Brainstem biopsy in pediatric diffuse intrinsic pontine glioma in the era of precision medicine: the INFORM study experience. (June 2019)

• Record Type: Journal Article
• Authors: 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;
• Is Part Of: European journal of cancer. Volume 114(2019)
• Page Start: 27
• Page End: 35
• Publication Date: 2019-06
• Subjects: Pediatric diffuse intrinsic pons glioma -- Brainstem biopsy -- Molecular profiling -- Targeted therapy; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2019.03.019
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: 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. Highlights: 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.