Eric Thompson

Overview:

My translational and clinical research focus is pediatric brain tumors. My lab investigates 1) the mechanism of oncolytic viral immunotherapy for the treatment of solid tumor and disseminated medulloblastoma, and 2) the role of Abelson family kinases (ABL1 and ABL2) in the promotion of leptomeningeal dissemination of pediatric brain tumors.

My clinical research focuses on 1) using a novel peptide vaccine to target CMV antigens to treat children with recurrent medulloblastoma and malignant glioma and 2) using oncolytic poliovirus to treat children with recurrent malignant glioma.

Positions:

Associate Professor of Neurosurgery

Neurosurgery
School of Medicine

Associate Professor in Pathology

Pathology
School of Medicine

Assistant Professor in Pediatrics

Pediatrics
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

B.S. 2002

Duke University

M.D. 2006

University of Nebraska, College of Medicine

Neurological Surgery Resident, Neurosurgery

Oregon Health and Science University

Pediatric Neurological Surgery Fellow, Neurosurgery

The Hospital For Sick Children

Grants:

Phase Ib study of Oncolytic Polio/Rhinovirus Recombinant Against Recurrent Malignant Glioma in Children

Administered By
Duke Cancer Institute
Awarded By
Istari Oncology
Role
Principal Investigator
Start Date
End Date

ABL Kinases as Drivers of Medulloblastoma Leptomeningeal Dissemination

Administered By
Neurosurgery
Awarded By
American Society of Pediatric Nephrology
Role
Principal Investigator
Start Date
End Date

Oncolytic Poliovirus Immunotherapy for Pediatric Medulloblastoma

Administered By
Neurosurgery
Awarded By
Musella Foundation For Brain Tumor Research & Information, Inc
Role
Principal Investigator
Start Date
End Date

Phase I study of Oncolytic Polio/Rhinovirus Recombinant Against Recurrent Malignant Glioma in Children

Administered By
Neurosurgery
Awarded By
Musella Foundation For Brain Tumor Research & Information, Inc
Role
Principal Investigator
Start Date
End Date

Optimizing the Convection Enhanced Delivery of Targeted Agents for Midline Gliomas

Administered By
Neurosurgery
Awarded By
Southeastern Brain Tumor Foundation
Role
Principal Investigator
Start Date
End Date

Publications:

Machine Assist for Pediatric Posterior Fossa Tumor Diagnosis: A Multinational Study.

BACKGROUND: Clinicians and machine classifiers reliably diagnose pilocytic astrocytoma (PA) on magnetic resonance imaging (MRI) but less accurately distinguish medulloblastoma (MB) from ependymoma (EP). One strategy is to first rule out the most identifiable diagnosis. OBJECTIVE: To hypothesize a sequential machine-learning classifier could improve diagnostic performance by mimicking a clinician's strategy of excluding PA before distinguishing MB from EP. METHODS: We extracted 1800 total Image Biomarker Standardization Initiative (IBSI)-based features from T2- and gadolinium-enhanced T1-weighted images in a multinational cohort of 274 MB, 156 PA, and 97 EP. We designed a 2-step sequential classifier - first ruling out PA, and next distinguishing MB from EP. For each step, we selected the best performing model from 6-candidate classifier using a reduced feature set, and measured performance on a holdout test set with the microaveraged F1 score. RESULTS: Optimal diagnostic performance was achieved using 2 decision steps, each with its own distinct imaging features and classifier method. A 3-way logistic regression classifier first distinguished PA from non-PA, with T2 uniformity and T1 contrast as the most relevant IBSI features (F1 score 0.8809). A 2-way neural net classifier next distinguished MB from EP, with T2 sphericity and T1 flatness as most relevant (F1 score 0.9189). The combined, sequential classifier was with F1 score 0.9179. CONCLUSION: An MRI-based sequential machine-learning classifiers offer high-performance prediction of pediatric posterior fossa tumors across a large, multinational cohort. Optimization of this model with demographic, clinical, imaging, and molecular predictors could provide significant advantages for family counseling and surgical planning.
Authors
Zhang, M; Wong, SW; Wright, JN; Toescu, S; Mohammadzadeh, M; Han, M; Lummus, S; Wagner, MW; Yecies, D; Lai, H; Eghbal, A; Radmanesh, A; Nemelka, J; Harward, S; Malinzak, M; Laughlin, S; Perreault, S; Braun, KRM; Vossough, A; Poussaint, T; Goetti, R; Ertl-Wagner, B; Ho, CY; Oztekin, O; Ramaswamy, V; Mankad, K; Vitanza, NA; Cheshier, SH; Said, M; Aquilina, K; Thompson, E; Jaju, A; Grant, GA; Lober, RM; Yeom, KW
MLA Citation
Zhang, Michael, et al. “Machine Assist for Pediatric Posterior Fossa Tumor Diagnosis: A Multinational Study.Neurosurgery, vol. 89, no. 5, Oct. 2021, pp. 892–900. Pubmed, doi:10.1093/neuros/nyab311.
URI
https://scholars.duke.edu/individual/pub1494420
PMID
34392363
Source
pubmed
Published In
Neurosurgery
Volume
89
Published Date
Start Page
892
End Page
900
DOI
10.1093/neuros/nyab311

The transcriptional landscape of Shh medulloblastoma.

