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Journal of Neuro-Oncology

, Volume 130, Issue 3, pp 529–533 | Cite as

Molecular and histologic characteristics of pseudoprogression in diffuse gliomas

  • Andrew L. Lin
  • Michael White
  • Michelle M. Miller-Thomas
  • Robert S. Fulton
  • Christina I. Tsien
  • Keith M. Rich
  • Robert E. Schmidt
  • David D. Tran
  • Sonika Dahiya
Clinical Study

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.

Keywords

Diffuse glioma Oligodendroglioma Mixed oligoastrocytoma Astrocytoma Pseudoprogression Radiation necrosis 

Notes

Acknowledgments

The authors would like to thank David Carrell and Lisa Snipes at Washington University School of Medicine for their technical assistance.

Funding

This work was supported by Washington University Institute of Clinical and Translational Services, which is in part supported by the NIH/National Center for Advancing Translational Sciences (NCATS), CTSA Grant UL1TR0004489 (ICTS JIT # 312 awarded to S.D.).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required. This article does not contain any studies with animals performed by any of the authors.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Andrew L. Lin
    • 1
    • 8
  • Michael White
    • 1
  • Michelle M. Miller-Thomas
    • 2
  • Robert S. Fulton
    • 3
  • Christina I. Tsien
    • 4
  • Keith M. Rich
    • 5
  • Robert E. Schmidt
    • 6
  • David D. Tran
    • 7
    • 9
  • Sonika Dahiya
    • 6
  1. 1.Department of NeurologyWashington University School of Medicine in St. LouisSt. LouisUSA
  2. 2.Mallinckrodt Institute of RadiologyWashington University School of Medicine in St. LouisSt. LouisUSA
  3. 3.McDonnell Genome InstituteWashington University School of Medicine in St. LouisSt. LouisUSA
  4. 4.Department of Radiation OncologyWashington University School of Medicine in St. LouisSt. LouisUSA
  5. 5.Department of NeurosurgeryWashington University School of Medicine in St. LouisSt. LouisUSA
  6. 6.Department of Pathology and ImmunologyWashington University School of Medicine in St. LouisSt. LouisUSA
  7. 7.Neuro-Oncology Program, Department of Internal MedicineWashington University School of Medicine in St. LouisSt. LouisUSA
  8. 8.Department of NeurologyMemorial Sloan Kettering Cancer CenterNew YorkUSA
  9. 9.Division of Neuro-Oncology, Department of NeurosurgeryUniversity of FloridaGainesvilleUSA

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