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Case series on clinical applications of liquid biopsy in pediatric solid tumors : towards improved diagnostics and disease monitoring

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Abstract
Background and aimsSolid tumors account for about 30% of all pediatric cancers. The diagnosis is typically based on histological and molecular analysis of a primary tumor biopsy. Liquid biopsies carry several advantages over conventional tissue biopsy. However, their use for genomic analysis and response monitoring of pediatric solid tumors is still in experimental stages and mostly performed retrospectively without direct impact on patient management. In this case series we discuss six clinical cases of children with a solid tumor for whom a liquid biopsy assay was performed and demonstrate the potential of liquid biopsy for future clinical decision making.MethodsWe performed quantitative real-time PCR (RT-qPCR), droplet digital PCR (ddPCR) or reduced representation bisulphite sequencing of cell-free DNA (cfRRBS) on liquid biopsies collected from six pediatric patients with a solid tumor treated between 2017 and 2023 at the Princess Maxima Center for Pediatric Oncology in the Netherlands. Results were used to aid in clinical decision making by contribution to establish a diagnosis, by prognostication and response to therapy monitoring.ResultsIn three patients cfRRBS helped to establish the diagnosis of a rhabdomyosarcoma, an Ewing sarcoma and a neuroblastoma (case 1-3). In two patients, liquid biopsies were used for prognostication, by MYCN ddPCR in a patient with neuroblastoma and by RT-qPCR testing rhabdomyosarcoma-specific mRNA in bone marrow of a patient with a rhabdomyosarcoma (case 4 and 5). In case 6, mRNA testing demonstrated disease progression and assisted clinical decision making.ConclusionThis case series illustrates the value of liquid biopsy. We further demonstrate and recommend the use of liquid biopsies to be used in conjunction with conventional methods for the determination of metastatic status, prognostication and monitoring of treatment response in patients with pediatric solid tumors.
Keywords
Cancer Research, Oncology, cfDNA (cell-free DNA), mRNA, solid tumor, RRBS, ddPCR, qPCR, pediatric cancer, liquid biopsy

