title: Pediatric Targeted Therapy: Clinical Feasibility of Personalized Diagnostics in Children with Relapsed and Progressive Tumors.
abstract: The "pediatric targeted therapy" (PTT) program aims to identify the presence and activity of druggable targets and evaluate the clinical benefit of a personalized treatment approach in relapsed or progressive tumors on an individual basis. 10 markers (HDAC2, HR23B, p-AKT, p-ERK, p-S6, p-EGFR, PDGFR-alpha/beta, p53 and BRAFV600E) were analyzed by immunohistochemistry. Pediatric patients with tumors independent of the histological diagnosis, with relapse or progression after treatment according to standard protocols were included. N = 61/145 (42%) cases were eligible for analysis between 2009 and 2013, the most common entities being brain tumors. Immunohistochemical stainings were evaluated by the H-Score (0-300). In 93% of the cases potentially actionable targets were identified. The expressed or activated pathways were histone deacetylase (HDACs; 83.0% of cases positive), EGFR (87.2%), PDGFR (75.9%), p53 (50.0%), MAPK/ERK (43.3%) and PI3K/mTOR (36.1%). Follow-up revealed partial or full implementation of PTT results in treatment decision-making in 41% of the cases. Prolonged disease stabilization responses in single cases were noticed, however, response rates did not differ from cases treated with other modalities. Further studies evaluating the feasibility and clinical benefit of personalized diagnostic approaches using paraffin material are warranted.
authors.affiliation: Clinical Cooperation Unit Pediatric Oncology (G340), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.|Department of Pediatric Oncology, Hematology and Immunology, Section of Pediatric Brain Tumors, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.|National Center for Tumor diseases (NCT), Clinical Trial Center, Im Neuenheimer Feld 350, 69120 Heidelberg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Selt
authors.affiliation: Clinical Cooperation Unit Pediatric Oncology (G340), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
authors.forename: Alica
authors.initials: A
authors.lastname: Deiß
authors.affiliation: Department of Neuropathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany.|Clinical Cooperation Unit Neuropathology (G380), German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Heidelberg.
authors.forename: Andrey
authors.initials: A
authors.lastname: Korshunov
authors.affiliation: Department of Neuropathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany.|Clinical Cooperation Unit Neuropathology (G380), German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Heidelberg.
authors.forename: David
authors.initials: D
authors.lastname: Capper
authors.affiliation: Department of Pediatric Oncology, Hematology and Immunology, Section of Pediatric Brain Tumors, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.|Division of Pediatric Neurooncology (B062), German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Heidelberg.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Witt
authors.affiliation: Department of Pediatric Oncology, Hematology and Immunology, Section of Pediatric Brain Tumors, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.|National Center for Tumor diseases (NCT), Clinical Trial Center, Im Neuenheimer Feld 350, 69120 Heidelberg, Germany.
authors.forename: Cornelis M
authors.initials: CM
authors.lastname: van Tilburg
authors.affiliation: Division of Pediatric Neurooncology (B062), German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Heidelberg.
authors.forename: David T W
authors.initials: DT
authors.lastname: Jones
authors.affiliation: Clinical Cooperation Unit Pediatric Oncology (G340), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.|Department of Pediatric Oncology, Hematology and Immunology, Section of Pediatric Brain Tumors, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.|National Center for Tumor diseases (NCT), Clinical Trial Center, Im Neuenheimer Feld 350, 69120 Heidelberg, Germany.
authors.forename: Ruth
authors.initials: R
authors.lastname: Witt
authors.affiliation: Department of Neuropathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany.|Clinical Cooperation Unit Neuropathology (G380), German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Heidelberg.
authors.forename: Felix
authors.initials: F
authors.lastname: Sahm
authors.affiliation: Department of Neuropathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany.|Clinical Cooperation Unit Neuropathology (G380), German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Heidelberg.
authors.forename: David
authors.initials: D
authors.lastname: Reuss
authors.affiliation: Department of Neuropathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany.|Clinical Cooperation Unit Neuropathology (G380), German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Heidelberg.
authors.forename: Christian
authors.initials: C
authors.lastname: Kölsche
authors.affiliation: Clinical Cooperation Unit Pediatric Oncology (G340), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
authors.forename: Jonas
authors.initials: J
authors.lastname: Ecker
authors.affiliation: Clinical Cooperation Unit Pediatric Oncology (G340), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Oehme
authors.affiliation: Division of Biostatistics (C060), German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hielscher
authors.affiliation: Department of Neuropathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany.|Clinical Cooperation Unit Neuropathology (G380), German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Heidelberg.
authors.forename: Andreas
authors.initials: A
authors.lastname: von Deimling
authors.affiliation: Department of Pediatric Oncology, Hematology and Immunology, Section of Pediatric Brain Tumors, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.
authors.forename: Andreas E
authors.initials: AE
authors.lastname: Kulozik
authors.affiliation: Department of Pediatric Oncology, Hematology and Immunology, Section of Pediatric Brain Tumors, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.|Division of Pediatric Neurooncology (B062), German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Heidelberg.|National Center for Tumor diseases (NCT), Clinical Trial Center, Im Neuenheimer Feld 350, 69120 Heidelberg, Germany.
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Pfister
authors.affiliation: Clinical Cooperation Unit Pediatric Oncology (G340), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.|Department of Pediatric Oncology, Hematology and Immunology, Section of Pediatric Brain Tumors, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.|National Center for Tumor diseases (NCT), Clinical Trial Center, Im Neuenheimer Feld 350, 69120 Heidelberg, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Witt
authors.affiliation: Clinical Cooperation Unit Pediatric Oncology (G340), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.|Department of Pediatric Oncology, Hematology and Immunology, Section of Pediatric Brain Tumors, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.|National Center for Tumor diseases (NCT), Clinical Trial Center, Im Neuenheimer Feld 350, 69120 Heidelberg, Germany.
authors.forename: Till
authors.initials: T
authors.lastname: Milde
mesh_terms: D000293:Adolescent; D014408:Biomarkers, Tumor / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D058990:Molecular Targeted Therapy / Q000379:methods*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009369:Neoplasms / Q000188:drug therapy*; D057285:Precision Medicine / Q000379:methods*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor
keywords: brain tumors; pediatric oncology; personalized medicine; predictive markers; relapsed childhood tumors; targeted therapy