Details

Autor(en) / Beteiligte

• Worst, Barbara C
• van Tilburg, Cornelis M
• Balasubramanian, Gnana Prakash
• Fiesel, Petra
• Witt, Ruth
• Freitag, Angelika
• Boudalil, Miream
• Previti, Christopher
• Wolf, Stephan
• Schmidt, Sabine
• Chotewutmontri, Sasithorn
• Bewerunge-Hudler, Melanie
• Schick, Matthias
• Schlesner, Matthias
• Hutter, Barbara
• Taylor, Lenka
• Borst, Tobias
• Sutter, Christian
• Bartram, Claus R
• Milde, Till
• Pfaff, Elke
• Kulozik, Andreas E
• von Stackelberg, Arend
• Meisel, Roland
• Borkhardt, Arndt
• Reinhardt, Dirk
• Klusmann, Jan-Henning
• Fleischhack, Gudrun
• Tippelt, Stephan
• Dirksen, Uta
• Jürgens, Heribert
• Kramm, Christof M
• von Bueren, Andre O
• Westermann, Frank
• Fischer, Matthias
• Burkhardt, Birgit
• Wößmann, Wilhelm
• Nathrath, Michaela
• Bielack, Stefan S
• Frühwald, Michael C
• Fulda, Simone
• Klingebiel, Thomas
• Koscielniak, Ewa
• Schwab, Matthias
• Tremmel, Roman
• Driever, Pablo Hernáiz
• Schulte, Johannes H
• Brors, Benedikt
• von Deimling, Andreas
• Lichter, Peter
• Eggert, Angelika
• Capper, David
• Pfister, Stefan M
• Jones, David T.W
• Witt, Olaf

Titel

Next-generation personalised medicine for high-risk paediatric cancer patients – The INFORM pilot study

Ist Teil von

• European journal of cancer (1990), 2016-09, Vol.65, p.91-101

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2016

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Abstract The ‘Individualized Therapy for Relapsed Malignancies in Childhood’ (INFORM) precision medicine study is a nationwide German program for children with high-risk relapsed/refractory malignancies, which aims to identify therapeutic targets on an individualised basis. In a pilot phase, reported here, we developed the logistical and analytical pipelines necessary for rapid and comprehensive molecular profiling in a clinical setting. Fifty-seven patients from 20 centers were prospectively recruited. Malignancies investigated included sarcomas (n = 25), brain tumours (n = 23), and others (n = 9). Whole-exome, low-coverage whole-genome, and RNA sequencing were complemented with methylation and expression microarray analyses. Alterations were assessed for potential targetability according to a customised prioritisation algorithm and subsequently discussed in an interdisciplinary molecular tumour board. Next-generation sequencing data were generated for 52 patients, with the full analysis possible in 46 of 52. Turnaround time from sample receipt until first report averaged 28 d. Twenty-six patients (50%) harbored a potentially druggable alteration with a prioritisation score of ‘intermediate’ or higher (level 4 of 7). Common targets included receptor tyrosine kinases, phosphoinositide 3-kinase–mammalian target of rapamycin pathway, mitogen-activated protein kinase pathway, and cell cycle control. Ten patients received a targeted therapy based on these findings, with responses observed in some previously treatment-refractory tumours. Comparative primary relapse analysis revealed substantial tumour evolution as well as one case of unsuspected secondary malignancy, highlighting the importance of re-biopsy at relapse. This study demonstrates the feasibility of comprehensive, real-time molecular profiling for high-risk paediatric cancer patients. This extended proof-of-concept, with examples of treatment consequences, expands upon previous personalised oncology endeavors, and presents a model with considerable interest and practical relevance in the burgeoning era of personalised medicine.