Brainstem biopsy in pediatric diffuse intrinsic pontine glioma in the era of precision medicine: the INFORM study experience

Journal article

Publication Details

Author(s): Pfaff E, El Damaty A, Balasubramanian GP, Blattner-Johnson M, Worst BC, Stark S, Witt H, Pajtler KW, van Tilburg CM, Witt R, Milde T, Jakobs M, Fiesel P, Frühwald MC, Hernáiz Driever P, Thomale UW, Schuhmann MU, Metzler M, Bochennek K, Simon T, Dürken M, Karremann M, Knirsch S, Ebinger M, von Bueren AO, Pietsch T, Herold-Mende C, Reuss DE, Kiening K, Lichter P, Eggert A, Kramm CM, Pfister SM, Jones DT, Bächli H, Witt O
Journal: European journal of cancer
Publication year: 2019
Volume: 114
Pages range: 27-35
ISSN: 0959-8049


Purpose: Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive paediatric brain tumour with fatal outcome. The Individualised Therapy For Relapsed Malignancies In Childhood (INFORM) registry study offers comprehensive molecular profiling of high-risk tumours to identify target alterations for potential precision therapy. We analysed molecular characteristics and clinical data after brainstem biopsy of all enrolled newly diagnosed DIPGs. Patients and methods: From –February 2015 to February 2018, 21 subsequent primary DIPG cases were enrolled in the nation-wide multicentre INFORM registry study after brainstem biopsy. Whole-genome, whole-exome sequencing and DNA methylation analysis were performed, and RNA-sequencing was added in case of sufficient material. Clinical data were obtained from standardised questionnaires and the INFORM clinical data bank. Results: Tumour material obtained from brainstem biopsy was sufficient for DNA analysis in all cases and RNA analysis in 16 of 21 cases. In 16 of 21 cases (76%), potential targetable alterations were identified including highly relevant MET and NTRK1 fusions as well as an EZH2 alteration not previously described in DIPG. In 5 of 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 multicentre 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. One of 20 patients experienced unilateral paraesthesia possibly related to biopsy.

FAU Authors / FAU Editors

Metzler, Markus PD Dr.
Professur für Kinder- und Jugendmedizin mit dem Schwerpunkt Pädiatrische Onkologie und Hämatologie

External institutions with authors

Cairo University
Deutsches Herzzentrum Berlin
Frankfurt Cancer Institute
Geneva University Hospitals / Hôpitaux universitaires de Genève (HUG)
Hopp-Kindertumorzentrum Heidelberg - KiTZ
Klinikum Augsburg
Klinikum Stuttgart
Ruprecht-Karls-Universität Heidelberg
Southern Medical University / 南方医科大学
Universität Mannheim
Universitätsklinikum Bonn
Universitätsklinikum Göttingen
Universitätsklinikum Köln
Universitätsklinikum Tübingen

How to cite

Pfaff, E., El Damaty, A., Balasubramanian, G.P., Blattner-Johnson, M., Worst, B.C., Stark, S.,... Witt, O. (2019). Brainstem biopsy in pediatric diffuse intrinsic pontine glioma in the era of precision medicine: the INFORM study experience. European journal of cancer, 114, 27-35.

Pfaff, Elke, et al. "Brainstem biopsy in pediatric diffuse intrinsic pontine glioma in the era of precision medicine: the INFORM study experience." European journal of cancer 114 (2019): 27-35.


Last updated on 2019-14-05 at 01:08

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