Artikel
Brainstem biopsy in paediatric diffuse intrinsic pontine glioma in the era of precision medicine – the INFORM study experience
Hirnstamm-Biopsie bei pädiatrischem diffusem Ponsgliom im Rahmen der Präzisionsmedizin – die INFORM-Erfahrung
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Veröffentlicht: | 8. Mai 2019 |
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Gliederung
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Objective: Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive pediatric brain tumor with fatal outcome. The INFORM registry offers comprehensive molecular profiling of high-risk tumors in order to identify target alterations for potential precision therapy. We analyzed molecular characteristics and clinical information after brainstem biopsy of all enrolled newly diagnosed DIPGs for risk-benefit assessment.
Methods: From 02/2015–02/2018, 21 subsequent primary DIPG cases were enrolled in the nation-wide multi-center INFORM registry study following brainstem biopsy. Whole-genome, whole-exome sequencing and DNA methylation analysis were performed, and RNA-sequencing was added in case of sufficient material. Standardized questionnaires and the INFORM electronic case report form retrieved clinical data.
Results: Tumor material obtained from brainstem biopsy was sufficient for DNA analysis in all cases and RNA analysis in 16/21 cases. In 16/21 cases (76%) potential targetable alterations were identified including an EZH2 alteration not previously described in DIPG. In 5/21 cases molecular information was used for initiation of targeted treatment. The majority of patients (19/21) presented with neurological deficits at diagnosis. Newly arising or worsening of neurological deficits post-biopsy occurred in nine patients. Symptoms were reversible or improved notably in eight cases.
Conclusion: In this multi-center study setting, brainstem biopsy of DIPG was feasible and yielded sufficient material for comprehensive molecular profiling. Relevant molecular targets were identified impacting clinical management in a substantial subset. Death or severe bleeding occurred in none of the cases. 1/20 patients experienced unilateral paresthesia possibly related to biopsy.