Abstract
Conventional chondrosarcoma is the most common primary bone tumor in adults. Prognosis corresponds with tumor grade but remains variable, especially for individuals with grade (G) II disease. There are currently no biomarkers available for monitoring or prognostication of chondrosarcoma. Circulating tumor DNA (ctDNA) has recently emerged as a promising biomarker for a broad range of tumor types. To date, little has been done to study the presence of ctDNA and its potential utility in the management of sarcomas, including chondrosarcoma. In this study, we have assessed ctDNA levels in a cohort of 71 patients, 32 with sarcoma, including 29 individuals with central chondrosarcoma (CS) and 39 with locally aggressive and benign bone and soft tissue tumors, using digital PCR. In patients with CS, ctDNA was detected in pretreatment samples in 14/29 patients, which showed clear correlation with tumor grade as demonstrated by the detection of ctDNA in all patients with GIII and dedifferentiated disease (n = 6) and in 8/17 patients with GII disease, but never associated with GI CS. Notably detection of ctDNA preoperatively in GII disease was associated with a poor outcome. A total of 14 patients with CS had ctDNA levels assessed at multiple time points and in most patients there was a clear reduction following surgical removal. This research lays the foundation for larger studies to assess the utility of ctDNA for chondrosarcoma diagnosis, prognostication, early detection of residual disease and monitoring disease progression.
Highlights
Conventional central chondrosarcoma (CS) is the most common bone sarcoma in adults with an incidence of ~1/100,000/year
Of the 29 patients with Isocitrate dehydrogenase type 1 (IDH1)-mutant CS selected for this study, 15 patients had only preoperative samples analyzed whereas a variable number of pre-and post-operative serial blood samples was available throughout the course of treatment from the remaining 14 patients
Correlation of the Circulating tumor DNA (ctDNA) data with clinical records revealed that detection of preoperative ctDNA in 8/17 patients with GII CS was associated with a poor prognosis compared to those in whom ctDNA was not detected: 3/8 ctDNA-p ositive patients with GII disease had died by the end of the study (CS06, CS15, CS21) (P-v alue = 0.0448 Log-rank (Mantel-C ox test) (Fig. 2A)
Summary
Conventional central chondrosarcoma (CS) is the most common bone sarcoma in adults with an incidence of ~1/100,000/year. Clinical outcome has not changed in 30 years and tumor grade (G) is the best prognosticator of metastatic disease, and survival, aside from when the lesions occur in the phalanges as these have a negligible risk of metastasis. Resistant to chemotherapy and radiotherapy, GII and III disease are treated by en bloc excision and a prosthetic implant when required. Patients with dedifferentiated CS may be treated with chemotherapy [4]
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