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

被引：102

作者：

Shulman, David S. ^{[1
]}

Klega, Kelly ^{[1
]}

Imamovic-Tuco, Alma ^{[1
]}

Clapp, Andrea ^{[2
]}

Nag, Anwesha ^{[2
]}

Thorner, Aaron R. ^{[2
]}

Van Allen, Eliezer ^{[3
,4
]}

Ha, Gavin ^{[4
]}

Lessnick, Stephen L. ^{[5
,6
]}

Gorlick, Richard ^{[7
]}

Janeway, Katherine A. ^{[1
]}

Leavey, Patrick J. ^{[8
]}

Mascarenhas, Leo ^{[9
]}

London, Wendy B. ^{[1
]}

Vo, Kieuhoa T. ^{[10
]}

Stegmaier, Kimberly ^{[1
]}

Hall, David ^{[11
]}

Krailo, Mark D. ^{[11
,12
]}

Barkauskas, Donald A. ^{[11
,12
]}

DuBois, Steven G. ^{[1
]}

Crompton, Brian D. ^{[1
,4
,13
]}

机构：

[1] Harvard Med Sch, Dana Farber Boston Childrens Canc & Blood Disorde, Boston, MA 02115 USA

[2] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA

[3] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[4] Broad Inst, Cambridge, MA 02142 USA

[5] Ohio State Univ, Nationwide Childrens Hosp, Res Inst, Ctr Childhood Canc & Blood Dis, Columbus, OH 43210 USA

[6] Ohio State Univ, Div Pediat Heme Onc BMT, Columbus, OH 43210 USA

[7] MD Anderson Canc Ctr, Dept Pediat, Houston, TX USA

[8] Univ Texas Southwestern Med Ctr Dallas, Dept Pediat, Dallas, TX USA

[9] Univ Southern Calif, Keck Sch Med, Childrens Hosp Los Angeles, Div Hematol Oncol & Blood & Marrow Transplantat, Los Angeles, CA USA

[10] Univ Calif San Francisco, Sch Med, Dept Pediat, UCSF Benioff Childrens Hosp, San Francisco, CA USA

[11] Childrens Oncol Grp, Monrovia, CA USA

[12] Univ Southern Calif, Keck Sch Med, Dept Preventat Med, Los Angeles, CA USA

[13] Dept Pediat Oncol, 450 Brookline Ave, Boston, MA 02215 USA

来源：

BRITISH JOURNAL OF CANCER | 2018年 / 119卷 / 05期

基金：

美国国家卫生研究院;

关键词：

HIGH-GRADE OSTEOSARCOMA; PROGNOSTIC-FACTORS; GENOMIC LANDSCAPE; CHEMOTHERAPY; PLASMA; DISEASE; IDENTIFICATION; DIAGNOSIS; FRAMEWORK; BIOMARKER;

D O I：

10.1038/s41416-018-0212-9

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：615 / 621

页数：7

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