The pivotal role of sampling recurrent tumors in the precision care of patients with tumors of the central nervous system

Abstract

Effective management of brain and spine tumors relies on a multidisciplinary approach encompassing surgery, radiation, and systemic therapy. In the era of personalized oncology, the latter is complemented by various molecularly targeting agents. Precise identification of cellular targets for these drugs requires comprehensive profiling of the cancer genome coupled with an efficient analytic pipeline, leading to an informed decision on drug selection, prognosis, and confirmation of the original pathological diagnosis. Acquisition of optimal tumor tissue for such analysis is paramount and often presents logistical challenges in neurosurgery. Here, we describe the experience and results of the Personalized OncoGenomics (POG) program with a focus on tumors of the central nervous system (CNS). Patients with recurrent CNS tumors were consented and enrolled into the POG program prior to accrual of tumor and matched blood followed by whole-genome and transcriptome sequencing and processing through the POG bioinformatic pipeline. Sixteen patients were enrolled into POG. In each case, POG analyses identified genomic drivers including novel oncogenic fusions, aberrant pathways, and putative therapeutic targets. POG has highlighted that personalized oncology is truly a multidisciplinary field, one in which neurosurgeons must play a vital role if these programs are to succeed and benefit our patients.

Trial registration: ClinicalTrials.gov NCT02155621.

Keywords: neoplasm of the central nervous system; neoplasm of the peripheral nervous system.

© 2019 Wong et al.; Published by Cold Spring Harbor Laboratory Press.

Figures

Figure 1.

Patient demographics. Pie charts showing the distribution of sex, tumor origin, tumor location (intra- vs. extra-axial), tumor location (brain hemisphere), tumor type, and tumor grade and a bar chart showing the frequency of age at diagnosis for all POG patients.

Figure 2.

(A) Stacked bar chart showing total number of protein-coding single-nucleotide variants and truncating single-nucleotide variants identified in each POG case. (B) Stacked bar chart showing total number of insertion/deletion events and frameshift insertion/deletion events identified in each POG case. (C) Stacked bar chart showing the total number of structural variants and expressed fusion transcripts identified in each POG case. (D) (Left) Stacked bar chart comparing the total number of protein-coding single-nucleotide variants and truncating single-nucleotide variants identified in archived FFPE and fresh tumor in ODG1 and ODG2, both oligodendrogliomas. (Right) Stacked bar chart comparing the total number of insertion/deletions and frameshift insertion/deletions identified in archived FFPE and fresh tumor in ODG1 and ODG2, both oligodendrogliomas.

Figure 3.

Extra-axial collage showing MRI scans, histology, and a genomic finding of interest for select cases. Cases are presented from top to bottom as follows: (CHD1) chordoma (high FOS/JUN expression), (CHD2) chordoma (high T and MET expression), (MGM1) orbital meningioma (MN1-CXXC5 fusion), (MGM2) meningioma (NF2 loss), (MPE1) anaplastic myxopapillary ependymoma (NF2 loss).

Figure 4.

Intra-axial collage showing MRI scans, histology, and a genomic finding of interest for select cases. Cases are presented from top to bottom as follows: (ODG1) oligodendroglioma (1p19q co-deletion in primary and recurrent tissue), (GBM1) IDH mutated recurrent glioblastoma (PI3KCA-activating missense mutation), (EPN1) supratentorial ependymoma (EWSR1-PATZ1 fusion), (EPN2) ependymoma (RELA fusion), (PXA1) pleomorphic xanthoastrocytoma (high PDL1 expression).