Sonic hedgehog medulloblastoma encompasses a clinically and molecularly diverse group of cancers of the developing central nervous system. Here, we use unbiased sequencing of the transcriptome across a large cohort of 250 tumors to reveal differences among molecular subtypes of the disease, and demonstrate the previously unappreciated importance of non-coding RNA transcripts. We identify alterations within the cAMP dependent pathway (GNAS, PRKAR1A) which converge on GLI2 activity and show that 18% of tumors have a genetic event that directly targets the abundance and/or stability of MYCN. Furthermore, we discover an extensive network of fusions in focally amplified regions encompassing GLI2, and several loss-of-function fusions in tumor suppressor genes PTCH1, SUFU and NCOR1. Molecular convergence on a subset of genes by nucleotide variants, copy number aberrations, and gene fusions highlight the key roles of specific pathways in the pathogenesis of Sonic hedgehog medulloblastoma and open up opportunities for therapeutic intervention.
Authors
Skowron, P; Farooq, H; Cavalli, FMG; Morrissy, AS; Ly, M; Hendrikse, LD; Wang, EY; Djambazian, H; Zhu, H; Mungall, KL; Trinh, QM; Zheng, T; Dai, S; Stucklin, ASG; Vladoiu, MC; Fong, V; Holgado, BL; Nor, C; Wu, X; Abd-Rabbo, D; Bérubé, P; Wang, YC; Luu, B; Suarez, RA; Rastan, A; Gillmor, AH; Lee, JJY; Zhang, XY; Daniels, C; Dirks, P; Malkin, D; Bouffet, E; Tabori, U; Loukides, J; Doz, FP; Bourdeaut, F; Delattre, OO; Masliah-Planchon, J; Ayrault, O; Kim, S-K; Meyronet, D; Grajkowska, WA; Carlotti, CG; de Torres, C; Mora, J; Eberhart, CG; Van Meir, EG; Kumabe, T; French, PJ; Kros, JM; Jabado, N; Lach, B; Pollack, IF; Hamilton, RL; Rao, AAN; Giannini, C; Olson, JM; Bognár, L; Klekner, A; Zitterbart, K; Phillips, JJ; Thompson, RC; Cooper, MK; Rubin, JB; Liau, LM; Garami, M; Hauser, P; Li, KKW; Ng, H-K; Poon, WS; Yancey Gillespie, G; Chan, JA; Jung, S; McLendon, RE; Thompson, EM; Zagzag, D; Vibhakar, R; Ra, YS; Garre, ML; Schüller, U; Shofuda, T; Faria, CC; López-Aguilar, E; Zadeh, G; Hui, C-C; Ramaswamy, V; Bailey, SD; Jones, SJ; Mungall, AJ; Moore, RA; Calarco, JA; Stein, LD; Bader, GD; Reimand, J; Ragoussis, J; Weiss, WA; Marra, MA; Suzuki, H; Taylor, MD
MLA Citation
Skowron, Patryk, et al. “The transcriptional landscape of Shh medulloblastoma.Nat Commun, vol. 12, no. 1, Mar. 2021, p. 1749. Pubmed, doi:10.1038/s41467-021-21883-0.
URI
https://scholars.duke.edu/individual/pub1476573
PMID
33741928
Source
pubmed
Published In
Nature Communications
Volume
12
Published Date
Start Page
1749
DOI
10.1038/s41467-021-21883-0

Image quality of EOS low-dose radiography in comparison with conventional radiography for assessment of ventriculoperitoneal shunt integrity.

