these cancers recur locally—and are typically removed with en bloc resection with extensive spinal stabilization and plastic surgery reconstruction—subsequent surgeries are often more and more difficult, if not impossible.

 

To get around these problems, researchers are investigating new adjunct and targeted therapies, including various radiation methods, novel chemotherapies and immunotherapies. However, being able to determine whether these therapies are having their intended effect can be tricky—on MRI and CT scans, tumors might not change in size over time, or might look more or less dense, fibrotic, or necrotic.

 

“It’s unclear whether these changes represent true changes in disease or are just an evolution of the tumor over time,” says Johns Hopkins neurosurgeon Chetan Bettegowda.

 

To help track whether adjunct treatments are having their intended effect, doctors need tools beyond MRI and CT. That’s why Bettegowda and his colleagues are developing what they call “liquid

biopsies”—blood tests that shed some information about tumor status.

 

Chordomas are good candidates for this type of blood test, Bettegowda explains, because unlike many central nervous system tumors, early data suggest that they shed DNA into the bloodstream. By looking for particular biomarkers in this DNA that are unique to these cancers and tracking changes over time, researchers can more effectively assess chordoma growth and changes in response to adjuvant therapies.

 

Bettegowda and his colleagues are currently performing genetic testing on numerous samples gathered from chordoma patients at Johns Hopkins, searching for the minute differences that separate chordoma DNA from that of healthy cells. Concurrently,

they’re taking blood samples from patients before, during and after treatment to gauge how levels of chordoma DNA might rise or fall over the course of a therapy, a surrogate for how the tumor itself might be growing or shrinking. This type of test might also be used in the weeks and months immediately after surgery to look for minimally residual disease, Bettegowda says, and leftover cells that could lead to recurrence, and might suggest a need for more aggressive adjunct therapies.

 

The researchers are also pursuing a test for the rs2305089 single nucleotide polymorphism (SNP) located in the brachyury gene, a developmental gene known to play a role in notochord development. Bettegowda and his colleagues have shown that while the vast majority of individuals that develop chordomas have this particular SNP variation, those that develop chordomas without this SNP tend to have worse outcomes.

 

Developing a blood test for this SNP or chordoma DNA in general could lead to better clinical decision making for these challenging tumors, Bettegowda says. “Our ultimate goal,” says Bettegowda, “is to be more selective in the therapies we deliver to treat these patients in the most effective way possible.”