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MLA
Gelineau, Nina U., et al. “Case Series on Clinical Applications of Liquid Biopsy in Pediatric Solid Tumors : Towards Improved Diagnostics and Disease Monitoring.” FRONTIERS IN ONCOLOGY, vol. 13, 2023, doi:10.3389/fonc.2023.1209150.
APA
Gelineau, N. U., van Barneveld, A., Samim, A., Van Zogchel, L., Lak, N., Tas, M. L., … Tytgat, G. (2023). Case series on clinical applications of liquid biopsy in pediatric solid tumors : towards improved diagnostics and disease monitoring. FRONTIERS IN ONCOLOGY, 13. https://doi.org/10.3389/fonc.2023.1209150
Chicago author-date
Gelineau, Nina U., Astrid van Barneveld, Atia Samim, Lieke Van Zogchel, Nathalie Lak, Michelle L. Tas, Yvette Matser, et al. 2023. “Case Series on Clinical Applications of Liquid Biopsy in Pediatric Solid Tumors : Towards Improved Diagnostics and Disease Monitoring.” FRONTIERS IN ONCOLOGY 13. https://doi.org/10.3389/fonc.2023.1209150.
Chicago author-date (all authors)
Gelineau, Nina U., Astrid van Barneveld, Atia Samim, Lieke Van Zogchel, Nathalie Lak, Michelle L. Tas, Yvette Matser, Annelies M. C. Mavinkurve-Groothuis, Martine van Grotel, Jószef Zsiros, Natasha K. A. van Eijkelenburg, Rutger R. G. Knops, Roelof van Ewijk, Karin P. S. Langenberg, Ronald De Krijger, Laura S. Hiemcke-Jiwa, Ruben Van Paemel, Lotte Cornelli, Katleen De Preter, Bram De Wilde, Ellen Van Der Schoot, and Godelieve Tytgat. 2023. “Case Series on Clinical Applications of Liquid Biopsy in Pediatric Solid Tumors : Towards Improved Diagnostics and Disease Monitoring.” FRONTIERS IN ONCOLOGY 13. doi:10.3389/fonc.2023.1209150.
Vancouver
1.
Gelineau NU, van Barneveld A, Samim A, Van Zogchel L, Lak N, Tas ML, et al. Case series on clinical applications of liquid biopsy in pediatric solid tumors : towards improved diagnostics and disease monitoring. FRONTIERS IN ONCOLOGY. 2023;13.
IEEE
[1]
N. U. Gelineau et al., “Case series on clinical applications of liquid biopsy in pediatric solid tumors : towards improved diagnostics and disease monitoring,” FRONTIERS IN ONCOLOGY, vol. 13, 2023.
@article{01HTHN58PXV9BE1JRDFKEA8RZE,
  abstract     = {{
Background and aimsSolid tumors account for about 30% of all pediatric cancers. The diagnosis is typically based on histological and molecular analysis of a primary tumor biopsy. Liquid biopsies carry several advantages over conventional tissue biopsy. However, their use for genomic analysis and response monitoring of pediatric solid tumors is still in experimental stages and mostly performed retrospectively without direct impact on patient management. In this case series we discuss six clinical cases of children with a solid tumor for whom a liquid biopsy assay was performed and demonstrate the potential of liquid biopsy for future clinical decision making.MethodsWe performed quantitative real-time PCR (RT-qPCR), droplet digital PCR (ddPCR) or reduced representation bisulphite sequencing of cell-free DNA (cfRRBS) on liquid biopsies collected from six pediatric patients with a solid tumor treated between 2017 and 2023 at the Princess Maxima Center for Pediatric Oncology in the Netherlands. Results were used to aid in clinical decision making by contribution to establish a diagnosis, by prognostication and response to therapy monitoring.ResultsIn three patients cfRRBS helped to establish the diagnosis of a rhabdomyosarcoma, an Ewing sarcoma and a neuroblastoma (case 1-3). In two patients, liquid biopsies were used for prognostication, by MYCN ddPCR in a patient with neuroblastoma and by RT-qPCR testing rhabdomyosarcoma-specific mRNA in bone marrow of a patient with a rhabdomyosarcoma (case 4 and 5). In case 6, mRNA testing demonstrated disease progression and assisted clinical decision making.ConclusionThis case series illustrates the value of liquid biopsy. We further demonstrate and recommend the use of liquid biopsies to be used in conjunction with conventional methods for the determination of metastatic status, prognostication and monitoring of treatment response in patients with pediatric solid tumors.}},
  articleno    = {{1209150}},
  author       = {{Gelineau, Nina U. and van Barneveld, Astrid and Samim, Atia and Van Zogchel, Lieke and Lak, Nathalie and Tas, Michelle L. and Matser, Yvette and Mavinkurve-Groothuis, Annelies M. C. and van Grotel, Martine and Zsiros, Jószef and van Eijkelenburg, Natasha K. A. and Knops, Rutger R. G. and van Ewijk, Roelof and Langenberg, Karin P. S. and Krijger, Ronald De and Hiemcke-Jiwa, Laura S. and Van Paemel, Ruben and Cornelli, Lotte and De Preter, Katleen and De Wilde, Bram and Van Der Schoot, Ellen and Tytgat, Godelieve}},
  issn         = {{2234-943X}},
  journal      = {{FRONTIERS IN ONCOLOGY}},
  keywords     = {{Cancer Research,Oncology,cfDNA (cell-free DNA),mRNA,solid tumor,RRBS,ddPCR,qPCR,pediatric cancer,liquid biopsy}},
  language     = {{eng}},
  pages        = {{16}},
  title        = {{Case series on clinical applications of liquid biopsy in pediatric solid tumors : towards improved diagnostics and disease monitoring}},
  url          = {{http://doi.org/10.3389/fonc.2023.1209150}},
  volume       = {{13}},
  year         = {{2023}},
}

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