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

doi:10.1038/s41416-018-0212-9

Cited by 100 publications

(119 citation statements)

References 36 publications

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“…72,82,91,92 NGS assays have also been utilized to detect variants associated with a worse outcome, including TP53 mutations and STAG2 loss in Ewing sarcoma, 8q gain in osteosarcoma, MYCN amplification in neuroblastoma, 1q gain in Wilms tumor, and PAX3 gene rearrangements in alveolar rhabdomyosarcoma. 82,83 Although prior studies identified known prognostic genetic features in ctDNA, we demonstrated that detection of ctDNA itself provided prognostic information at diagnosis in patients with Ewing sarcoma and osteosarcoma. 83 Using a hybrid-capture NGS assay, ctDNA could be detected in over half of patients with Ewing sarcoma from a cooperative group biobank of plasma samples.…”

Section: First Authormentioning

confidence: 71%

“…Adalsteinsson et al showed that ctDNA can be quantified by measuring genome‐wide segmental copy‐number changes from ultralow‐passage WGS (ULP‐WGS) using the ichorCNA algorithm . We recently applied this approach to the most common non‐CNS pediatric solid tumors, and we demonstrated that the majority of pediatric malignant tumors shed ctDNA at detectable levels . One advantage of this approach is that quantification of ctDNA does not require prior tumor profiling or the need for a germline sample.…”

Section: Detection Quantification and Characterization Of Ctdna In mentioning

confidence: 98%

“…Therefore, NGS strategies must be selected to balance three main profiling considerations: (1) the proportion of the genome targeted for sequencing; (2) the depth of sequencing desired; and (3) the cost of sequencing each sample (Figure ). For example, low‐passage WGS can identify ctDNA by detecting chromosomal copy‐number events . This approach efficiently identifies copy‐number events in samples with a high fraction of tumor DNA (≥3%) at a relatively low cost but is unable to identify specific base‐pair substitutions, focal copy‐number events, or translocations.…”

Section: Detection Quantification and Characterization Of Ctdna In mentioning

confidence: 99%

“…Proof‐of‐concept studies found a correlation between plasma dPCR and tumor genomic analysis for detection of MYCN amplification, ALK amplification, and ALK hotspot mutations in neuroblastoma . NGS assays have also been utilized to detect variants associated with a worse outcome, including TP53 mutations and STAG2 loss in Ewing sarcoma, 8q gain in osteosarcoma, MYCN amplification in neuroblastoma, 1q gain in Wilms tumor, and PAX3 gene rearrangements in alveolar rhabdomyosarcoma …”

Section: Clinical Exploration Of Ctdna In Pediatric Solid Tumorsmentioning

confidence: 99%

“…60 We recently applied this approach to the most common non-CNS pediatric solid tumors, and we demonstrated that the majority of pediatric malignant tumors shed ctDNA at detectable levels. 82,83 One advantage of this approach is that quantification of ctDNA does not require prior tumor profiling or the need for a germline sample. Therefore, ctDNA analyses can be performed in settings where access to such samples may be limited or incomplete, as is often the case in multi-institutional prospective clinical trials of rare cancers.…”

Section: Ngsmentioning

confidence: 99%

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Assessment of circulating tumor DNA in pediatric solid tumors: The promise of liquid biopsies

Abbou

Shulman

DuBois

et al. 2019

Pediatric Blood & Cancer

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Circulating tumor DNA (ctDNA) can be detected in the blood and body fluids of patients using ultra-sensitive technologies which have the potential to improve cancer diagnosis, risk stratification, non-invasive tumor profiling, and tracking of treatment response and disease recurrence. As we begin to apply “liquid biopsy” strategies in children with cancer, it is important to tailor our efforts to the unique genomic features of these tumors and address the technical and logistical challenges of integrating biomarker testing. This article reviews the literature demonstrating the feasibility of applying liquid biopsy to pediatric solid malignancies and suggests new directions for future studies.