OBJECTIVE: Patients with shunted hydrocephalus often accumulate high levels of radiation over their lifetimes during evaluation of hardware integrity. Current practice involves the use of a series of conventional radiographs for this purpose. Newer low-dose EOS radiography is currently used to evaluate scoliosis but has not been explored to evaluate shunt integrity on a large scale. The goal of this study was to compare the quality of imaging using EOS low-dose radiography to conventional radiography to evaluate shunt tubing. METHODS: A retrospective chart review was performed on 57 patients who previously had both conventional radiographs and low-dose EOS images of their cerebral shunt tubing from 2000 to 2018. Patient demographics (age, sex, type of shunt tubing, primary diagnosis) were collected. Conventional radiographic images and low-dose EOS images were independently analyzed by a neurosurgeon and neuroradiologist in three categories: image quality, delineation of shunt, and distinction of shunt compared to adjacent anatomy. RESULTS: All patients had shunted hydrocephalus due to spina bifida and Chiari type II malformation. Ratings of EOS and conventional radiographic images by both raters did not differ significantly in terms of image quality (rater 1, p = 0.499; rater 2, p = 0.578) or delineation of shunt (p = 0.107 and p = 0.256). Conventional radiographic images received significantly higher ratings than EOS on the ability to distinguish the shunt versus adjacent anatomy by rater 1 (p = 0.039), but not by rater 2 (p = 0.149). The overall score of the three categories combined was not significantly different between EOS and conventional radiography (rater 1, p = 0.818; rater 2, p = 0.186). In terms of cost, an EOS image was less costly than a conventional radiography shunt series ($236-$366 and $1300-$1547, respectively). The radiation dose was also lower for EOS images, with an effective dose of 0.086-0.140 mSv compared to approximately 1.6 mSv for a similar field of view with conventional radiography. CONCLUSIONS: The image quality of low-dose EOS radiography does not significantly differ from conventional radiography for the evaluation of cerebral shunts. In addition, EOS affords a much lower radiation dose and a lower cost.
Authors
Monuszko, K; Malinzak, M; Yang, LZ; Niedzwiecki, D; Fuchs, H; Muh, CR; Gingrich, K; Lark, R; Thompson, EM
MLA Citation
Monuszko, Karen, et al. “Image quality of EOS low-dose radiography in comparison with conventional radiography for assessment of ventriculoperitoneal shunt integrity.J Neurosurg Pediatr, Jan. 2021, pp. 1–7. Pubmed, doi:10.3171/2020.8.PEDS20428.
URI
https://scholars.duke.edu/individual/pub1470934
PMID
33418531
Source
pubmed
Published In
J Neurosurg Pediatr
Published Date
Start Page
1
End Page
7
DOI
10.3171/2020.8.PEDS20428

Perioperative Assessment of Cerebellar Masses and the Potential for Cerebellar Cognitive Affective Syndrome.

The cerebellum was long perceived to be a region of limited importance with primary functions in the regulation of motor control. A degree of its functional topography in motor modulation has been traditionally appreciated. However, an evolving body of evidence supports its role in a range of cognitive processes, including executive decision making, language, emotional processing, and working memory. To this end, numerous studies of cerebellar stroke syndromes as well as investigations with functional magnetic resonance imaging and diffusion tensor imaging have given clinicians a better model of the functional topography within the cerebellum and the essential lanes of communication with the cerebrum. With this deeper understanding, neurosurgeons should integrate these domains into the perioperative evaluation and postoperative rehabilitation of patients with cerebellar tumors. This review aims to discuss these understandings and identify valuable tools for implementation into clinical practice.
Authors
Sankey, EW; Srinivasan, ES; Mehta, VA; Bergin, SM; Wang, TY; Thompson, EM; Fecci, PE; Friedman, AH
MLA Citation
Sankey, Eric W., et al. “Perioperative Assessment of Cerebellar Masses and the Potential for Cerebellar Cognitive Affective Syndrome.World Neurosurg, vol. 144, Dec. 2020, pp. 222–30. Pubmed, doi:10.1016/j.wneu.2020.09.048.
URI
https://scholars.duke.edu/individual/pub1461315
PMID
32949806
Source
pubmed
Published In
World Neurosurg
Volume
144
Published Date
Start Page
222
End Page
230
DOI
10.1016/j.wneu.2020.09.048

Allosteric Inhibition of ABL Kinases: Therapeutic Potential in Cancer.

Tyrosine kinase inhibitors have revolutionized the world of cancer treatment in recent years, profoundly improving survival of patients with chronic myeloid leukemia (CML) and beyond. However, off-target toxicities of these inhibitors are well-described, and resistance has become a paramount concern. Novel allosteric inhibitors of the Abelson (ABL) family of tyrosine kinases, including GNF-2, GNF-5, and ABL-001, are equipped to overcome these issues. Several contemporary studies have demonstrated their potential efficacy in three key areas: primary hematologic and solid malignancies, metastasis, and combination with other small molecules. Further, ongoing clinical trials are investigating the efficacy of ABL-001 for the treatment of CML and recurrent solid tumors. This work reviews the current literature of the preclinical testing of GNF-2 and GNF-5 and the preclinical and clinical testing of ABL-001. Future research will continue to evaluate these promising inhibitors as both first-line therapy for solid tumors and salvage therapy when more traditional drugs such as imatinib fail.
Authors
Jones, JK; Thompson, EM
MLA Citation
Jones, Jill K., and Eric M. Thompson. “Allosteric Inhibition of ABL Kinases: Therapeutic Potential in Cancer.Mol Cancer Ther, vol. 19, no. 9, Sept. 2020, pp. 1763–69. Pubmed, doi:10.1158/1535-7163.MCT-20-0069.
URI
https://scholars.duke.edu/individual/pub1474635
PMID
32606014
Source
pubmed
Published In
Mol Cancer Ther
Volume
19
Published Date
Start Page
1763
End Page
1769
DOI
10.1158/1535-7163.MCT-20-0069

Research Areas:

Brain Neoplasms
Neoplasm Metastasis
Neoplasm Proteins
Neoplasm Recurrence, Local
Neoplasms, Experimental
Neoplasms, Nerve Tissue
Spine--Abnormalities--Surgery