Brainstem biopsy in pediatric diffuse intrinsic pontine glioma in the era of precision medicine: the INFORM study experience
| Autor: | Stephanie Knirsch, Till Milde, Michael C. Frühwald, Martin Jakobs, Martin U. Schuhmann, Peter Lichter, Michael Karremann, Angelika Eggert, Cornelis M. van Tilburg, Christof M. Kramm, Hendrik Witt, Karl L. Kiening, David T.W. Jones, Ruth Witt, Konrad Bochennek, Mirjam Blattner-Johnson, Sebastian Stark, Martin Ebinger, Heidi Bächli, Pablo Hernáiz Driever, Markus Metzler, André O. von Bueren, Christel Herold-Mende, Elke Pfaff, Ulrich W. Thomale, Torsten Pietsch, Olaf Witt, Kristian W. Pajtler, Stefan M. Pfister, David E. Reuss, Petra Fiesel, Barbara C. Worst, Matthias Dürken, Thorsten Simon, Ahmed El Damaty, Gnana Prakash Balasubramanian |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Cancer Research medicine.medical_specialty Fatal outcome Adolescent Registry study medicine.medical_treatment Biopsy Newly diagnosed Targeted therapy 03 medical and health sciences Molecular profiling 0302 clinical medicine RNA analysis Pediatric diffuse intrinsic pons glioma medicine Brain Stem Neoplasms Humans Prospective Studies Precision Medicine Brainstem biopsy Child ddc:618 medicine.diagnostic_test business.industry Glioma Brain Stem Neoplasms / surgery Precision medicine 3. Good health Glioma / surgery 030104 developmental biology Oncology Biopsy / methods 030220 oncology & carcinogenesis Child Preschool Female Radiology Brainstem business |
| Zdroj: | European journal of cancer, Vol. 114 (2019) pp. 27-35 |
| ISSN: | 1879-0852 0959-8049 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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