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

Nina U. Gelineau; 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; Godelieve Tytgat

doi:10.3389/fonc.2023.1209150

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

Nina U. Gelineau^*, 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 WildeEllen Van Der Schoot, Godelieve Tytgat^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background and aims: Solid 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. Methods: We 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 Máxima 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. Results: In 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. Conclusion: This 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.

Original language	English
Article number	1209150
Journal	Frontiers in oncology
Volume	13
DOIs	https://doi.org/10.3389/fonc.2023.1209150
Publication status	Published - 2023

Keywords

cfDNA (cell-free DNA)
ddPCR
liquid biopsy
mRNA
pediatric cancer
qPCR
RRBS
solid tumor

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Gelineau, N. U., van Barneveld, A., Samim, A., Van Zogchel, L., Lak, N., Tas, M. L., Matser, Y., Mavinkurve-Groothuis, A. M. C., van Grotel, M., Zsiros, J., van Eijkelenburg, N. K. A., Knops, R. R. G., van Ewijk, R., Langenberg, K. P. S., Krijger, R. D., Hiemcke-Jiwa, L. S., Van Paemel, R., Cornelli, L., De Preter, K., ... 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, Article 1209150. https://doi.org/10.3389/fonc.2023.1209150

@article{d270b8d2f9e9455da907f6779c2ec0a9,

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

abstract = "Background and aims: Solid 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. Methods: We 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 M{\'a}xima 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. Results: In 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. Conclusion: This 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 = "cfDNA (cell-free DNA), ddPCR, liquid biopsy, mRNA, pediatric cancer, qPCR, RRBS, solid tumor",

author = "Gelineau, {Nina U.} and {van Barneveld}, Astrid and Atia Samim and {Van Zogchel}, Lieke and Nathalie Lak and Tas, {Michelle L.} and Yvette Matser and Mavinkurve-Groothuis, {Annelies M.C.} and {van Grotel}, Martine and J{\'o}szef Zsiros 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 Lotte Cornelli and {De Preter}, Katleen and {De Wilde}, Bram and {Van Der Schoot}, Ellen and Godelieve Tytgat",

note = "Publisher Copyright: Copyright {\textcopyright} 2023 Gelineau, van Barneveld, Samim, Van Zogchel, Lak, Tas, Matser, Mavinkurve-Groothuis, van Grotel, Zsiros, van Eijkelenburg, Knops, van Ewijk, Langenberg, Krijger, Hiemcke-Jiwa, Van Paemel, Cornelli, De Preter, De Wilde, Van Der Schoot and Tytgat.",

year = "2023",

doi = "10.3389/fonc.2023.1209150",

language = "English",

volume = "13",

journal = "Frontiers in oncology",

issn = "2234-943X",

publisher = "Frontiers Media S. A.",

}

Gelineau, NU, van Barneveld, A, Samim, A, Van Zogchel, L, Lak, N, Tas, ML, Matser, Y, Mavinkurve-Groothuis, AMC, van Grotel, M, Zsiros, J, van Eijkelenburg, NKA, Knops, RRG, van Ewijk, R, Langenberg, KPS, Krijger, RD, Hiemcke-Jiwa, LS, Van Paemel, R, Cornelli, L, De Preter, K, De Wilde, B, Van Der Schoot, E & Tytgat, G 2023, 'Case series on clinical applications of liquid biopsy in pediatric solid tumors: towards improved diagnostics and disease monitoring', Frontiers in oncology, vol. 13, 1209150. https://doi.org/10.3389/fonc.2023.1209150

TY - JOUR

T1 - Case series on clinical applications of liquid biopsy in pediatric solid tumors

T2 - towards improved diagnostics and disease monitoring

AU - Gelineau, Nina U.

AU - van Barneveld, Astrid

AU - Samim, Atia

AU - Van Zogchel, Lieke

AU - Lak, Nathalie

AU - Tas, Michelle L.

AU - Matser, Yvette

AU - Mavinkurve-Groothuis, Annelies M.C.

AU - van Grotel, Martine

AU - Zsiros, Jószef

AU - van Eijkelenburg, Natasha K.A.

AU - Knops, Rutger R.G.

AU - van Ewijk, Roelof

AU - Langenberg, Karin P.S.

AU - Krijger, Ronald De

AU - Hiemcke-Jiwa, Laura S.

AU - Van Paemel, Ruben

AU - Cornelli, Lotte

AU - De Preter, Katleen

AU - De Wilde, Bram

AU - Van Der Schoot, Ellen

AU - Tytgat, Godelieve

N1 - Publisher Copyright: Copyright © 2023 Gelineau, van Barneveld, Samim, Van Zogchel, Lak, Tas, Matser, Mavinkurve-Groothuis, van Grotel, Zsiros, van Eijkelenburg, Knops, van Ewijk, Langenberg, Krijger, Hiemcke-Jiwa, Van Paemel, Cornelli, De Preter, De Wilde, Van Der Schoot and Tytgat.

PY - 2023

Y1 - 2023

N2 - Background and aims: Solid 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. Methods: We 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 Máxima 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. Results: In 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. Conclusion: This 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.

AB - Background and aims: Solid 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. Methods: We 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 Máxima 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. Results: In 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. Conclusion: This 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.

KW - cfDNA (cell-free DNA)

KW - ddPCR

KW - liquid biopsy

KW - mRNA

KW - pediatric cancer

KW - qPCR

KW - RRBS

KW - solid tumor

UR - http://www.scopus.com/inward/record.url?scp=85169689126&partnerID=8YFLogxK

U2 - 10.3389/fonc.2023.1209150

DO - 10.3389/fonc.2023.1209150

M3 - Article

AN - SCOPUS:85169689126

SN - 2234-943X

VL - 13

JO - Frontiers in oncology

JF - Frontiers in oncology

M1 - 1209150

ER -

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

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