Contrast enhancing spots as a new pattern of late onset pseudoprogression in glioma patients

  • Martin VossEmail author
  • Kea Franz
  • Joachim P. Steinbach
  • Emmanouil Fokas
  • Marie-Thérèse Forster
  • Katharina Filipski
  • Elke Hattingen
  • Marlies Wagner
  • Stella Breuer
Clinical Study



Magnet resonance imaging (MRI) of gliomas is assessed by Response Assessment in Neuro-Oncology Criteria (RANO), which define new contrast-enhancing lesions as a sign for tumor recurrence. Pseudoprogression after radiotherapy may mimic tumor progression in MRI but is usually limited to the first months after irradiation. We noted a late onset pattern of new contrast-enhancing spots (NCES) appearing years after radiotherapy.


We prospectively collected 23 glioma patients with 26 NCES (three patients had two separate NCES events) between 2014 and 2016 in our weekly tumor board without further selection by diagnosis, molecular markers or pretreatment.


Retrospective analysis revealed a homogeneous collective of young patients (median age of 49 years at NCES) with mainly IDH-mutated glioma (61%). Initial histology showed 26% glioblastoma, 52% grade III and 22% grade II glioma. NCES occurred at late follow-up with a median of 52 months after tumor diagnosis and 30 months after the last radiotherapy. The majority of NCES regressed spontaneously within a median of 10 months (n = 11) or remained stable without further therapy with a median follow-up of 26 months (n = 7). Only 4 NCES developed MRI morphologically into tumor recurrence. Two NCES were resected without any histopathological proof of tumor recurrence, and in 2 other cases NCES were defined as ischemic stroke or radionecrosis.


We hypothesize that the late onset phenomenon of NCES predominantly represents a form of radiation-induced vasculopathy that is different from early pseudoprogression and should be considered especially in younger patients with IDH-mutated glioma before initiation of new therapy.


Pseudoprogression Radionecrosis Glioma Brain tumor Isocitrat dehydrogenase (IDH) 



The Senckenberg Institute of Neurooncology is supported by the Senckenberg Foundation.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

This study has been accepted by the local ethics committee (SNO_SNO_01–08).

Supplementary material

11060_2018_3076_MOESM1_ESM.docx (16 kb)
Supplementary material 1 (DOCX 16 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Martin Voss
    • 1
    Email author
  • Kea Franz
    • 2
  • Joachim P. Steinbach
    • 1
  • Emmanouil Fokas
    • 3
  • Marie-Thérèse Forster
    • 2
  • Katharina Filipski
    • 4
  • Elke Hattingen
    • 5
  • Marlies Wagner
    • 5
  • Stella Breuer
    • 5
  1. 1.Dr. Senckenberg Institute of NeurooncologyUniversity Hospital Frankfurt, Goethe UniversityFrankfurt am MainGermany
  2. 2.Departement of NeurosurgeryUniversity Hospital Frankfurt, Goethe UniversityFrankfurt am MainGermany
  3. 3.Department of Radiotherapy and OncologyUniversity Hospital Frankfurt, Goethe UniversityFrankfurt am MainGermany
  4. 4.Institut of Neurology (Edinger-Institute)University Hospital Frankfurt, Goethe UniversityFrankfurt am MainGermany
  5. 5.Departement of NeuroradiologyUniversity Hospital Frankfurt, Goethe UniversityFrankfurt am MainGermany

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