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CTOS 2019: Navigating the sarcoma maze with CGP

Every cancer presents its challenges, but sarcomas are particularly troublesome. They are tricky to diagnose and have few treatment options.

Sarcomas are a group of rare and diverse cancers. With more than 80 subtypes, this type of cancer can be susceptible to misdiagnosis and there are very limited treatment guidelines beyond standard chemotherapy.1 This is where comprehensive genomic profiling (CGP) can help remove the guess work by identifying alterations in the genes driving the cancer that might be prognostic or inform targeted therapies.

CGP additionally provides valuable information to sarcoma researchers. At the Connective Tissue Oncology Society (CTOS) annual conference, which just wrapped up in Tokyo, the utility of CGP in sarcomas was evident.

Sarcoma research presented at CTOS emphasized CGP’s utility in providing genomic information to help inform more accurate diagnoses and matching sarcoma patients to treatments or clinical trial options based on genomic insights. Other studies highlighted the value of CGP in identifying new findings that can inform novel targets and further drug development.

Improving care today


One study presented at CTOS in collaboration with Memorial Sloan Kettering revealed a troubling statistic brought to light by the CGP results: 11% of sarcoma patients in the study had been previously misdiagnosed.2 Based on incorrect diagnostic results, it is possible these patients could have experienced a delay in receiving appropriate treatment, or worse, could have been prescribed an ineffective treatment.

More than a third of these patients were identified as possessing actionable alterations, meaning the findings from the CGP test indicated they could be matched with a corresponding FDA-approved therapy or clinical trial option.

Because the specific genomics of this diverse form of cancer are so varied, the use of CGP at initial diagnosis can help appropriately identify specific subtypes of sarcomas and point patients and their doctors to therapy options that are available now.

Advancing research


Another study presented at the meeting shares new insights on the emerging evidence demonstrating unique molecular characteristics and potential treatment approaches for cancers with the EWSR1-NFATc2 fusion, an extremely rare gene fusion in sarcoma.3

In this study, researchers assessed 14,500 profiles from Foundation Medicine’s FoundationCore® genomic insights database and pinpointed 11 patients with this rare gene fusion. Previously considered a subtype of Ewing’s sarcoma and treated as such, the EWSR1-NFATc2 fusion was shown to result in a unique sarcoma subtype - molecularly distinct from Ewing’s sarcoma. Furthermore, this fusion resulted in increased activity of the PI3 kinase pathway, which indicates that the cancer may be therapeutically targetable. Further studies are required to confirm this finding.

Additionally, the researchers reported one patient with EWSR1-NFATc2 fusion was treated with an mTOR inhibitor and had “extraordinary long-term disease stabilization,” setting the stage for investigation of a targeted treatment for these patients.

The ability to identify such a small subset (0.076%), made possible by our more than 350,000 genomic profiles within the FoundationCore® database, is an important way that Foundation Medicine is advancing cancer research through insights on new and novel targets. The better we can characterize a person’s cancer, the better we’re able to study it, and, hopefully, treat it.


In another study, our team used FoundationOne®Heme–our CGP test combining DNA and RNA–to study the gene fusion driving desmoplastic small round cell tumors (DSRCT), which CTOS designated as the highlighted sarcoma at this year’s meeting.4 Although DSRCT is rare, the FoundationCore® database includes more than 100 sequenced samples of this sarcoma sub-type.

We identified a gene fusion indicated to be a driver of DSRCT and predicted that a subset of patients–12% of 109 DSRCT samples evaluated by CGP–would have an immune recognition of this gene fusion. This suggests a potential benefit from immune checkpoint inhibition, which is exciting given that these patients lacked standard predictors of immunotherapy benefit, such as high tumor mutational burden (TMB) and high microsatellite instability (MSI).

We look forward to following further research into the potential of immune checkpoint inhibition in patients with this rare sarcoma.


Some sarcomas currently have no predictive biomarkers for treatment, so new approaches that guide treatment decisions are needed. In another study, researchers found that dysfunction of the succinate dehydrogenase (SDH) complex could be a target for novel treatments in paraganglioma (PGL), pheochromocytoma (Pheo) and gastrointestinal stromal tumor (GIST).5

Advancing patient care into the future

We are in the midst of an exciting time in sarcoma research. Recognizing that one third of sarcoma patients could have an actionable alteration underscores the importance of CGP testing at diagnosis, and these data continue to support the impact comprehensive genomic profiling can have in correcting or refining diagnosis and selecting matched therapies in sarcoma.2

Research continues to reveal powerful information about the hidden mechanics of sarcoma genomics, and momentum is building toward better sarcoma care. Foundation Medicine is at the forefront of these advances and my hope is that we can continue to make important advances for this rare cancer.


1 Casali, et al. Soft tissue and visceral sarcomas: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment, and follow-up. Annals of Oncology. 2018;29(Supp 4):iv51-iv67. doi:10.1093/annonc/mdy096.

2 Percentage of misdiagnosis limited to study - Grounder, et al. “Comprehensive genomic profiling (CGP) of desmoplastic small round cell tumors (DSRCT) identifies predicted neoantigenic gene fusions.” Abstract presented at CTOS 2019.

3 Seligson, et al. “Comprehensive genomic analysis of EWSR1-NFATc2 fusion sarcomas identify distinctive.” Abstract presented at CTOS 2019.

4 Jin, et al. “Comprehensive genomic profiling (CGP) of desmoplastic small round cell tumors (DSRCT) identifies predicted neoantigenic gene fusions.” Abstract presented at CTOS 2019.

5 Pavlick, et al. “Exploratory analysis of hybrid-capture based next generation sequencing confirms succinate dehydrogenase deficiency as the solitary genomic driver in paraganglioma, pheochromocytoma, and GIST.” Abstract presented at CTOS 2019.

November 21, 2019 Sherri Z. Millis, PhD Senior Manager, Clinical Training

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