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Author Notes:

Surabhi Ranjan, Email: surabhi.ranjan@nih.gov

SR, MRG, JW conceived the design, analyzed and interpreted the data, drafted and critically revised the manuscript for intellectual content.

MQ and OLAN performed the pathological diagnosis on all patients and drafted the manuscript.

NG, LB, CS, BJT, DMP, EN and KAZ contributed to the acquisition, analysis and interpretation of data and revised the manuscript for intellectual content.

All authors read and approved the final manuscript.

The authors declare that that they have no competing interests.


Research Funding:

This project has been fully funded by the Intramural Research Program of the National Institutes of Health. LB & CS: This project has been funded in whole with federal funds from the National Cancer Institute, National Institutes of Health (NIH), under Contract No. HHSN261200800001E.

BJT: The identification of specific products or scientific instrumentation is considered an integral part of the scientific endeavor and does not constitute endorsement or implied endorsement on the part of the author, DoD, or any component agency.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Oncology
  • CTLA-4
  • Immune checkpoint inhibitors
  • Immunotherapy
  • Ipilimumab
  • iRANO
  • PD-1
  • Pseudoprogression
  • Nivolumab

Clinical decision making in the era of immunotherapy for high grade-glioma: report of four cases

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Journal Title:

BMC Cancer


Volume 18, Number 1


, Pages 239-239

Type of Work:

Article | Final Publisher PDF


Background: Immune checkpoint inhibitors (ICPIs) are being investigated in clinical trials for patients with glioblastoma. While these therapies hold great promise, management of the patients receiving such treatment can be complicated due to thechallenges in recognizing immune-related adverse events caused by checkpoint inhibitor treatment. Brain imaging changes that are the consequence of an inflammatory response may be misinterpreted as disease progression leading to inappropriate premature cessation of treatment. The aim of this study was to, by way of a series of cases, underscore the challenges in determining the nature of contrast-enhancing masses that develop during the treatment of patients with glioblastoma treated with ICPIs. Case presentation: We reviewed the clinical course and management of 4 patients on ICPIs who developed signs of tumor progression on imaging. These findings were examined in the context of Immunotherapy Response Assessment in Neuro-Oncology (iRANO) guidelines. Although all 4 patients had very similar imaging findings, 2 of the 4 patients were later found to have intense inflammatory changes (pseudoprogression) by pathologic examination. Conclusions: A high index of suspicion for pseudoprogression needs to be maintained when a patient with brain tumor on immunotherapy presents with worsening in an area of a pre-existing tumor or a new lesion in brain. Our findings strongly suggest that pathological diagnosis remains the gold standard for distinguishing tumor progression from pseudoprogression in patients receiving immunotherapy. There is a large unmet need to develop reliable non-invasive imaging diagnostic techniques.

Copyright information:

© 2018 The Author(s).

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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