Details

Autor(en) / Beteiligte

• Pfaff, Elke
• El Damaty, Ahmed
• Balasubramanian, Gnana Prakash
• Blattner-Johnson, Mirjam
• Worst, Barbara C.
• Stark, Sebastian
• Witt, Hendrik
• Pajtler, Kristian W.
• van Tilburg, Cornelis M.
• Witt, Ruth
• Milde, Till
• Jakobs, Martin
• Fiesel, Petra
• Frühwald, Michael C.
• Hernáiz Driever, Pablo
• Thomale, Ulrich W.
• Schuhmann, Martin U.
• Metzler, Markus
• Bochennek, Konrad
• Simon, Thorsten
• Dürken, Matthias
• Karremann, Michael
• Knirsch, Stephanie
• Ebinger, Martin
• von Bueren, André O.
• Pietsch, Torsten
• Herold-Mende, Christel
• Reuss, David E.
• Kiening, Karl
• Lichter, Peter
• Eggert, Angelika
• Kramm, Christof M.
• Pfister, Stefan M.
• Jones, David T.W.
• Bächli, Heidi
• Witt, Olaf

Titel

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

Ist Teil von

• European journal of cancer (1990), 2019-06, Vol.114, p.27-35

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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. 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. 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. •Brainstem biopsies of DIPG are relatively safe in a ‘real life’ setting involving multiple centres.•Full range of state-of-the-art molecular characterisation is feasible in a rapid turnaround time.•Actionable targets are identified in the majority of cases with clinical impact in some cases.