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

David S. Shulman, Kelly Klega, Alma Imamovic-Tuco, Andrea Clapp, Anwesha Nag, Aaron R. Thorner, Eliezer Van Allen, Gavin Ha, Stephen L. Lessnick, Richard Gorlick, Katherine A. Janeway, Patrick J. Leavey, Leo Mascarenhas, Wendy B. London, Kieuhoa T. Vo, Kimberly Stegmaier, David Hall, Mark D. Krailo, Donald A. Barkauskas, Steven G. DuBoisBrian D. Crompton

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)615-621
Number of pages7
JournalBritish journal of cancer
Volume119
Issue number5
DOIs
StatePublished - Aug 28 2018

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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