title: Molecular and histologic characteristics of pseudoprogression in diffuse gliomas.
abstract: During the 6 month period following chemoradiotherapy, gliomas frequently develop new areas of contrast enhancement, which are due to treatment effect rather than tumor progression. We sought to characterize this phenomenon in oligodendrogliomas (OG) and mixed oligoastrocytomas (MOA). We reviewed the imaging findings from 143 patients with a WHO grade II or III OG or MOA for evidence of pseudoprogression (PsP) or early tumor progression. We characterized these cases for 1p/19q codeletions by FISH, IDH1 R132H mutation by immunohistochemistry, and TP53, ATRX, and EGFR mutations by next generation sequencing. We then reviewed the pathologic specimens of the patient cases in which a re-resection was performed. We found that OG and MOA that are 1p/19q intact developed PsP at a higher rate than tumors that are 1p/19q codeleted (27 vs. 8 %). Moreover, IDH1 wild-type (WT) tumors developed PsP at a higher rate than IDH1 R132H cases (27 vs. 11 %). Patients with ATRX or TP53 mutations developed PsP at an intermediate rate of 21 %. Ten patients in our cohort underwent a re-resection for early contrast enhancement; these tumors were predominantly 1p/19q intact (90 %) and had a low rate of IDH1 R132H mutation (50 %). 8 of 10 tumors demonstrated primarily treatment effects, while the remaining 2 of 10 demonstrated recurrent/residual tumor of the same grade. Early contrast enhancement that develops during the first 6 months after chemoradiotherapy is typically due to PsP and occurs primarily in OG and MOA that are 1p/19q intact and IDH WT.
authors.affiliation: Department of Neurology, Washington University School of Medicine in St. Louis, 660 S Euclid Ave, St. Louis, MO, 63110, USA.|Department of Neurology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Lin
authors.affiliation: Department of Neurology, Washington University School of Medicine in St. Louis, 660 S Euclid Ave, St. Louis, MO, 63110, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: White
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, 660 S Euclid Ave, St. Louis, MO, 63110, USA.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Miller-Thomas
authors.affiliation: McDonnell Genome Institute, Washington University School of Medicine in St. Louis, 660 S Euclid Ave, St. Louis, MO, 63110, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Fulton
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine in St. Louis, 660 S Euclid Ave, St. Louis, MO, 63110, USA.
authors.forename: Christina I
authors.initials: CI
authors.lastname: Tsien
authors.affiliation: Department of Neurosurgery, Washington University School of Medicine in St. Louis, 660 S Euclid Ave, St. Louis, MO, 63110, USA.
authors.forename: Keith M
authors.initials: KM
authors.lastname: Rich
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, 660 S Euclid Ave, St. Louis, MO, 63110, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Schmidt
authors.affiliation: Neuro-Oncology Program, Department of Internal Medicine, Washington University School of Medicine in St. Louis, 660 S Euclid Ave, St. Louis, MO, 63110, USA. david.tran@neurosurgery.ufl.edu.|Division of Neuro-Oncology, Department of Neurosurgery, University of Florida, 1149 S Newell Drive, Suite L2-100, Gainesville, FL, 32611, USA. david.tran@neurosurgery.ufl.edu.
authors.forename: David D
authors.initials: DD
authors.lastname: Tran
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, 660 S Euclid Ave, St. Louis, MO, 63110, USA. sdahiya@path.wustl.edu.
authors.forename: Sonika
authors.initials: S
authors.lastname: Dahiya
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology*; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005910:Glioma / Q000235:genetics* / Q000473:pathology*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D008297:Male; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D000075924:X-linked Nuclear Protein / Q000235:genetics
chemical_list: D009363:Neoplasm Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein
keywords: Astrocytoma; Diffuse glioma; Mixed oligoastrocytoma; Oligodendroglioma; Pseudoprogression; Radiation necrosis