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

Front Oncol. 2023 Aug 17:13:1209150. doi: 10.3389/fonc.2023.1209150. eCollection 2023.

Authors

Nina U Gelineau^{1

2}, Astrid van Barneveld¹, Atia Samim¹, Lieke Van Zogchel^{1

2}, Nathalie Lak^{1

2}, Michelle L Tas¹, Yvette Matser¹, Annelies M C Mavinkurve-Groothuis¹, Martine van Grotel¹, Jószef Zsiros¹, Natasha K A van Eijkelenburg¹, Rutger R G Knops¹, Roelof van Ewijk¹, Karin P S Langenberg¹, Ronald De Krijger^{1

3}, Laura S Hiemcke-Jiwa^{1

3}, Ruben Van Paemel^{4

5

6}, Lotte Cornelli^{4

7}, Katleen De Preter^{4

6

7}, Bram De Wilde^{4

5

6}, Ellen Van Der Schoot², Godelieve Tytgat^{1

2}

Affiliations

¹ Princess Máxima Center for Pediatric Oncology Research, Utrecht, Netherlands.
² Department of Experimental Immunohematology, Sanquin Research, Amsterdam, Netherlands.
³ Department of Pathology, University Medical Center Utrecht, Utrecht, Netherlands.
⁴ Department of Biomolecular Medicine, Ghent University, Ghent, Belgium.
⁵ Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, Ghent University, Ghent, Belgium.
⁶ Research Institute, Ghent University, Ghent, East Flanders, Belgium.
⁷ VIB-UGent Center for Medical Biotechnology, Gent, Belgium.

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.

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

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.