New progress toward personalized treatment for chordoma

Take-home message for patients

Researchers have identified two molecular subtypes of chordoma associated with different prognoses. They also found that the subtypes can be detected through blood samples, suggesting that someday chordoma diagnosis and prognosis could be determined without biopsy or surgery. More work is underway to confirm and build on these findings before they can be used to guide treatment in the clinic. If you or someone you love has been diagnosed with chordoma and have questions about what recent research findings like these might mean for you, our Patient Navigators can help.

Chordoma patients who receive standard treatments such as radiation and surgery experience a wide range of outcomes; some encounter recurrence and metastasis relatively quickly, while others live decades free from this disease. Scientists are working to better understand the biological factors that contribute to these varied outcomes in order to replace a one-size-fits-all treatment approach with more personalized strategies.

Significant progress toward this goal has just emerged from a research team at the University of Toronto. With support from the Chordoma Foundation and the Canadian Cancer Society, Gelareh Zadeh, MD, PhD with graduate student Jeffrey Zuccato, MDand colleagues used state-of-the-art techniques to systematically survey the epigenetic landscape of a large cohort of chordoma tumor samples. (Epigenetics refers to various modifications to DNA that affect which genes are turned on and off. Certain epigenetic changes can cause cancer to develop or influence the behavior of cancer cells.)

The analysis uncovered two distinct epigenetic signatures in chordomas, corresponding to different underlying biology and different patient prognosis: an “immune-infiltrated” subtype, marked by an abundance of immune cells like neutrophils and B lymphocytes, and a “cellular” subtype, characterized by relatively high tumor cellularity (the amount of tumor cells within a tumor). Median survival was 6 years in the immune-infiltrated subtype compared to about 17 years in the cellular subtype.

In some cases, the investigators had access to blood samples matched to each tumor. Using machine-learning algorithms, they were able to distinguish between the two subtypes in the plasma of these blood samples. This represents a possible step toward noninvasive chordoma diagnosis and ability to determine prognosis.

Eventually, the findings could help point to therapeutic strategies for patients whose tumors have a signature suggestive of more aggressive disease, and may lead to personalized treatment approaches. For example, if a patient could be confirmed to have a more aggressive chordoma subtype, their surgeon could pursue a greater extent of tumor resection; conversely, a patient with better prognosis could avoid “overtreatment” and unnecessary side effects.

The findings were published in Neuro-Oncology. We’re grateful for our partnership with the Canadian Cancer Society, which made this work possible, and for the dedicated fundraising efforts and generosity of the Canadian members of our Board of Directors, Steven Golick and Ed Les.

Next steps

Before these new findings can be translated to patient care, they’ll need to be confirmed in a greater number of patient samples and other laboratories; two other Foundation-supported teams are already poised to do so. Additionally, recent publications by other groups offer complementary progress toward noninvasive detection of chordoma and identifying biomarkers that could guide treatment strategies. Together, these projects represent a coordinated approach to informing better, more personalized care for chordoma patients.

Meanwhile, Dr. Zadeh recently forged a partnership with another University of Toronto researcher, Thomas Kislinger, PhD, one of the world’s leading experts in cancer proteomics (the study of proteins present in cells and how they function). By working together to overlay epigenomic and proteomic data, they expect to discover additional, more granular chordoma subtypes. They also aim to discover proteins on the surface of chordoma cells that could serve as targets for emerging treatments — like systemic therapies that selectively target tumor cells, and various types of immunotherapy. Ultimately, their goal is to enable these new treatment modalities — which are proving to be highly effective against many other cancers — to help chordoma patients, too.