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J Neurooncol. 2016 Oct;130(1):211-219. Epub 2016 Aug 16.

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

Author information

  • 1Division of Oncology, Neuro-Oncology Service, Tel Aviv Sourasky Medical Center, 6 Weizman Street, 64239, Tel Aviv, Israel. deborahblumenthal@gmail.com.
  • 2Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. deborahblumenthal@gmail.com.
  • 3Oncotest-Teva Pharmaceuticals, Petah Tikva, Israel.
  • 4Department of Oncology, Leslie and Michael Gaffin Center for Neuro-Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
  • 5Department of Oncology, Rambam Health Care Campus, Haifa, Israel.
  • 6Oncology Institute, Chaim Sheba Medical Center, Tel Hashomer, Israel.
  • 7Oncology Institute, Davidoff Center, Rabin Medical Center, Petah Tikva, Israel.
  • 8Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • 9Department of Neurosurgery, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
  • 10Foundation Medicine, Cambridge, MA, USA.
  • 11Albany Medical College, Albany, NY, USA.
  • 12Division of Oncology, Neuro-Oncology Service, Tel Aviv Sourasky Medical Center, 6 Weizman Street, 64239, Tel Aviv, Israel.

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.

KEYWORDS:

Astrocytoma; Glioblastoma; High grade glioma; Massively-parallel sequencing; Targeted molecular therapy

PMID:
27531351
DOI:
10.1007/s11060-016-2237-3
[PubMed - in process]
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