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Section: First Authormentioning

confidence: 71%

Section: Detection Quantification and Characterization Of Ctdna In mentioning

confidence: 98%

Section: Detection Quantification and Characterization Of Ctdna In mentioning

confidence: 99%

Section: Clinical Exploration Of Ctdna In Pediatric Solid Tumorsmentioning

confidence: 99%

Section: Ngsmentioning

confidence: 99%

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Assessment of circulating tumor DNA in pediatric solid tumors: The promise of liquid biopsies

Abbou

Shulman

DuBois

et al. 2019

Pediatric Blood & Cancer

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Clinical significance of circulating tumor cells and cell‐free DNA in pediatric rhabdomyosarcoma

et al. 2022

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Liquid biopsy analysis represents a powerful and noninvasive tool to uncover biomarkers for disseminated disease assessment and longitudinal monitoring of patients. Herein, we explored the value of circulating and disseminated tumor cells (CTC and DTC, respectively) and cell‐free DNA (cfDNA) in pediatric rhabdomyosarcoma (RMS). Peripheral blood and bone marrow samples were analyzed to detect and enumerate CTC and DTC, respectively. We used the epithelial cellular adhesion molecule (EpCAM)‐based CellSearch platform coupled with an automatic device to collect both EpCAM‐positive and EpCAM‐low/negative CTCs. The standard assay was implemented, including the mesenchymal marker desmin. For selected cases, we molecularly profiled primary tumors and liquid biopsy biomarkers using whole‐exome sequencing and droplet digital PCR, respectively. RMS patients with metastatic disease had a significantly higher number of CTCs compared to those with localized disease, whereas DTCs were detected independently of disease presentation. The use of the desmin marker remarkably increased the identification of CTCs and DTCs in RMS samples. Of note, CTC clusters were detected in RMS patients with disseminated disease. Further, cfDNA and CTC molecular features closely reflected the molecular makeup of primary tumors and informed of disease course.

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Clinical utility of circulating tumor DNA sequencing with a large panel in patients with advanced soft‐tissue sarcomas

Blanchi

Taleb

Bayle

et al. 2023

Cancer Communications

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To the editor Soft-tissue sarcomas (STS) represent a very heterogeneous group of rare tumors including more than 100 different subtypes [1]. Surgery and neo/adjuvant radiation therapy represent the cornerstone of treatment for STS. However, despite an optimal resection of the tumor, up to 40% of patients will develop metastatic relapse and will die from the disease [1]. Doxorubicin represents the first-line standard of care for patients with advanced disease since the 1970s, despite several attempts to identify better regimens. The median overall survival (OS) of patients with metastatic disease is < 18 months and has only modestly improved over the past 20 years [2].We and others have previously reported that nextgeneration sequencing (NGS) of tumor tissues allows the identification of genomic aberrations with the potential to influence and personalize therapy in up to 50% of patients with advanced STS [3,4].Genomic profiling of circulating tumor DNA (ctDNA) is increasingly used to tailor therapy in cancer patients. Indeed, such liquid biopsy has several advantages: noninvasiveness, reduced turnaround times for faster results, and the ability to fully capture the landscape of tumor heterogeneity [5].The aims of the present study were to investigate the impact of ctDNA profiling in a large cohort of patients with advanced STS included in two prospective precision medicine studies and to decipher the ctDNA molecular landscape of sarcoma.

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

Abstract: 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.

Cited by 100 publications

References 36 publications

Assessment of circulating tumor DNA in pediatric solid tumors: The promise of liquid biopsies

Assessment of circulating tumor DNA in pediatric solid tumors: The promise of liquid biopsies

Clinical significance of circulating tumor cells and cell‐free DNA in pediatric rhabdomyosarcoma

Clinical utility of circulating tumor DNA sequencing with a large panel in patients with advanced soft‐tissue sarcomas

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