Current Research Studies

SC-B615, Evaluation of ctDNA as a prognostic biomarker for patients with newly diagnosed localized Ewing sarcoma or osteosarcoma


What is the goal of the study?

Osteosarcoma and Ewing sarcoma are the most common primary bone malignancies affecting children and young adults. Approximately 70-75% of patients with localized Ewing sarcoma or osteosarcoma are expected to survive their disease with multi-agent chemotherapy regimens and local control of the primary tumor. Identification of patients with localized disease at high-risk of relapse after conventional therapy remains challenging. While a range of prognostic factors have been evaluated in these diseases, the presence of metastatic disease remains the strongest adverse prognostic factor at diagnosis. With the advent of next generation sequencing (NGS) approaches, we have an opportunity to evaluate circulating tumor DNA (ctDNA) for this purpose. Two custom NGS assays, TranSS-Seq and ULP-WGS, were used in the Crompton laboratory at the Dana-Farber Cancer Institute to demonstrate the feasibility of detecting ctDNA in the peripheral blood of patients with a range of sarcomas and pediatric cancers. As proof of concept, we evaluated these specific assays in two large retrospective cohorts of patients with localized osteosarcoma or Ewing sarcoma. We found 53% (41/77) of newly diagnosed patients with Ewing sarcoma and 57% (41/72) of newly diagnosed patients with osteosarcoma had detectable ctDNA. Among patients with newly diagnosed localized Ewing sarcoma, detectable ctDNA was associated with inferior 3-year event-free survival (EFS) in an initial (36% vs. 71%; p=0.012) and confirmatory cohort (54% vs. 100%; p=0.030). A similar pattern was observed in patients with newly diagnosed localized osteosarcoma (3-year EFS 66% if positive vs. 83% if negative; p=0.16). Increasing quantitative ctDNA was likewise associated with inferior outcomes in both diseases. Serial samples were not available from this retrospective study. In the current protocol, we aim to prospectively evaluate the prognostic impact of ctDNA as a peripheral blood biomarker using two custom NGS assays in patients with osteosarcoma or Ewing sarcoma. Participating patients with newly diagnosed localized disease will submit serial blood samples and clinical data. If validated, ctDNA holds potential for risk-stratification of patients with newly diagnosed osteosarcoma or Ewing sarcoma.

Who can participate in the study?

Please contact the study team listed below to learn more.

Study Team: