@article{fe4e48e0578c497c92f64018bcd97ff0,
title = "Detection of circulating tumour DNA is associated with inferior outcomes in Ewing sarcoma and osteosarcoma: a report from the Children{\textquoteright}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.",
author = "Shulman, {David S.} and Kelly Klega and Alma Imamovic-Tuco and Andrea Clapp and Anwesha Nag and Thorner, {Aaron R.} and {Van Allen}, Eliezer and Gavin Ha and Lessnick, {Stephen L.} and Richard Gorlick and Janeway, {Katherine A.} and Leavey, {Patrick J.} and Leo Mascarenhas and London, {Wendy B.} and Vo, {Kieuhoa T.} and Kimberly Stegmaier and David Hall and Krailo, {Mark D.} and Barkauskas, {Donald A.} and DuBois, {Steven G.} and Crompton, {Brian D.}",
note = "Funding Information: Funding: This work was supported in part by the National Institutes of Health (NIH) Grant K23 CA154530 (S.G.D.); NIH Grant P30AI027763 to the UCSF-GIVI Center for AIDS Research (UCSF Flow Cytometry Core Laboratory); NIH Grant R01 CA204915 (K.S.); NIH Grand T32 CA136432-08 (D.S.S.); Curing Kids Cancer (K.S.); Alex{\textquoteright}s Lemonade Funding Information: Stand Foundation (K.T.V., S.G.D., D.S.S.); Frank A. Campini Foundation (K.T.V., S.G.D.); NIH Grant K08 CA188073-01A1 (B.D.C.); Children{\textquoteright}s Oncology Group (COG) Translational Pilot Studies Program for Solid Malignancies (B.D.C.); Boston Children{\textquoteright}s Hospital Translational Research Program (B.D.C.); Pediatric Cancer Research Foundation (B.D.C.); Go 4 The Goal Foundation (B.D.C.); QuadW Foundation (D.H., M.D.K., D.A. B.); and the following support to COG: St. Baldrick{\textquoteright}s Foundation, U10CA180884, U10CA180886, U10CA180899, U10CA098543, U10CA098413, and U24CA114766 (COG). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or other funding agencies. Publisher Copyright: {\textcopyright} 2018, Cancer Research UK.",
year = "2018",
month = aug,
day = "28",
doi = "10.1038/s41416-018-0212-9",
language = "English (US)",
volume = "119",
pages = "615--621",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "5",
}