Highlights
- •Robot-assisted brainstem biopsy for pontine diffuse midline gliomas (DMG) is feasible and safe.
- •Real-time drug testing on patient-derived DMG cells define individualised treatments.
- •Targeted agents as paxalisib can be successfully integrated into the care of DMG.
Abstract
Background
Children diagnosed with diffuse midline gliomas (DMG) have an extremely poor overall
survival: 9–12 months from diagnosis with currently no curative treatment options.
Given DMG molecular heterogeneity, surgical biopsies are needed for molecular profiling
and as part of enrolment into molecular-based and precision medicine type clinical
interventions. In this study, we describe the results of real time profiling and drug
testing at the diffuse intrinsic pontine glioma/DMG Research Centre at University
Children's Hospital Zurich.
Method
Biopsies were taken using a frame based stereotactic robot system (NeuroMate®, Renishaw)
at University Children's Hospital Zurich. Tissue samples were evaluated to confirm
diagnosis by H3K27M and H3K27 trimethylation loss. Genomic analyses were done using
a variety of platforms (INFORM, Oncomine, UCSF500 gene panel).
Cell lines were developed by mechanical tissue dissociation and verified by either
sequencing or immunofluorescence staining confirming H3K27M mutation and used afterwards
for drug testing.
Results
Twenty-five robot-assisted primary biopsies were successfully performed. Median hospital
stay was 2 days (range 1–4 days). Nine low-passage patient-derived cells were developed,
whereas 8 cell lines were used to inform response to clinically relevant drugs. Genome
and RNA expression were used to further guide treatment strategies with targeted agents
such as dual PI3K/mTOR inhibitor paxalisib.
Conclusion
We established a systematic workflow for safe, robot-assisted brainstem biopsies and
in-house tissue processing, followed by real-time drug testing. This provides valuable
insights into tumour prognostic and individual treatment strategies targeting relevant
vulnerabilities in these tumours in a clinically meaningful time frame.
Keywords
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Article info
Publication history
Published online: November 28, 2022
Accepted:
October 17,
2022
Received in revised form:
September 28,
2022
Received:
July 30,
2022
Identification
Copyright
© 2022 Published by Elsevier Ltd.
