Dataset Information

Detection of circulating tumour DNA is associated with inferior outcomes in Ewing sarcoma and osteosarcoma: a report from the Children's Oncology Group.

ABSTRACT:

Background

New prognostic markers are needed to identify patients with Ewing sarcoma (EWS) and osteosarcoma unlikely to benefit from standard therapy. We describe the incidence and association with outcome of circulating tumour DNA (ctDNA) using next-generation sequencing (NGS) assays.

Methods

A NGS hybrid capture assay and an ultra-low-pass whole-genome sequencing assay were used to detect ctDNA in banked plasma from patients with EWS and osteosarcoma, respectively. Patients were coded as positive or negative for ctDNA and tested for association with clinical features and outcome.

Results

The analytic cohort included 94 patients with EWS (82% from initial diagnosis) and 72 patients with primary localised osteosarcoma (100% from initial diagnosis). ctDNA was detectable in 53% and 57% of newly diagnosed patients with EWS and osteosarcoma, respectively. Among patients with newly diagnosed localised EWS, detectable ctDNA was associated with inferior 3-year event-free survival (48.6% vs. 82.1%; p = 0.006) and overall survival (79.8% vs. 92.6%; p = 0.01). In both EWS and osteosarcoma, risk of event and death increased with ctDNA levels.

Conclusions

NGS assays agnostic of primary tumour sequencing results detect ctDNA in half of the plasma samples from patients with newly diagnosed EWS and osteosarcoma. Detectable ctDNA is associated with inferior outcomes.

SUBMITTER: Shulman DS

PROVIDER: S-EPMC6162271 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Publications

Detection of circulating tumour DNA is associated with inferior outcomes in Ewing sarcoma and osteosarcoma: a report from the Children's Oncology Group.

Shulman David S DS Klega Kelly K Imamovic-Tuco Alma A Clapp Andrea A Nag Anwesha A Thorner Aaron R AR Van Allen Eliezer E Ha Gavin G Lessnick Stephen L SL Gorlick Richard R Janeway Katherine A KA Leavey Patrick J PJ Mascarenhas Leo L London Wendy B WB Vo Kieuhoa T KT Stegmaier Kimberly K Hall David D Krailo Mark D MD Barkauskas Donald A DA DuBois Steven G SG Crompton Brian D BD

British journal of cancer 20180821 5

<h4>Background</h4>New prognostic markers are needed to identify patients with Ewing sarcoma (EWS) and osteosarcoma unlikely to benefit from standard therapy. We describe the incidence and association with outcome of circulating tumour DNA (ctDNA) using next-generation sequencing (NGS) assays.<h4>Methods</h4>A NGS hybrid capture assay and an ultra-low-pass whole-genome sequencing assay were used to detect ctDNA in banked plasma from patients with EWS and osteosarcoma, respectively. Patients were ...[more]

PMID: 30131550

Similar Datasets

Project description:PurposeIdentification of discrete sub-groups associated with treatment response and resistance in localized Ewing sarcoma (EWS) remains a challenge. The primary objective of the Children's Oncology Group biology study AEWS18B1-Q was to perform molecular characterization of a large cohort of patients with localized Ewing sarcoma treated on prospective trials with modern standard of care therapy.MethodsWe analyzed clinical and molecular features from patients with localized EWS enrolled on AEWS0031, AEWS1031, or INT-0154 frontline trials. All patients had available FFPE tissue, frozen tissue, or whole-genome amplified material. Sequencing was performed for identification of canonical fusions, recurrent copy number alterations (CNAs), and alterations in TP53 and STAG2. Where available, tissue was analyzed for loss of STAG2 protein expression. Molecular features were evaluated for their association with cumulative incidence of relapse in univariate and multivariable analyses.ResultsThree hundred and fifty-one cases had sufficient tissue, which in most cases was extracted from two FFPE slides. EWS canonical fusions were identified in 282 cases (80.3%). Pathogenic mutations in TP53 and STAG2 were identified in 5.1% and 7.6% of cases, respectively and 63.1% of cases were found to have recurrent CNAs. In univariate analysis, there was an increased cumulative incidence of relapse in patients with TP53 mutation (5-year cumulative incidence of relapse 43%, CI [17%, 67%] vs. 22%, CI [17%, 27%]; Gray's test P = 0.039), STAG2 mutation (53%, CI [29%, 73%] vs. 21%, CI [16%, 26%]; P < 0.001), and recurrent CNAs (30%, CI [22%, 37%] vs. 16%, CI [9%, 24%]; P = 0.005). In a multivariable analysis, STAG2 mutation was the only molecular biomarker that remained prognostic.ConclusionThis is a prospective validation of the molecular prognostic features of localized EWS receiving standard of care therapy on therapeutic clinical trials. Building on prior work, patients with STAG2 mutations were at high risk of relapse.

Dataset Information

Detection of circulating tumour DNA is associated with inferior outcomes in Ewing sarcoma and osteosarcoma: a report from the Children's Oncology Group.

Background

Methods

Results

Conclusions

Publications

Detection of circulating tumour DNA is associated with inferior outcomes in Ewing sarcoma and osteosarcoma: a report from the Children's Oncology Group.

Similar Datasets

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