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Journal of Neuro-Oncology
Published in: Journal of Neuro-Oncology 1/2016

01-10-2016 | Clinical Study

Clinical utility and treatment outcome of comprehensive genomic profiling in high grade glioma patients

Authors: Deborah T. Blumenthal, Addie Dvir, Alexander Lossos, Tzahala Tzuk-Shina, Tzach Lior, Dror Limon, Shlomit Yust-Katz, Alejandro Lokiec, Zvi Ram, Jeffrey S. Ross, Siraj M. Ali, Roi Yair, Lior Soussan-Gutman, Felix Bokstein

Published in: Journal of Neuro-Oncology | Issue 1/2016

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Abstract

Genomic research of high grade glioma (HGG) has revealed complex biology with potential for therapeutic impact. However, the utilization of this information and impact upon patient outcome has yet to be assessed. We performed capture-based next generation sequencing (NGS) genomic analysis assay of 236/315 cancer-associated genes, with average depth of over 1000 fold, to guide treatment in HGG patients. We reviewed clinical utility and response rates in correlation to NGS results. Forty-three patients were profiled: 34 glioblastomas, 8 anaplastic astrocytomas, and one patient with anaplastic oligodendroglioma. Twenty-five patients were profiled with the 315 gene panel. The median number of identified genomic alterations (GAs) per patient was 4.5 (range 1–23). In 41 patients (95 %) at least one therapeutically-actionable GA was detected, most commonly in EGFR [17 (40 %)]. Genotype-directed treatments were prescribed in 13 patients, representing a 30 % treatment decision impact. Treatment with targeted agents included everolimus as a single agent and in combination with erlotinib; erlotinib; afatinib; palbociclib; trametinib and BGJ398. Treatments targeted various genomic findings including EGFR alterations, mTOR activation, cell cycle targets and FGFR1 mutations. None of the patients showed response to respective biologic treatments. In this group of patients with HGG, NGS revealed a high frequency of GAs that lead to targeted treatment in 30 % of the patients. The lack of response suggests that further study of mechanisms of resistance in HGG is warranted before routine use of biologically-targeted agents based on NGS results.
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Metadata
Title
Clinical utility and treatment outcome of comprehensive genomic profiling in high grade glioma patients
Authors
Deborah T. Blumenthal
Addie Dvir
Alexander Lossos
Tzahala Tzuk-Shina
Tzach Lior
Dror Limon
Shlomit Yust-Katz
Alejandro Lokiec
Zvi Ram
Jeffrey S. Ross
Siraj M. Ali
Roi Yair
Lior Soussan-Gutman
Felix Bokstein
Publication date
01-10-2016
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 1/2016
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-016-2237-3

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