IMR Press / FBL / Volume 27 / Issue 7 / DOI: 10.31083/j.fbl2707219
Open Access Original Research
The “SEED” Study: The Feasibility of Selecting Patient-Specific Biologically Targeted Therapy with Sorafenib, Everolimus, Erlotinib or Dasatinib for Pediatric and Young Adult Patients with Recurrent or Refractory Brain Tumors
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1 Department of Laboratories, Seattle Children’s Hospital, Seattle, WA 98105, USA
2 Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA 98195, USA
3 Ben Towne Center for Childhood Cancer Research, Seattle Children’s Research Institute, Seattle, WA 98105, USA
4 Department of Pediatrics, University of Washington, Seattle, WA 98195, USA
*Correspondence: (Bonnie Cole); (Sarah E. S. Leary)
Academic Editors: Yingqun Wang, Haihua Feng and Graham Pawelec
Front. Biosci. (Landmark Ed) 2022, 27(7), 219;
Submitted: 29 December 2021 | Revised: 8 February 2022 | Accepted: 3 March 2022 | Published: 12 July 2022
(This article belongs to the Special Issue Novel Approaches to Cancer Diagnosis and Therapy)
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Background: Pediatric brain tumors are the leading cause of cancer death in children and represent a variety of diseases and molecular subtypes. This study sought to evaluate a rapid immunohistochemistry testing panel to aid in therapy selection at the time of malignant tumor recurrence. Methods: With IRB approval and appropriate informed consent, we conducted a single-institution prospective clinical trial of selected kinase inhibitor therapy. A laboratory-developed immunohistochemical testing panel was performed on tumor tissue, and therapy with one of four small molecule inhibitors was recommended in combination with oral chemotherapy consisting of temozolomide and etoposide. Results: All 20 enrolled subjects were assigned to Everolimus (n = 4), Erlotinib (n = 6) or Dasatinib (n = 10); 90% (18/20) within the pre-specified 14-day feasibility time period. Only two subjects elected treatment on study, 8 received targeted treatment based on testing results either alone (n = 5) or in combination with chemotherapy (n = 3). Other subjects received chemotherapy alone (n = 7), surgery alone (n = 2) or no further therapy (n = 3). Immunohistochemical targets were associated with correlative genetic changes in 28% (5/18) of those evaluated. Conclusions: It was feasible to rapidly select targeted therapy in recurrent pediatric brain tumors, but not feasible to treat with a uniform combination treatment regimen.

brain tumor
clinical trial
Fig. 1.
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