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.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Shulman DS,Klega K,Imamovic-Tuco A,Clapp A,Nag A,Thorner AR,Van Allen E,Ha G,Lessnick SL,Gorlick R,Janeway KA,Leavey PJ,Mascarenhas L,London WB,Vo KT,Stegmaier K,Hall D,Krailo MD,Barkauskas DA,DuBois SG,Crompton Bdoi
10.1038/s41416-018-0212-9subject
Has Abstractpub_date
2018-08-01 00:00:00pages
615-621issue
5eissn
0007-0920issn
1532-1827pii
10.1038/s41416-018-0212-9journal_volume
119pub_type
杂志文章abstract:BACKGROUND:Activated anaplastic lymphoma kinase (ALK) gene fusions are recurrent events in a small fraction of colorectal cancers (CRCs), although these events have not yet been exploited as in other malignancies. METHODS:We detected ALK protein expression by immunohistochemistry and gene rearrangements by fluorescenc...
journal_title:British journal of cancer
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journal_title:British journal of cancer
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